A Study to Assess the Effect of Tocilizumab + Methotrexate on Prevention of Structural Joint Damage in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT00106535

Collaborator

(none)

1,196

Enrollment

152

Locations

Arms

Duration (Months)

7.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This 3 arm study will compare the safety and efficacy, with respect to a reduction in signs and symptoms and prevention of joint damage, of tocilizumab versus placebo, both in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis. Patients will be randomized to receive tocilizumab 4 mg/kg IV, tocilizumab 8 mg/kg IV or placebo IV, every 4 weeks. All patients will also receive methotrexate, 10-25 mg/week. The anticipated time on study treatment is 1-2 years and the target sample size is 500+ individuals. After completion of the 2 year study participants could participate in the optional 3 year open label extension phase (year 3 to 5).

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: tocilizumab [RoActemra/Actemra] Drug: Placebo Drug: Methotrexate	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1196 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind Study of Safety and Prevention of Structural Joint Damage During Treatment With Tocilizumab Versus Placebo, in Combination With Methotrexate, in Patients With Moderate to Severe Rheumatoid Arthritis

Study Start Date :

Jan 1, 2005

Actual Primary Completion Date :

May 1, 2007

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.	Drug: tocilizumab [RoActemra/Actemra] 4 mg/kg or 8 mg/kg IV/month every 4 weeks. Other Names: RoActemra Actemra Drug: Methotrexate 10-25 mg/week
Experimental: Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.	Drug: tocilizumab [RoActemra/Actemra] 4 mg/kg or 8 mg/kg IV/month every 4 weeks. Other Names: RoActemra Actemra Drug: Methotrexate 10-25 mg/week
Placebo Comparator: Placebo + Methotrexate Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.	Drug: Placebo IV/month Drug: Methotrexate 10-25 mg/week

Arm

Intervention/Treatment

Experimental: Tocilizumab 4 mg/kg + Methotrexate

Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.

Drug: tocilizumab [RoActemra/Actemra]

4 mg/kg or 8 mg/kg IV/month every 4 weeks.

Other Names:

RoActemra

Actemra

Drug: Methotrexate

10-25 mg/week

Experimental: Tocilizumab 8 mg/kg + Methotrexate

Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.

Drug: tocilizumab [RoActemra/Actemra]

4 mg/kg or 8 mg/kg IV/month every 4 weeks.

Other Names:

RoActemra

Actemra

Drug: Methotrexate

10-25 mg/week

Placebo Comparator: Placebo + Methotrexate

Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.

Drug: Placebo

IV/month

Drug: Methotrexate

10-25 mg/week

Outcome Measures

Primary Outcome Measures

Percentage of Participants With American College of Rheumatology-ACR20 Response [Baseline, Week 24]
ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Change From Baseline in Modified Total Sharp-Genant Score at Week 52 [Baseline, Week 52]
Radiographs were taken of each hand and foot at Baseline and Week 52 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 (normalized from 98) and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 (normalized from 104) and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Change in Physical Function as Measured by the Area Under the Curve (AUC) for the Change From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 52 [Baseline to Week 52]
HAQ-DI consisted of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities rated on a 4-point scale where 0=without any difficulty to 3=unable to do. The sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst). Functional disability was determined as a cumulative measure of HAQ-DI over 1 year by using the AUC of the change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI indicate a greater average improvement in physical function over time and represent a decrease in sustained impairment. For patients with missing week 52 HAQ-DI score, the AUC of the change from baseline was standardized to 52 weeks using the latest timepoint available for calculation of the AUC. The mean was adjusted for region. A negative change from baseline indicated improvement.
Change From Baseline in the Modified Total Sharp-Genant Score at Week 104 [Baseline, Week 104]
Radiographs of each hand and foot were taken at Baseline and Week 104 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Change in Physical Function as Measured by the Area Under the Curve for the Change From Baseline in the Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 104 [Baseline to Week 104]
HAQ-DI consisted of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities rated on a 4-point scale where 0=without any difficulty to 3=unable to do. The sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst). Functional disability was determined as a cumulative measure of HAQ-DI over 2 years by using the AUC of the change from baseline in HAQ-DI score through week 104. Decreases in AUC of change from baseline in HAQ-DI indicated a gr eater average improvement in physical function over time and represent a decrease in sustained impairment. For patients with missing week 104 HAQ-DI score, the AUC of the change from baseline was standardized to 104 weeks using the latest timepoint available for calculation of the AUC. A negative change from baseline indicated improvement.

Secondary Outcome Measures

Percentage of Participants With ACR50 Response [Baseline, Week 24]
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
Percentage of Participants With ACR70 Response [Baseline,Week 24]
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
Swollen Joint Count (66 Joint Count): Mean Change From Baseline at Week 24 [Baseline, Week 24]
66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.
Tender Joint Count (68 Joint Count): Mean Change From Baseline at Week 24 [Baseline, Week 24]
68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68.
Patient's Global Visual Analog Scale (VAS): Mean Change From Baseline at Week 24 [Baseline, Week 24]
The patient's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Physician's Global VAS: Mean Change From Baseline at Week 24 [Baseline, Week 24]
The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).
Patient's Pain VAS: Mean Change From Baseline at Week 24 [Baseline and Week 24]
The patient assessed their pain on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change indicated improvement.
C-Reactive Protein (CRP): Mean Change From Baseline at Week 24 [Baseline, Week 24]
The serum concentration of C-Reactive Protein (CRP) is measured in mg/dL. A reduction in the level is considered an improvement.
Erythrocyte Sedimentation Rate: Mean Change From Baseline at Week 24 [Baseline, Week 24]
The Erythrocyte Sedimentation Rate (ESR) was measured in mm/hr. A reduction in the level is considered an improvement.
Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Week 24 [Baseline, Week 24]
HAQ-DI is a self-completed patient questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.
Percentage of Participants With American College of Rheumatology (ACR20) Response at Week 52 [Baseline, Week 52]
ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Percentage of Participants With ACR20 Response at Week 104 [Baseline, Week 104]
ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Percentage of Participants With ACR50 Response at Week 52 [Baseline, Week 52]
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Percentage of Participants With ACR50 Response at Week 104 [Baseline, Week 104]
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Percentage of Participants With ACR70 Response at Week 52 [Baseline, Week 52]
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Percentage of Participants With ACR70 Response at Week 104 [Baseline, Week 104]
ACR50 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Percentage of Participants With ACR70 Response Maintained for 6 Consecutive Months [104 Weeks]
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Change From Baseline in Swollen Joint Count at Week 52 [Baseline, Week 52]
66 joints were assessed at Baseline and Week 52 for swelling and joints are classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.
Change From Baseline in Tender Joint Count at Week 52 [Baseline, Week 52]
68 joints were assessed at Baseline and Week 52 for tenderness and joints were classified as tender/not tender for a total possible tender joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.
Change From Baseline in Patient's Global Assessment of Disease Activity at Week 52 [Baseline, Week 52]
The patient's global assessment of disease activity is assessed at Baseline and Week 52 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Change From Baseline in Physicians Global Assessment of Disease Activity at Week 52 [Baseline, Week 52]
The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Change From Baseline in the Patient's Pain VAS at Week 52 [Baseline, Week 52]
The patient assessed their pain at Baseline and Week 52 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.
Change From Baseline in C-Reactive Protein (CRP) at Week 52 [Baseline, Week 52]
Blood was collected for C-Reactive Protein (CRP) at Baseline and Week 52 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52 [Baseline, Week 52]
Blood was collected for Erythrocyte Sedimentation Rate (ESR) at Baseline and Week 52 and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.
Change From Baseline in Swollen Joint Count at Week 104 [Baseline, Week 104]
66 joints were assessed at Baseline and Week 104 for swelling and joints were classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.
Change From Baseline in Tender Joint Count at Week 104 [Baseline, Week 104]
68 joints were assessed for tenderness and joints were classified as tender/not tender for a total possible tender joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.
Change From Baseline in Patient's Global Assessment of Disease Activity at Week 104 [Baseline, Week 104]
The patient's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Change From Baseline in Physicians Global Assessment of Disease Activity at Week 104 [Baseline, Week 104]
The physician's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Change From Baseline in the Patient's Pain VAS at Week 104 [Baseline, Week 104]
The patient assessed their pain at Baseline and Week 104 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.
Change From Baseline in C-Reactive Protein (CRP) at Week 104 [Baseline, Week 104]
Blood was collected for C-Reactive Protein (CRP) at Baseline and Week 104 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 104 [Baseline, Week 104]
Blood was collected for Erythrocyte Sedimentation Rate (ESR) at Baseline and Week 104 and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.
Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 52 [Baseline, Week 52]
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do). HAQ-DI=sum of worst scores in each domain divided by the number of domains answered for a total possible score of 0 (best) to 3 (worst).
Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 104 [Baseline, Week 104]
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered for a total possible score of 0 (best) to 3 (worst). .
Area Under Curve (AUC) of the ACRn to Week 24 [24 Weeks]
The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 24. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.
Area Under Curve (AUC) of the ACRn to Week 52 [52 Weeks]
The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 52. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.
Area Under Curve (AUC) of the ACRn Score at Week 104 [104 Weeks]
The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 104. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.
Change From Baseline in Disease Activity Score (DAS28) at Week 24 [Baseline, Week 24]
The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
Change From Baseline in Disease Activity Score (DAS28) at Week 52 [Baseline, Week 52]
The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
Change From Baseline in Disease Activity Score (DAS28) at Week 104 [Baseline, Week 104]
The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 24 [Baseline, Week 24]
The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 52 [Baseline, Week 52]
The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm) [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 104 [Baseline, Week 104]
The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm) [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.
Percentage of Participants With DAS28 Remission at Week 24 [Week 24]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 remission is defined as a DAS28 score <2.6.
Percentage of Participants With DAS28 Remission at Week 52 [Week 52]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control.DAS28 Remission is defined as a DAS28 score <2.6.
Percentage of Participants With DAS28 Remission at Week 104 [Week 104]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score <2.6.
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 24 [24 Weeks]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 52 [52 Weeks]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 104 [104 Weeks]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).
Change From Baseline in Modified Total Sharp-Genant Score at Week 24 [Baseline, Week 24]
Radiographs were taken of each hand and foot at Baseline and Week 24 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Change From Baseline in Modified Total Sharp-Genant Score at Week 80 [Baseline, Week 80]
Radiographs were taken of each hand and foot at Baseline and Week 80 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Change From Baseline in Erosion Score at Week 24 [Baseline, Week 24]
Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Change From Baseline in Erosion Score at Week 52 [Baseline, Week 52]
Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Change From Baseline in Erosion Score at Week 80 [Baseline, Week 80]
Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Change From Baseline in Erosion Score at Week 104 [Baseline, Week 104]
Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Change From Baseline in Joint Space Narrowing Score at Week 24 [Baseline, Week 24]
Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower change from Baseline indicated a better score.
Change From Baseline in Joint Space Narrowing Score at Week 52 [Baseline, Week 52]
Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.
Change From Baseline in Joint Space Narrowing Score at Week 80 [Baseline, Week 80]
Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.
Change From Baseline in Joint Space Narrowing Score at Week 104 [Baseline, Week 104]
Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.
Percentage of Participants With no Progression of Erosion at Week 24 [Baseline, Week 24]
Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.
Percentage of Participants With no Progression of Erosion at Week 52 [Baseline, Week 52]
Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.
Percentage of Participants With no Progression of Erosion at Week 104 [Baseline, Week 104]
Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.
Percentage of Participants With no Progression of Joint Space Narrowing at Week 24 [Baseline, Week 24]
Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score was defined as a change from Baseline of less than or equal to zero.
Percentage of Participants With no Progression of Joint Space Narrowing at Week 52 [Baseline, Week 52]
Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score is defined as a change from Baseline of less than or equal to zero.
Percentage of Participants With no Progression of Joint Space Narrowing at Week 104 [Baseline, Week 104]
Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score is defined as a change from Baseline of less than or equal to zero.
Change From Baseline in HAQ Disability Index (HAQ-DI) at Week 52 [Baseline, Week 52]
HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.
Change From Baseline in HAQ Disability Index at Week 104 [Baseline, Week 104]
HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8). Total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.
Change From Baseline in Quality Life Short Form-36 (SF-36) Score at Week 24 [Baseline, Week 24]
The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.
Change From Baseline in SF-36 Score at Week 52 [Baseline, Week 52]
The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from Baseline indicates improvement.
Change From Baseline in SF-36 Score at Week 104 [Baseline, Week 104]
The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from Baseline indicated improvement.
Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score at Week 24 [Baseline, Week 24]
FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.
Change From Baseline in FACIT-F Score at Week 52 [Baseline, Week 52]
FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.
Change From Baseline in FACIT-F Score at Week 104 [Baseline, Week 104]
FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.
Change From Baseline in Rheumatoid Factor (RF) at Week 24 in Those Patients With Positive RF [Baseline, Week 24]
Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 24 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.
Change From Baseline in Rheumatoid Factor (RF) at Week 52 in Those Patients With Positive RF [Baseline, Week 52]
Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 52 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.
Change From Baseline in Rheumatoid Factor (RF) at Week 104 in Those Patients With Positive RF [Baseline, Week 104]
Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 104 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.
Time to Onset of ACR20 by Treatment Group [6 months]
Time in days until ACR20 response. ACR20 response was defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time to Onset of ACR50 by Treatment Group [6 months]
Time in days until ACR50 response. ACR50 response was defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time to Onset of ACR70 by Treatment Group [6 months]
Time in days until ACR70 response. ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Percentage of Participants Who Withdraw Due to Lack of Sufficient Therapeutic Response [104 Weeks]
Insufficient therapeutic response (patient not responding to the drug as assessed by the physician) was selected by the investigator as a reason that the patient withdrew from the study.
Percentage of Participants in Each Treatment Group Who Receive Escape Therapy [104 Weeks]
In Escape 1, participants in the Tocilizumab 4 mg/kg + Methotrexate and Tocilizumab 8 mg/kg + Methotrexate groups received tocilizumab 8 mg/kg as escape therapy. Participants in the Placebo + Methotrexate group received tocilizumab 4 mg/kg as escape therapy. In Escape 2, all participants received tocilizumab 8 mg/kg.
Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 24 [24 Weeks]
The percentage of participants, who achieved ACR remission at any study visit up to Week 24. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.
Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 52 [52 Weeks]
The percentage of participants, who achieved ACR remission at any study visit up to Week 52. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.
Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 104 [104 Weeks]
The percentage of participants who achieved ACR remission at any study visit up to Week 104. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.
Percentage of Participants Who Achieved Complete Clinical Response at Week 52 [52 Weeks]
Complete clinical response is defined as a continuous 6-month period of remission by ACR criteria [defined as five of the following criteria are met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or swelling, and ESR < 30 mm/hr for a female or 20 mm/hr for a male] and no radiographic progression [defined as change from baseline ≤ 0 in the total Sharp-Genant score, erosion score, and JSN score]. Patients who achieve a complete clinical response at any time in the study are counted as responders, even if the response is not maintained.
Percentage of Participants Who Achieved Complete Clinical Response at Week 104 [104 Weeks]
Complete clinical response is defined as a continuous 6-month period of remission by ACR criteria [defined as five of the following criteria are met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or swelling, and ESR < 30 mm/hr for a female or 20 mm/hr for a male] and no radiographic progression [defined as change from baseline ≤ 0 in the total Sharp-Genant score, erosion score, and JSN score].
End of Study: Percentage of Participants With ACR Response at Week 260 [Baseline, Week 260]
ACR20/50/70/90 response is defined as a ≥ 20/50/70/90% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
End of Study: Percentage of Participants With DAS28 Remission at Week 260 [Week 260]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score <2.6.
End of Study: Percentage of Participants With DAS28 Low Disease Activity (LDA) at Week 260 [Week 260]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDA is defined as DAS28 ≤3.2.
End of Study: Percentage of Participants With DAS28 European League Against Rheumatism (EULAR) Good or Moderate Response at Week 260 [Baseline, Week 260]
The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. EULAR Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.
End of Study: Change From Baseline in Swollen Joint Count at Week 260 [Baseline, Week 260]
66 joints were assessed at Baseline and Week 260 for swelling and joints are classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.
End of Study: Change From Baseline in Tender Joint Count at Week 260 [Baseline, Week 260]
68 joints were assessed at Baseline and Week 260 for tenderness and joints are classified as tender/not tender for a total possible swollen joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.
End of Study: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 260 [Baseline, Week 260]
HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.
End of Study: Change From Baseline in the Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) at Week 260 [Baseline, Week 260]
The patient's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
End of Study: Change From Baseline in the Physician's Global Assessment of Disease Activity VAS at Week 260 [Baseline, Week 260]
The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
End of Study: Change From Baseline in the Patient's Pain VAS at Week 260 [Baseline, Week 260]
The patient assessed their pain at Baseline and Week 260 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.
End of Study: Percentage of Participants With Clinical Improvement in the FACIT-Fatigue Score at Week 260 [Baseline, Week 260]
FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Clinically relevant improvement is defined as a ≥5 change from Baseline.
End of Study: Percentage of Participants With Clinical Relevant Improvement in the SF-36 Score at Week 260 [Baseline, Week 260]
The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. Clinically relevant improvement is defined as a ≥5 change from Baseline.
End of Study: Change From Baseline in Total Sharp-Genant Score at Week 260 [Baseline, Week 260]
Radiographs were taken of each hand and foot at Baseline and Week 260 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint).The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score. The results were reported based on the treatment the patient was originally randomized to.
End of Study: Change From Baseline in Erosion Score at Week 260 [Baseline, Week 260]
Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot and were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best ) to 142 (worst). A lower number change from Baseline indicated a better score.
End of Study: Change From Baseline in Joint Space Narrowing Score at Week 260 [Baseline, Week 260]
Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

adult patients at least 18 years of age with moderate to severe active RA for at least 6 months;
inadequate response to a stable dose of MTX;
patients of reproductive potential must be using reliable methods of contraception.

Exclusion Criteria:

major surgery (including joint surgery) within 8 weeks before entering study, or planned surgery within 6 months after entering study;
prior treatment failure with an anti-tumor necrosis factor agent;
women who are pregnant or breast-feeding.

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Birmingham	Alabama	United States	35233-7333
2	Huntsville	Alabama	United States	35801
3	Scottsdale	Arizona	United States	85251
4	Tucson	Arizona	United States	85724
5	Anaheim	California	United States	92801
6	Long Beach	California	United States	90806
7	Los Angeles	California	United States	90095
8	San Diego	California	United States	92108
9	San Francisco	California	United States	94118
10	Santa Maria	California	United States	93454
11	Torrance	California	United States	90505
12	Boulder	Colorado	United States	80304
13	Colorado Springs	Colorado	United States	80910
14	Denver	Colorado	United States	80230
15	Aventura	Florida	United States	33180
16	Fort Lauderdale	Florida	United States	33334
17	Tampa	Florida	United States	33614
18	West Palm Beach	Florida	United States	33407
19	Boise	Idaho	United States	83702
20	Coeur D'alene	Idaho	United States	83814
21	Idaho Falls	Idaho	United States	83404
22	Meridan	Idaho	United States	83642
23	Chicago	Illinois	United States	60612-3824
24	Rockford	Illinois	United States	61103
25	Indianapolis	Indiana	United States	46202-5100
26	Lexington	Kentucky	United States	40515
27	Frederick	Maryland	United States	21702
28	Hagerstown	Maryland	United States	21740
29	Wheaton	Maryland	United States	20902
30	Saint Louis	Missouri	United States	63131
31	St Louis	Missouri	United States	63141
32	Billings	Montana	United States	59101
33	Missoula	Montana	United States	59802
34	Reno	Nevada	United States	89502
35	Dover	New Hampshire	United States	03820
36	Medford	New Jersey	United States	08055
37	Voorhees	New Jersey	United States	08043
38	Albany	New York	United States	12206
39	Brooklyn	New York	United States	11201
40	Lake Success	New York	United States	11042
41	New York	New York	United States	10016
42	Stony Brook	New York	United States	11794-8161
43	Asheville	North Carolina	United States	28801
44	Charlotte	North Carolina	United States	28211
45	Raleigh	North Carolina	United States	27609
46	Wilmington	North Carolina	United States	28401
47	Canton	Ohio	United States	44718
48	Oklahoma City	Oklahoma	United States	73109
49	Tulsa	Oklahoma	United States	74135
50	Eugene	Oregon	United States	97401
51	Bethlehem	Pennsylvania	United States	18015
52	Duncansville	Pennsylvania	United States	16635
53	Philadelphia	Pennsylvania	United States	19140
54	Wyomissing	Pennsylvania	United States	19610
55	Columbia	South Carolina	United States	29204
56	Nashville	Tennessee	United States	37203
57	Dallas	Texas	United States	75231
58	San Antonio	Texas	United States	78217
59	Olympia	Washington	United States	98502
60	Seattle	Washington	United States	98104
61	Glendale	Wisconsin	United States	53217
62	Adelaide		Australia	5011
63	Malvern		Australia	3144
64	Melbourne		Australia	3168
65	New Lambton		Australia	2305
66	Shenton Park		Australia	6008
67	St. Leonards		Australia	2139
68	Porto Alegre		Brazil	91350-200
69	Rio de Janeiro		Brazil	20551-030
70	Sao Paulo		Brazil	01221-020
71	Sao Paulo		Brazil	04026-000
72	Sao Paulo		Brazil	5403900
73	Beijing		China	100032
74	Beijing		China	100044
75	Nanjing		China	210008
76	Shanghai		China	200127
77	Shanghai		China	200433
78	Hellerup		Denmark	2900
79	Odense		Denmark	5000
80	Heinola		Finland	18120
81	Helsinki		Finland	00290
82	Oulu		Finland	90029
83	Vantaa		Finland	01400
84	Amiens		France	80054
85	Bobigny		France	93009
86	Bois Guillaume		France	76233
87	Bordeaux		France	33076
88	Le Kremlin Bicetre		France	94270
89	Lille		France	59037
90	Nice		France	06202
91	Orleans		France	45000
92	Paris		France	75651
93	Paris		France	75877
94	Strasbourg		France	67098
95	Toulouse		France	31059
96	Vandoeuvre-les-nancy		France	54511
97	Athens		Greece	11527
98	Athens		Greece	15121
99	Athens		Greece	15127
100	Heraklion		Greece	71110
101	Brescia		Italy	25123
102	Coppito		Italy	67100
103	Firenze		Italy	50139
104	Genova		Italy	16132
105	Milano		Italy	20122
106	Milano		Italy	20157
107	Napoli		Italy	80131
108	Padova		Italy	35128
109	Pavia		Italy	27100
110	Pisa		Italy	56100
111	Reggio Emilia		Italy	42100
112	Roma		Italy	00161
113	Torino		Italy	10128
114	Udine		Italy	33100
115	Valeggio Sul Mincio		Italy	37067
116	Varese		Italy	21100
117	Verona		Italy	37134
118	Chihuahua		Mexico	31000
119	Mexico City		Mexico	03100
120	Mexico City		Mexico	06700
121	Mexico City		Mexico	06726
122	Mexico City		Mexico	07360
123	Monterrey		Mexico	64460
124	Obregon		Mexico	85000
125	Haugesund		Norway	5528
126	Lillehammer		Norway	2609
127	Tromsø		Norway	9038
128	Bydgoszcz		Poland	85-168
129	Dzialdowo		Poland	13-200
130	Elblag		Poland	82-300
131	Kalisz		Poland	62-800
132	Krakow		Poland	30-119
133	Krakow		Poland	30-510
134	Poznan		Poland	60-218
135	Szczecin		Poland	71-252
136	Ustron		Poland	43-450
137	Warszawa		Poland	00-909
138	Warszawa		Poland	02-637
139	Ponce		Puerto Rico	00716
140	San Juan		Puerto Rico	00936-5067
141	Cape Town		South Africa	4001
142	Cape Town		South Africa	7405
143	Cape Town		South Africa	7500
144	Diepkloof		South Africa	1862
145	Barcelona		Spain	08036
146	Cádiz		Spain	11009
147	Merida		Spain	97500
148	Sabadell		Spain	08208
149	Santander		Spain	39008
150	Sevilla		Spain	41009
151	Lausanne		Switzerland	1011
152	St. Gallen		Switzerland	9007

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT00106535

Other Study ID Numbers:

WA17823

First Posted:

Mar 28, 2005

Last Update Posted:

Feb 6, 2014

Last Verified:

Dec 1, 2013

Additional relevant MeSH terms:

Arthritis

Arthritis, Rheumatoid

Methotrexate

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	This study was divided into two phases: a 2-year core placebo controlled treatment phase and an optional 3-year extension phase.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate	All Tocilizumab Exposure + MTX
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.	Tocilizumab (TCZ) 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension (LTE) period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.	All tocilizumab (TCZ) exposure + methotrexate (MTX) group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either Placebo, Tocilizumab 4 mg/kg or Tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received 8 mg/kg IV every 4 weeks.
Period Title: 2-year Placebo Controlled Period
STARTED	394	401	401	0
Intent-to-treat: Received Study Drug	393	399	398	0
Safety: Actual Treatment Received	392	399	399	0
Completed Week 24	356	373	366	0
Completed Week 52	326	342	338	0
COMPLETED	287	309	310	0
NOT COMPLETED	107	92	91	0
Period Title: 2-year Placebo Controlled Period
STARTED	0	0	0	894
COMPLETED	0	0	0	704
NOT COMPLETED	0	0	0	190

Baseline Characteristics

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate	Total
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Total of all reporting groups
Overall Participants	393	399	398	1190
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.3 (12.41)	51.4 (12.59)	53.4 (11.72)	52.0 (12.24)
Sex: Female, Male (Count of Participants)
Female	328 83.5%	336 84.2%	325 81.7%	989 83.1%
Male	65 16.5%	63 15.8%	73 18.3%	201 16.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With American College of Rheumatology-ACR20 Response
Description	ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	27.0 6.9%	50.6 12.7%	56.3 14.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Percentage of Participants With ACR50 Response
Description	ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	9.7 2.5%	25.1 6.3%	32.2 8.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

3. Secondary Outcome

Title	Percentage of Participants With ACR70 Response
Description	ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
Time Frame	Baseline,Week 24

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	2.0 0.5%	11.0 2.8%	12.6 3.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

4. Secondary Outcome

Title	Swollen Joint Count (66 Joint Count): Mean Change From Baseline at Week 24
Description	66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for swollen joint counts. All assessments were set to missing from the time a patient received escape therapy and only pre-escape therapy joint count assessments were carried forward.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Baseline Swollen Joint Count (SJC)	16.6 (9.23)	17.0 (9.78)	17.3 (9.48)
Change from Baseline at Week 24 (n=391,399, 397)	-2.9 (10.37)	-7.9 (9.31)	-9.0 (9.76)

5. Secondary Outcome

Title	Tender Joint Count (68 Joint Count): Mean Change From Baseline at Week 24
Description	68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. LOCF was used for swollen joint counts. All assessments were set to missing from the time a patient received escape therapy and only pre-escape therapy joint count assessments were carried forward.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Baseline Tender Joint Count (TJC)	27.9 (14.80)	27.9 (14.15)	29.3 (15.22)
Change from Baseline at Week 24 (n=391,399, 397)	-4.8 (14.61)	-12.2 (14.94)	-14.2 (14.58)

6. Secondary Outcome

Title	Patient's Global Visual Analog Scale (VAS): Mean Change From Baseline at Week 24
Description	The patient's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. No imputation was used for missing VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Baseline Patient Visual Analog Scale (VAS)	63.1 (23.36)	61.0 (23.25)	62.7 (22.49)
Change from Baseline at Week 24 (n=213,308,316)	-17.5 (26.60)	-25.2 (27.09)	-25.2 (24.95)

7. Secondary Outcome

Title	Physician's Global VAS: Mean Change From Baseline at Week 24
Description	The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. No imputation was used for missing VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Baseline Physician's Visual Analog Scale (VAS)	63.1 (17.34)	62.3 (16.8)	62.7 (16.90)
Change from Baseline at Week 24 (n=214,307,320)	-29.0 (24.35)	-36.1 (24.31)	-39.8 (21.82)

8. Secondary Outcome

Title	Patient's Pain VAS: Mean Change From Baseline at Week 24
Description	The patient assessed their pain on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change indicated improvement.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. No imputation used for missing VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Baseline Patient Pain Visual Analog Scale (VAS)	55.3 (22.07)	53.3 (21.97)	55.7 (22.34)
Change from Baseline at Week 24 (n=213,308,317)	-12.5 (24.92)	-19.5 (25.24)	-21.8 (25.93)

9. Secondary Outcome

Title	C-Reactive Protein (CRP): Mean Change From Baseline at Week 24
Description	The serum concentration of C-Reactive Protein (CRP) is measured in mg/dL. A reduction in the level is considered an improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. No imputation was used for missing CRP. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Baseline C-Reactive Protein (CRP)	2.235 (2.5068)	2.076 (2.3892)	2.337 (2.6065)
Change from Baseline at Week 24 (n=214,308,321)	-0.3560 (2.12778)	-0.9558 (2.35222)	-2.0699 (2.50035)

10. Secondary Outcome

Title	Erythrocyte Sedimentation Rate: Mean Change From Baseline at Week 24
Description	The Erythrocyte Sedimentation Rate (ESR) was measured in mm/hr. A reduction in the level is considered an improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. No imputation was used for missing ESR. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Baseline Erythrocyte Sedimentation Rate (ESR)	46.5 (24.69)	45.9 (25.12)	46.4 (24.8)
Change from Baseline at Week 24 (n=211,304,318)	-9.5 (24.01)	-21.8 (23.71)	-36.8 (24.12)

11. Secondary Outcome

Title	Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Week 24
Description	HAQ-DI is a self-completed patient questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. No imputation was used for missing HAQ-DI. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Baseline HAQ-DI	1.5 (0.62)	1.5 (0.64)	1.5 (0.60)
Change from Baseline at Week 24 (n=197,292,301)	-0.32 (0.516)	-0.45 (0.531)	-0.51 (0.580)

12. Primary Outcome

Title	Change From Baseline in Modified Total Sharp-Genant Score at Week 52
Description	Radiographs were taken of each hand and foot at Baseline and Week 52 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 (normalized from 98) and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 (normalized from 104) and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat (ITT) population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Linear extrapolation was used to impute missing week 52 data. Data collected after withdrawal or on escape therapy is excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	290	339	348
Mean (Standard Deviation) [Score on a scale]	1.13 (2.962)	0.34 (1.451)	0.29 (1.282)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Van Elteren's test
	Comments	Stratified by region.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Van Elteren's test
	Comments	Stratified by region.

13. Primary Outcome

Title	Change in Physical Function as Measured by the Area Under the Curve (AUC) for the Change From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 52
Description	HAQ-DI consisted of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities rated on a 4-point scale where 0=without any difficulty to 3=unable to do. The sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst). Functional disability was determined as a cumulative measure of HAQ-DI over 1 year by using the AUC of the change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI indicate a greater average improvement in physical function over time and represent a decrease in sustained impairment. For patients with missing week 52 HAQ-DI score, the AUC of the change from baseline was standardized to 52 weeks using the latest timepoint available for calculation of the AUC. The mean was adjusted for region. A negative change from baseline indicated improvement.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing HAQ scores. All assessments were set to missing after a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	366	376	374
Least Squares Mean (Full Range) [Score on a scale*week]	-58.11 (150.839)	-128.37 (165.084)	-144.06 (173.372)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	Adjusted for region and original treatment group.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-70.26
	Confidence Interval	(2-Sided) 95% -96.96 to -43.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	Adjusted for region and original treatment group.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-85.95
	Confidence Interval	(2-Sided) 95% -112.69 to -59.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Primary Outcome

Title	Change From Baseline in the Modified Total Sharp-Genant Score at Week 104
Description	Radiographs of each hand and foot were taken at Baseline and Week 104 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Data collected after withdrawal or for patients on escape therapy the data is excluded. Missing data was imputed using linear extrapolation.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	294	343	353
Mean (Standard Deviation) [Score on a scale]	1.96 (5.956)	0.58 (2.357)	0.37 (1.547)

15. Primary Outcome

Title	Change in Physical Function as Measured by the Area Under the Curve for the Change From Baseline in the Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 104
Description	HAQ-DI consisted of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities rated on a 4-point scale where 0=without any difficulty to 3=unable to do. The sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst). Functional disability was determined as a cumulative measure of HAQ-DI over 2 years by using the AUC of the change from baseline in HAQ-DI score through week 104. Decreases in AUC of change from baseline in HAQ-DI indicated a gr eater average improvement in physical function over time and represent a decrease in sustained impairment. For patients with missing week 104 HAQ-DI score, the AUC of the change from baseline was standardized to 104 weeks using the latest timepoint available for calculation of the AUC. A negative change from baseline indicated improvement.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing HAQ scores. For patients who received escape therapy, the HAQ-DI was set to missing from the time they entered escape.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	366	376	374
Least Squares Mean (Full Range) [Score on a scale*week]	-139.40 (365.682)	-287.50 (383.201)	-320.80 (385.741)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	Adjusted for region.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-148.10
	Confidence Interval	(2-Sided) 95% -205.22 to -90.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	Adjusted for region.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-181.40
	Confidence Interval	(2-Sided) 95% -238.60 to -124.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology (ACR20) Response at Week 52
Description	ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	24.7 6.3%	47.9 12%	55.8 14%

17. Secondary Outcome

Title	Percentage of Participants With ACR20 Response at Week 104
Description	ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	29.3 7.5%	49.1 12.3%	54.5 13.7%

18. Secondary Outcome

Title	Percentage of Participants With ACR50 Response at Week 52
Description	ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	10.2 2.6%	30.3 7.6%	36.4 9.1%

19. Secondary Outcome

Title	Percentage of Participants With ACR50 Response at Week 104
Description	ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	19.8 5%	37.6 9.4%	38.9 9.8%

20. Secondary Outcome

Title	Percentage of Participants With ACR70 Response at Week 52
Description	ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	3.8 1%	16.5 4.1%	20.1 5.1%

21. Secondary Outcome

Title	Percentage of Participants With ACR70 Response at Week 104
Description	ACR50 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	12.2 3.1%	24.3 6.1%	22.4 5.6%

22. Secondary Outcome

Title	Percentage of Participants With ACR70 Response Maintained for 6 Consecutive Months
Description	ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	104 Weeks

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	5.6 1.4%	11.5 2.9%	14.3 3.6%

23. Secondary Outcome

Title	Change From Baseline in Swollen Joint Count at Week 52
Description	66 joints were assessed at Baseline and Week 52 for swelling and joints are classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for swollen joint counts. All assessments were set to missing from the time a patient received escape therapy and only pre-escape therapy joint count assessments were carried forward.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	391	399	397
Mean (Standard Deviation) [Joint count]	-2.5 (11.07)	-8.0 (9.95)	-10.2 (10.65)

24. Secondary Outcome

Title	Change From Baseline in Tender Joint Count at Week 52
Description	68 joints were assessed at Baseline and Week 52 for tenderness and joints were classified as tender/not tender for a total possible tender joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for missing tender joint data. All assessments were set to missing from the time a patient received escape therapy and only pre-escape therapy joint count assessments were carried forward.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	391	399	397
Mean (Standard Deviation) [Joint count]	-4.1 (15.53)	-12.3 (15.74)	-15.6 (16.04)

25. Secondary Outcome

Title	Change From Baseline in Patient's Global Assessment of Disease Activity at Week 52
Description	The patient's global assessment of disease activity is assessed at Baseline and Week 52 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	156	248	281
Mean (Standard Deviation) [Score on a scale]	-21.1 (26.22)	-27.2 (28.83)	-29.8 (25.61)

26. Secondary Outcome

Title	Change From Baseline in Physicians Global Assessment of Disease Activity at Week 52
Description	The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing VAS assessments. All assessments were set to missing after the patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	155	246	279
Mean (Standard Deviation) [Score on a scale]	-35.2 (25.13)	-42.2 (23.57)	-45.4 (22.22)

27. Secondary Outcome

Title	Change From Baseline in the Patient's Pain VAS at Week 52
Description	The patient assessed their pain at Baseline and Week 52 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing VAS assessments. Data was set to missing for patients who received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	156	248	282
Mean (Standard Deviation) [Score on a scale]	-15.0 (25.10)	-22.9 (25.70)	-26.1 (25.51)

28. Secondary Outcome

Title	Change From Baseline in C-Reactive Protein (CRP) at Week 52
Description	Blood was collected for C-Reactive Protein (CRP) at Baseline and Week 52 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was made for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	157	247	282
Mean (Standard Deviation) [mg/dL]	-0.3800 (2.50681)	-1.0615 (2.39897)	-2.2584 (2.71950)

29. Secondary Outcome

Title	Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52
Description	Blood was collected for Erythrocyte Sedimentation Rate (ESR) at Baseline and Week 52 and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing data. Data was set to missing for patients who received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	149	235	274
Mean (Standard Deviation) [mm/hr]	-10.9 (24.27)	-25.6 (24.68)	-38.5 (24.31)

30. Secondary Outcome

Title	Change From Baseline in Swollen Joint Count at Week 104
Description	66 joints were assessed at Baseline and Week 104 for swelling and joints were classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for swollen joint counts. All assessments were set to missing from the time a patient received escape therapy and only pre-escape therapy joint count assessments were carried forward.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	391	399	397
Mean (Standard Deviation) [Joint count]	-3.5 (11.65)	-9.0 (10.76)	-11.3 (11.31)

31. Secondary Outcome

Title	Change From Baseline in Tender Joint Count at Week 104
Description	68 joints were assessed for tenderness and joints were classified as tender/not tender for a total possible tender joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender joint counts. All assessments were set to missing from the time a patient received escape therapy and only pre-escape therapy joint count assessments were carried forward.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	391	399	397
Mean (Standard Deviation) [Joint count]	-5.9 (17.07)	-13.6 (16.53)	-17.7 (16.73)

32. Secondary Outcome

Title	Change From Baseline in Patient's Global Assessment of Disease Activity at Week 104
Description	The patient's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing VAS assessments. All assessments were set to missing from the time a patient received escape therapy

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	137	228	248
Mean (Standard Deviation) [Score on a scale]	-33.2 (26.35)	-31.6 (27.05)	-33.9 (26.60)

33. Secondary Outcome

Title	Change From Baseline in Physicians Global Assessment of Disease Activity at Week 104
Description	The physician's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	139	229	250
Mean (Standard Deviation) [Score on a scale]	-43.9 (21.55)	-49.1 (20.33)	-48.7 (22.20)

34. Secondary Outcome

Title	Change From Baseline in the Patient's Pain VAS at Week 104
Description	The patient assessed their pain at Baseline and Week 104 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	137	228	248
Mean (Standard Deviation) [Score on a scale]	-25.6 (24.44)	-26.6 (25.39)	-28.9 (25.47)

35. Secondary Outcome

Title	Change From Baseline in C-Reactive Protein (CRP) at Week 104
Description	Blood was collected for C-Reactive Protein (CRP) at Baseline and Week 104 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	139	231	251
Mean (Standard Deviation) [mg/dL]	-1.6346 (2.28001)	-1.6863 (2.20965)	-2.3068 (2.65256)

36. Secondary Outcome

Title	Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 104
Description	Blood was collected for Erythrocyte Sedimentation Rate (ESR) at Baseline and Week 104 and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	139	231	247
Mean (Standard Deviation) [mm/hr]	-30.7 (22.26)	-35.4 (25.07)	-36.9 (23.39)

37. Secondary Outcome

Title	Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 52
Description	The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do). HAQ-DI=sum of worst scores in each domain divided by the number of domains answered for a total possible score of 0 (best) to 3 (worst).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing for patients who received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	146	235	263
Number [Percentage of participants]	52.7 13.4%	59.6 14.9%	62.7 15.8%

38. Secondary Outcome

Title	Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 104
Description	The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered for a total possible score of 0 (best) to 3 (worst). .
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	127	218	231
Number [Percentage of participants]	58.3 14.8%	63.3 15.9%	62.3 15.7%

39. Secondary Outcome

Title	Area Under Curve (AUC) of the ACRn to Week 24
Description	The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 24. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ score, CRP, ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	216	308	320
Mean (Standard Deviation) [Score on a scale*week]	609.11 (5551.669)	2791.49 (5479.514)	3528.89 (5812.582)

40. Secondary Outcome

Title	Area Under Curve (AUC) of the ACRn to Week 52
Description	The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 52. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.
Time Frame	52 Weeks

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population(all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ score, CRP, ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	156	247	279
Least Squares Mean (Full Range) [Score on a scale*week]	5551.25 (6080.038)	10763.54 (7488.703)	12644.01 (7248.249)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	Adjusted for region.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5212.28
	Confidence Interval	(2-Sided) 95% 3139.40 to 7285.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Adjusted for region.
	Method	ANOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7092.76
	Confidence Interval	(2-Sided) 95% 5066.16 to 9119.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

41. Secondary Outcome

Title	Area Under Curve (AUC) of the ACRn Score at Week 104
Description	The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 104. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.
Time Frame	104 Weeks

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ score, CRP, ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	138	228	249
Mean (Standard Deviation) [Score on a scale*week]	21094.97 (22341.489)	27141.08 (24296.659)	30876.59 (18177.420)

42. Secondary Outcome

Title	Change From Baseline in Disease Activity Score (DAS28) at Week 24
Description	The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	208	301	311
Mean (Standard Deviation) [Score on a scale]	-1.49 (1.257)	-2.45 (1.401)	-3.28 (1.383)

43. Secondary Outcome

Title	Change From Baseline in Disease Activity Score (DAS28) at Week 52
Description	The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	153	247	273
Mean (Standard Deviation) [Score on a scale]	-1.88 (1.319)	-2.97 (1.391)	-3.80 (1.263)

44. Secondary Outcome

Title	Change From Baseline in Disease Activity Score (DAS28) at Week 104
Description	The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	134	223	238
Mean (Standard Deviation) [Score on a scale]	-3.70 (1.416)	-3.82 (1.306)	-4.14 (1.344)

45. Secondary Outcome

Title	Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 24
Description	The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
ITT population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. For patients who received escape therapy, withdrew prematurely or where the DAS28 score was missing the response was set to 'No response'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Good EULAR Response	5.9 1.5%	24.6 6.2%	40.7 10.2%
Moderate EULAR Response	28.8 7.3%	39.6 9.9%	33.7 8.5%

46. Secondary Outcome

Title	Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 52
Description	The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm) [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
ITT population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. For patients who received escape therapy, withdrew prematurely or where the DAS28 score was missing the response was set to 'No response'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Good Response	7.1 1.8%	27.6 6.9%	44.0 11.1%
Moderate Response	22.1 5.6%	30.3 7.6%	24.1 6.1%

47. Secondary Outcome

Title	Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 104
Description	The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm) [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
ITT population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation was used for missing ESR and VAS assessments. For patients who received escape therapy, withdrew prematurely or where the DAS28 score was missing the response was set to 'No response'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Good Response	23.4 6%	39.6 9.9%	45.7 11.5%
Moderate Response	9.7 2.5%	15.8 4%	13.1 3.3%

48. Secondary Outcome

Title	Percentage of Participants With DAS28 Remission at Week 24
Description	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 remission is defined as a DAS28 score <2.6.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	212	304	315
Number [Percentage of participants]	3.8 1%	17.8 4.5%	33.3 8.4%

49. Secondary Outcome

Title	Percentage of Participants With DAS28 Remission at Week 52
Description	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control.DAS28 Remission is defined as a DAS28 score <2.6.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	156	249	275
Number [Percentage of participants]	7.7 2%	30.5 7.6%	48.0 12.1%

50. Secondary Outcome

Title	Percentage of Participants With DAS28 Remission at Week 104
Description	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score <2.6.
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	136	224	241
Number [Percentage of participants]	52.9 13.5%	55.4 13.9%	64.7 16.3%

51. Secondary Outcome

Title	Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 24
Description	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	208	301	311
Mean (Standard Deviation) [Score on a scale*week]	895.85 (179.465)	767.02 (208.462)	670.45 (193.506)

52. Secondary Outcome

Title	Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 52
Description	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).
Time Frame	52 Weeks

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	146	230	265
Mean (Standard Deviation) [Score on a scale*week]	1755.25 (353.653)	1423.12 (415.188)	1235.80 (412.134)

53. Secondary Outcome

Title	Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 104
Description	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).
Time Frame	104 Weeks

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	134	223	238
Mean (Standard Deviation) [Score on a scale*week]	2793.01 (675.840)	2426.11 (743.882)	2094.71 (749.148)

54. Secondary Outcome

Title	Change From Baseline in Modified Total Sharp-Genant Score at Week 24
Description	Radiographs were taken of each hand and foot at Baseline and Week 24 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with Baseline and post-Baseline radiographic data available for this outcome measure. Data collected after withdraw or on escape therapy is excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	283	327	334
Mean (Standard Deviation) [Score on a scale]	0.51 (1.336)	0.22 (0.843)	0.19 (0.985)

55. Secondary Outcome

Title	Change From Baseline in Modified Total Sharp-Genant Score at Week 80
Description	Radiographs were taken of each hand and foot at Baseline and Week 80 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 80

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Linear extrapolation was used to impute missing data. Data collected after withdraw or on escape therapy is excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	294	343	353
Mean (Standard Deviation) [Score on a scale]	1.60 (4.658)	0.46 (1.845)	0.31 (1.273)

56. Secondary Outcome

Title	Change From Baseline in Erosion Score at Week 24
Description	Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Data was set to missing for patients who withdrew or received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	283	327	334
Mean (Standard Deviation) [Score on a scale]	0.36 (0.928)	0.15 (0.563)	0.11 (0.625)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0023
	Comments
	Method	Van Elteren's test
	Comments	Stratified by region.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Van Elteren's test
	Comments

57. Secondary Outcome

Title	Change From Baseline in Erosion Score at Week 52
Description	Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data for this outcome measure. Missing Week 52 data was imputed using Linear extrapolation. Data was set to missing for patients who withdrew or received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	290	339	348
Mean (Standard Deviation) [Score on a scale]	0.71 (1.892)	0.21 (0.920)	0.17 (0.860)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Van Elteren's test
	Comments	Stratified by region.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Van Elteren's test
	Comments	Stratified by region.

58. Secondary Outcome

Title	Change From Baseline in Erosion Score at Week 80
Description	Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 80

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Linear extrapolation was used to impute missing data. Data collected after withdraw or on escape therapy is excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	294	343	353
Mean (Standard Deviation) [Score on a scale]	1.01 (3.101)	0.27 (1.101)	0.18 (1.060)

59. Secondary Outcome

Title	Change From Baseline in Erosion Score at Week 104
Description	Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Linear extrapolation was used to impute missing data. Data collected after withdraw or on escape therapy is excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	294	343	353
Mean (Standard Deviation) [Score on a scale]	1.24 (3.947)	0.34 (1.337)	0.22 (1.301)

60. Secondary Outcome

Title	Change From Baseline in Joint Space Narrowing Score at Week 24
Description	Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower change from Baseline indicated a better score.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Data was set to missing for patients who withdrew or received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	283	327	334
Mean (Standard Deviation) [Score on a scale]	0.15 (0.659)	0.07 (0.416)	0.08 (0.468)

61. Secondary Outcome

Title	Change From Baseline in Joint Space Narrowing Score at Week 52
Description	Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdraw or on escape therapy was excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	290	339	348
Mean (Standard Deviation) [Score on a scale]	0.42 (1.695)	0.13 (0.739)	0.12 (0.640)

62. Secondary Outcome

Title	Change From Baseline in Joint Space Narrowing Score at Week 80
Description	Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 80

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdraw or on escape therapy was excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	294	343	353
Mean (Standard Deviation) [Score on a scale]	0.59 (2.589)	0.19 (1.035)	0.13 (0.626)

63. Secondary Outcome

Title	Change From Baseline in Joint Space Narrowing Score at Week 104
Description	Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdraw or on escape therapy was excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	294	343	353
Mean (Standard Deviation) [Score on a scale]	0.72 (3.321)	0.24 (1.368)	0.15 (0.772)

64. Secondary Outcome

Title	Percentage of Participants With no Progression of Erosion at Week 24
Description	Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Data collected after withdraw or on escape therapy was excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	283	327	334
Number [Percentage of participants]	73.9 18.8%	83.8 21%	88.3 22.2%

65. Secondary Outcome

Title	Percentage of Participants With no Progression of Erosion at Week 52
Description	Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdraw or on escape therapy was excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	290	339	348
Number [Percentage of participants]	70.0 17.8%	82.6 20.7%	86.8 21.8%

66. Secondary Outcome

Title	Percentage of Participants With no Progression of Erosion at Week 104
Description	Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdrawal or on escape therapy was excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	294	343	353
Number [Percentage of participants]	71.1 18.1%	78.4 19.6%	85.6 21.5%

67. Secondary Outcome

Title	Percentage of Participants With no Progression of Joint Space Narrowing at Week 24
Description	Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score was defined as a change from Baseline of less than or equal to zero.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Data collected after withdrawal or on escape therapy was excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	283	327	334
Number [Percentage of participants]	88.3 22.5%	91.4 22.9%	91.9 23.1%

68. Secondary Outcome

Title	Percentage of Participants With no Progression of Joint Space Narrowing at Week 52
Description	Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score is defined as a change from Baseline of less than or equal to zero.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdrawal or on escape therapy was excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	290	339	348
Number [Percentage of participants]	84.5 21.5%	90.6 22.7%	90.5 22.7%

69. Secondary Outcome

Title	Percentage of Participants With no Progression of Joint Space Narrowing at Week 104
Description	Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score is defined as a change from Baseline of less than or equal to zero.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdrawal or on escape therapy was excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	294	343	353
Number [Percentage of participants]	80.3 20.4%	86.0 21.6%	91.2 22.9%

70. Secondary Outcome

Title	Change From Baseline in HAQ Disability Index (HAQ-DI) at Week 52
Description	HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	146	235	263
Mean (Standard Deviation) [Score on a scale]	-0.39 (0.570)	-0.52 (0.607)	-0.58 (0.583)

71. Secondary Outcome

Title	Change From Baseline in HAQ Disability Index at Week 104
Description	HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8). Total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	127	218	231
Mean (Standard Deviation) [Score on a scale]	-0.50 (0.612)	-0.58 (0.608)	-0.61 (0.661)

72. Secondary Outcome

Title	Change From Baseline in Quality Life Short Form-36 (SF-36) Score at Week 24
Description	The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. . Data was set to missing for patients who received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	203	283	294
Physical component score	5.54 (8.459)	8.15 (8.135)	8.46 (8.520)
Mental component score	3.27 (11.092)	4.63 (11.702)	5.17 (10.869)

73. Secondary Outcome

Title	Change From Baseline in SF-36 Score at Week 52
Description	The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from Baseline indicates improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. Data was set to missing for patients who received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	144	230	261
Physical component summary score	5.6 (8.42)	9.2 (8.29)	10.0 (9.13)
Mental component summary score	3.7 (10.67)	5.6 (11.94)	5.5 (11.49)

74. Secondary Outcome

Title	Change From Baseline in SF-36 Score at Week 104
Description	The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from Baseline indicated improvement.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	130	211	228
Physical component score	8.7 (9.53)	10.1 (9.50)	9.8 (9.66)
Mental component score	5.2 (10.27)	5.7 (11.22)	6.2 (11.55)

75. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score at Week 24
Description	FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing FACIT-Fatigue scores. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	214	307	313
Mean (Standard Deviation) [Score on a scale]	5.32 (10.133)	7.14 (10.145)	6.91 (8.877)

76. Secondary Outcome

Title	Change From Baseline in FACIT-F Score at Week 52
Description	FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	157	250	276
Mean (Standard Deviation) [Score on a scale]	5.57 (10.087)	8.14 (10.880)	8.27 (9.387)

77. Secondary Outcome

Title	Change From Baseline in FACIT-F Score at Week 104
Description	FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	138	224	244
Mean (Standard Deviation) [Score on a scale]	6.62 (9.544)	7.85 (10.578)	8.63 (9.737)

78. Secondary Outcome

Title	Change From Baseline in Rheumatoid Factor (RF) at Week 24 in Those Patients With Positive RF
Description	Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 24 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with positive RF at Baseline. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	179	252	268
Mean (Standard Deviation) [IU/mL]	-44.7 (273.71)	-79.3 (315.06)	-75.6 (205.76)

79. Secondary Outcome

Title	Change From Baseline in Rheumatoid Factor (RF) at Week 52 in Those Patients With Positive RF
Description	Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 52 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with positive RF at Baseline. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	132	208	232
Mean (Standard Deviation) [IU/mL]	-21.5 (444.37)	8.6 (575.02)	-71.6 (213.45)

80. Secondary Outcome

Title	Change From Baseline in Rheumatoid Factor (RF) at Week 104 in Those Patients With Positive RF
Description	Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 104 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with positive RF at Baseline. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	115	191	206
Mean (Standard Deviation) [IU/mL]	-29.0 (304.46)	-25.1 (431.29)	-39.2 (253.29)

81. Secondary Outcome

Title	Time to Onset of ACR20 by Treatment Group
Description	Time in days until ACR20 response. ACR20 response was defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description
Participants from the ITT population [N=393,399,398] (all randomized participants who received study drug) with ACR20 response. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who withdrew, received escape therapy or who did not achieve a response were censored.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	209	299	328
Median (95% Confidence Interval) [Days]	116.0	57.0	57.0

82. Secondary Outcome

Title	Time to Onset of ACR50 by Treatment Group
Description	Time in days until ACR50 response. ACR50 response was defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description
Participants from the ITT population [N=393,399,398] (all randomized participants who received study drug) with ACR50 response. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who withdrew, received escape therapy or who did not achieve a response were censored.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	76	178	205
Median (95% Confidence Interval) [Days]	NA	170.0	141.0

83. Secondary Outcome

Title	Time to Onset of ACR70 by Treatment Group
Description	Time in days until ACR70 response. ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description
Participants from the ITT population [N=393,399,398] (all randomized participants who received study drug) with ACR70 response. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who withdrew, received escape therapy or who did not achieve a response were censored.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	23	89	95
Median (95% Confidence Interval) [Days]	NA	NA	NA

84. Secondary Outcome

Title	Percentage of Participants Who Withdraw Due to Lack of Sufficient Therapeutic Response
Description	Insufficient therapeutic response (patient not responding to the drug as assessed by the physician) was selected by the investigator as a reason that the patient withdrew from the study.
Time Frame	104 Weeks

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received at least 1 dose of study drug. Data on escape therapy is excluded.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	3.1 0.8%	0.3 0.1%	0.5 0.1%

85. Secondary Outcome

Title	Percentage of Participants in Each Treatment Group Who Receive Escape Therapy
Description	In Escape 1, participants in the Tocilizumab 4 mg/kg + Methotrexate and Tocilizumab 8 mg/kg + Methotrexate groups received tocilizumab 8 mg/kg as escape therapy. Participants in the Placebo + Methotrexate group received tocilizumab 4 mg/kg as escape therapy. In Escape 2, all participants received tocilizumab 8 mg/kg.
Time Frame	104 Weeks

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	392	399	398
Escape 1 Therapy	50 12.7%	24 6%	15 3.8%
Escape 2 Therapy	8 2%	2 0.5%	3 0.8%

86. Secondary Outcome

Title	Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 24
Description	The percentage of participants, who achieved ACR remission at any study visit up to Week 24. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for morning stiffness, FACIT-Fatigue score, ESR and VAS assessment. Patients with missing data, early withdrawal or who received escape therapy were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	0.0 0%	0.3 0.1%	0.0 0%

87. Secondary Outcome

Title	Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 52
Description	The percentage of participants, who achieved ACR remission at any study visit up to Week 52. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.
Time Frame	52 Weeks

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for morning stiffness, FACIT-Fatigue score, ESR and VAS assessment. Patients with missing data, early withdrawal or who received escape therapy were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	0.0 0%	1.8 0.5%	1.5 0.4%

88. Secondary Outcome

Title	Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 104
Description	The percentage of participants who achieved ACR remission at any study visit up to Week 104. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.
Time Frame	104 Weeks

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for morning stiffness, FACIT-Fatigue score, ESR and VAS assessment. Patients with missing data, early withdrawal or who received escape therapy were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	0.0 0%	2.0 0.5%	2.5 0.6%

89. Secondary Outcome

Title	Percentage of Participants Who Achieved Complete Clinical Response at Week 52
Description	Complete clinical response is defined as a continuous 6-month period of remission by ACR criteria [defined as five of the following criteria are met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or swelling, and ESR < 30 mm/hr for a female or 20 mm/hr for a male] and no radiographic progression [defined as change from baseline ≤ 0 in the total Sharp-Genant score, erosion score, and JSN score]. Patients who achieve a complete clinical response at any time in the study are counted as responders, even if the response is not maintained.
Time Frame	52 Weeks

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received at least 1 dose of study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	0.0 0%	0.3 0.1%	0.5 0.1%

90. Secondary Outcome

Title	Percentage of Participants Who Achieved Complete Clinical Response at Week 104
Description	Complete clinical response is defined as a continuous 6-month period of remission by ACR criteria [defined as five of the following criteria are met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or swelling, and ESR < 30 mm/hr for a female or 20 mm/hr for a male] and no radiographic progression [defined as change from baseline ≤ 0 in the total Sharp-Genant score, erosion score, and JSN score].
Time Frame	104 Weeks

Outcome Measure Data

Analysis Population Description
Intent-to-treat population included all randomized participants who received at least 1 dose of study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew or where an ACR could not be calculated, were set to 'Non Responder'.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab 4 mg/kg + Methotrexate	Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Measure Participants	393	399	398
Number [Percentage of participants]	0 0%	0.3 0.1%	1.0 0.3%

91. Secondary Outcome

Title	End of Study: Percentage of Participants With ACR Response at Week 260
Description	ACR20/50/70/90 response is defined as a ≥ 20/50/70/90% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treatment population, all exposure group, with data available at Baseline and Week 260. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	473
ACR 20 Response	82.9 21.1%
ACR 50 Response	64.9 16.5%
ACR 70 Response	42.1 10.7%
ACR 90 Response	16.7 4.2%

92. Secondary Outcome

Title	End of Study: Percentage of Participants With DAS28 Remission at Week 260
Description	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score <2.6.
Time Frame	Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treatment population, all exposure group, with data available at Week 260. Last observation carried forward was used for tender and swollen joint counts. No imputation used for ESR and Patients Global Assessment of Disease Activity VAS.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	458
Number [Percentage of participants]	59.4 15.1%

93. Secondary Outcome

Title	End of Study: Percentage of Participants With DAS28 Low Disease Activity (LDA) at Week 260
Description	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDA is defined as DAS28 ≤3.2.
Time Frame	Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treatment population, all exposure group, with data available at Week 260. Last observation carried forward was used for tender and swollen joint counts. No imputation used for ESR and Patients Global Assessment of Disease Activity VAS.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	458
Number [Percentage of participants]	73.8 18.8%

94. Secondary Outcome

Title	End of Study: Percentage of Participants With DAS28 European League Against Rheumatism (EULAR) Good or Moderate Response at Week 260
Description	The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. EULAR Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treatment population, all exposure group, with data available at Week 260. Last observation carried forward was used for tender and swollen joint counts. No imputation used for ESR and Patients Global Assessment of Disease Activity VAS.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	455
Good Response	74.1 18.9%
Moderate Response	24.0 6.1%

95. Secondary Outcome

Title	End of Study: Change From Baseline in Swollen Joint Count at Week 260
Description	66 joints were assessed at Baseline and Week 260 for swelling and joints are classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treat population, All Tocilizumab Exposure group, with data available at Baseline and Week 260. Last observation carried forward was used for missing joint counts.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	480
Mean (Standard Deviation) [Joint Count]	-14.2 (10.34)

96. Secondary Outcome

Title	End of Study: Change From Baseline in Tender Joint Count at Week 260
Description	68 joints were assessed at Baseline and Week 260 for tenderness and joints are classified as tender/not tender for a total possible swollen joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treat population, All Tocilizumab Exposure group, with data available at Baseline and Week 260. Last observation carried forward was used for missing joint counts.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	480
Mean (Standard Deviation) [Joint Count]	-23.6 (14.20)

97. Secondary Outcome

Title	End of Study: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 260
Description	HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treat population, All Tocilizumab Exposure group, with data available at Baseline and Week 260. No imputation was used for missing HAQ score.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	444
Mean (Standard Deviation) [Score on a scale]	-0.58 (0.657)

98. Secondary Outcome

Title	End of Study: Change From Baseline in the Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) at Week 260
Description	The patient's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treat population, all tocilizumab exposure group, with data available at Baseline and Week 260. No imputation was used for missing VAS assessments.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	471
Mean (Standard Deviation) [mm]	-33.7 (27.22)

99. Secondary Outcome

Title	End of Study: Change From Baseline in the Physician's Global Assessment of Disease Activity VAS at Week 260
Description	The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treat population, all tocilizumab exposure group, with data available at Baseline and Week 260. No imputation was used for missing VAS assessments.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	469
Mean (Standard Deviation) [mm]	-48.7 (21.70)

100. Secondary Outcome

Title	End of Study: Change From Baseline in the Patient's Pain VAS at Week 260
Description	The patient assessed their pain at Baseline and Week 260 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treat population, all tocilizumab exposure group, with data available at Baseline and Week 260. No imputation was used for missing VAS assessments.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	471
Mean (Standard Deviation) [mm]	-28.2 (26.78)

101. Secondary Outcome

Title	End of Study: Percentage of Participants With Clinical Improvement in the FACIT-Fatigue Score at Week 260
Description	FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Clinically relevant improvement is defined as a ≥5 change from Baseline.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treat population, All Tocilizumab Exposure group, with data available for analysis at Baseline and Week 260.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	473
Number [Percentage of participants]	64.1 16.3%

102. Secondary Outcome

Title	End of Study: Percentage of Participants With Clinical Relevant Improvement in the SF-36 Score at Week 260
Description	The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. Clinically relevant improvement is defined as a ≥5 change from Baseline.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Modified Intent-to-treat population, All Tocilizumab Exposure group, with data available for analysis at Baseline and Week 260.

Arm/Group Title	All Tocilizumab Exposure + MTX
Arm/Group Description	All tocilizumab exposure group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	442
Mental Components Summary	43.7 11.1%
Physical Components summary	69.9 17.8%

103. Secondary Outcome

Title	End of Study: Change From Baseline in Total Sharp-Genant Score at Week 260
Description	Radiographs were taken of each hand and foot at Baseline and Week 260 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint).The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score. The results were reported based on the treatment the patient was originally randomized to.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline, Week 104 and post-Week 104 radiographic data available for this outcome measure. Linear extrapolation was used to impute missing data.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.	All participants received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	258	545
Mean (Standard Deviation) [Score on a scale]	3.30 (6.093)	1.54 (4.272)

104. Secondary Outcome

Title	End of Study: Change From Baseline in Erosion Score at Week 260
Description	Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot and were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best ) to 142 (worst). A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline, Week 104 and post-Week 104 radiographic data available for this outcome measure. Linear extrapolation was used to impute missing data.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.	All participants received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	258	545
Mean (Standard Deviation) [Score on a scale]	1.95 (3.640)	0.83 (2.657)

105. Secondary Outcome

Title	End of Study: Change From Baseline in Joint Space Narrowing Score at Week 260
Description	Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.
Time Frame	Baseline, Week 260

Outcome Measure Data

Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline, Week 104 and post-Week 104 radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation.

Arm/Group Title	Placebo + Methotrexate	Tocilizumab + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.	All participants received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either: placebo, tocilizumab 4 mg/kg or tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received tocilizumab 8 mg/kg IV every 4 weeks.
Measure Participants	258	545
Mean (Standard Deviation) [Score on a scale]	1.35 (3.134)	0.71 (2.222)

Adverse Events

	Placebo + Methotrexate		All Tocilizumab 4 mg/kg + Methotrexate		All Tocilizumab 8 mg/kg + Methotrexate
Time Frame	Day 1 thru the End of the Study (Up to 6.0 years).
Adverse Event Reporting Description	Safety population included all participants who received study treatment based on the treatment actually received. The number of participants at risk is the number of participants in each arm with an adverse event recorded while receiving that treatment. Participants may be counted in more than one arm.

Arm/Group Title	Placebo + Methotrexate		All Tocilizumab 4 mg/kg + Methotrexate		All Tocilizumab 8 mg/kg + Methotrexate
Arm/Group Description	Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly. Total Exposure Placebo + MTX = 282.36 patient-years (PY).		All participants who received tocilizumab (TCZ) 4 mg/kg IV every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly during the study. Total exposure TCZ 4mg + MTX = 580.99 PY.		All participants who received tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly during the study. Total exposure TCZ 8mg + MTX = 3797.94 PY.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo + Methotrexate		All Tocilizumab 4 mg/kg + Methotrexate		All Tocilizumab 8 mg/kg + Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/392 (6.6%)		58/599 (9.7%)		267/1054 (25.3%)
Blood and lymphatic system disorders
Anemia	1/392 (0.3%)		0/599 (0%)		3/1054 (0.3%)
Neutropenia	0/392 (0%)		1/599 (0.2%)		1/1054 (0.1%)
Pancytopenia	0/392 (0%)		1/599 (0.2%)		1/1054 (0.1%)
Bicytopenia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Bone marrow failure	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Hilar lymphadenopathy	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Iron deficiency anaemia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Leukopenia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Microcytic anaemia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Thrombocytopenia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Cardiac disorders
Acute myocardial infarction	0/392 (0%)		2/599 (0.3%)		1/1054 (0.1%)
Atrial fibrillation	0/392 (0%)		0/599 (0%)		3/1054 (0.3%)
Coronary artery disease	0/392 (0%)		1/599 (0.2%)		5/1054 (0.5%)
Ventricular fibrillation	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Cardiac failure	0/392 (0%)		0/599 (0%)		3/1054 (0.3%)
Myocardial infarction	0/392 (0%)		0/599 (0%)		3/1054 (0.3%)
Angina pectoris	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Cardiac failure congestive	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Cardio-respiratory arrest	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Cardiomyopathy	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Coronary artery stenosis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Mitral valve incompetence	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Palpitations	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pericarditis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Sinus tachycardia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Supraventricular tachycardia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Ventricular hypokinesia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Endocrine disorders
Hyperthyroidism	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Goitre	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Hypothyroidism	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Eye disorders
Corneal perforation	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Retinal detachment	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Ulcerative keratitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Gastrointestinal disorders
Dysphagia	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Hiatus hernia	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Large intestinal ulcer	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Sigmoiditis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Abdominal pain	0/392 (0%)		0/599 (0%)		4/1054 (0.4%)
Diverticular perforation	0/392 (0%)		1/599 (0.2%)		1/1054 (0.1%)
Gastritis	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Ileus paralytic	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Pancreatitis	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Abdominal adhesions	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Abdominal pain lower	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Diverticulum intestinal	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Enteritis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Gastric ulcer	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Gastrointestinal telangiectasia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Haemorrhoidal haemorrhage	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Haemorrhoids	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Inflammatory bowel disease	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Inguinal hernia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Intestinal polyp	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Irritable bowel syndrome	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Mouth ulceration	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Pancreatic pseudocyst	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pancreatitis necrotising	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Rectal haemorrhage	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Umbilical hernia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
General disorders
Influenza like illness	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Device dislocation	0/392 (0%)		0/599 (0%)		4/1054 (0.4%)
Non-cardiac chest pain	0/392 (0%)		0/599 (0%)		4/1054 (0.4%)
Chest pain	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Death	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Infusion site reaction	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Hepatobiliary disorders
Cholelithiasis	1/392 (0.3%)		0/599 (0%)		4/1054 (0.4%)
Bile duct stone	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Cholecystitis acute	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Acute hepatic failure	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Autoimmune hepatitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Biliary tract disorder	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Cholecystitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Hepatic cirrhosis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Hepatic vein thrombosis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Hepatitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Portal vein thrombosis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Immune system disorders
Anaphylactic reaction	0/392 (0%)		2/599 (0.3%)		1/1054 (0.1%)
Anaphylactic shock	0/392 (0%)		2/599 (0.3%)		0/1054 (0%)
Drug hypersensitivity	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Infections and infestations
Pneumonia	2/392 (0.5%)		3/599 (0.5%)		16/1054 (1.5%)
Gastroenteritis	2/392 (0.5%)		2/599 (0.3%)		3/1054 (0.3%)
Osteomyelitis	0/392 (0%)		1/599 (0.2%)		1/1054 (0.1%)
Otitis media	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Respiratory tract infection	0/392 (0%)		1/599 (0.2%)		1/1054 (0.1%)
Sepsis	0/392 (0%)		1/599 (0.2%)		2/1054 (0.2%)
Urinary tract infection	1/392 (0.3%)		0/599 (0%)		5/1054 (0.5%)
Cellulitis	0/392 (0%)		1/599 (0.2%)		10/1054 (0.9%)
Bronchitis	0/392 (0%)		0/599 (0%)		5/1054 (0.5%)
Diverticulitis	0/392 (0%)		0/599 (0%)		4/1054 (0.4%)
Erysipelas	0/392 (0%)		0/599 (0%)		4/1054 (0.4%)
Pyelonephritis	0/392 (0%)		1/599 (0.2%)		3/1054 (0.3%)
Appendicitis	0/392 (0%)		0/599 (0%)		3/1054 (0.3%)
Arthritis bacterial	0/392 (0%)		0/599 (0%)		3/1054 (0.3%)
Bronchopneumonia	0/392 (0%)		0/599 (0%)		3/1054 (0.3%)
Cystitis	0/392 (0%)		0/599 (0%)		3/1054 (0.3%)
Post procedural infection	0/392 (0%)		0/599 (0%)		3/1054 (0.3%)
Septic shock	0/392 (0%)		1/599 (0.2%)		2/1054 (0.2%)
Upper respiratory tract infection	0/392 (0%)		1/599 (0.2%)		2/1054 (0.2%)
Abdominal wall abscess	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Bursitis infective	0/392 (0%)		1/599 (0.2%)		1/1054 (0.1%)
Staphylococcal device related infection	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Empyema	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Gastroenteritis viral	0/392 (0%)		2/599 (0.3%)		0/1054 (0%)
Herpes zoster	1/392 (0.3%)		0/599 (0%)		1/1054 (0.1%)
Infectious pleural effusion	0/392 (0%)		1/599 (0.2%)		1/1054 (0.1%)
Localised infection	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Lower respiratory tract infection	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Staphylococcal abscess	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Staphylococcal infection	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Staphylococcal sepsis	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Tuberculous pleurisy	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Abdominal abscess	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Abscess soft tissue	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Appendiceal abscess	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Appendicitis perforated	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Breast abscess	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Candida osteomyelitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Cholecystitis infective	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Clostridial infection	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Coccidioidomycosis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Dengue fever	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Endocarditis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Epiglottitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
External ear cellulitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Gallbladder empyema	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Groin abscess	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Hepatitis C	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Infection	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Lung infection	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Meningitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Mycobacterium chelonae infection	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pharyngitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pneumonia bacterial	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pneumonia cryptococcal	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pneumonia legionella	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Prostate infection	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pseudomonas infection	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Respiratory tract infection viral	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Salpingitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Staphylococcal bacteraemia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Systemic candida	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Tubo-ovarian abscess	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Varicella	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Injury, poisoning and procedural complications
Spinal compression fracture	1/392 (0.3%)		0/599 (0%)		3/1054 (0.3%)
Femur fracture	0/392 (0%)		0/599 (0%)		7/1054 (0.7%)
Hip fracture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Lower limb fracture	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Muscle rupture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Tendon rupture	0/392 (0%)		1/599 (0.2%)		2/1054 (0.2%)
Ankle fracture	1/392 (0.3%)		0/599 (0%)		1/1054 (0.1%)
Humerus fracture	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Splenic rupture	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Vascular pseudoaneurysm	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Wound dehiscence	0/392 (0%)		1/599 (0.2%)		1/1054 (0.1%)
Accident	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Alcohol poisoning	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Dislocation of vertebra	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Injury	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Joint injury	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Ligament rupture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Multiple fractures	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Patella fracture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pelvic fracture	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Periprosthetic fracture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Post procedural haemorrhage	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Post procedural stroke	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Procedural complication	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pubis fracture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Radius fracture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Rib fracture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Subdural haematoma	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Synovial rupture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Tibia fracture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Wrist fracture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Investigations
Transaminases increased	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Blood pressure decreased	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Metabolism and nutrition disorders
Hypoglycaemia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Diabetes mellitus	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Dehydration	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Diabetes mellitus inadequate control	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Malnutrition	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/392 (0%)		2/599 (0.3%)		8/1054 (0.8%)
Foot deformity	0/392 (0%)		0/599 (0%)		4/1054 (0.4%)
Intervertebral disc protrusion	1/392 (0.3%)		0/599 (0%)		2/1054 (0.2%)
Intervertebral disc disorder	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Lumbar spinal stenosis	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Osteonecrosis	1/392 (0.3%)		0/599 (0%)		1/1054 (0.1%)
Spinal osteoarthritis	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Intervertebral disc degeneration	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Jaw cyst	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Metatarsalgia	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Muscle disorder	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Osteoporotic fracture	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Rheumatoid arthritis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Spinal column stenosis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Spondylolisthesis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/392 (0.3%)		1/599 (0.2%)		1/1054 (0.1%)
Cardiac myxoma	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Cervix carcinoma stage 0	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Prostate cancer	0/392 (0%)		2/599 (0.3%)		2/1054 (0.2%)
Basal cell carcinoma	0/392 (0%)		2/599 (0.3%)		1/1054 (0.1%)
Breast cancer stage II	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Lung adenocarcinoma metastatic	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Lung adenocarcinoma stage I	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Thyroid cancer	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Uterine leiomyoma	0/392 (0%)		1/599 (0.2%)		1/1054 (0.1%)
Anal cancer	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Benign lung neoplasm	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Bowen's disease	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Cervix carcinoma stage III	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Endometrial cancer	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Endometrial cancer metastatic	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Extranodal marginal zone B-cell lymphoma (malt type)	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Gastrooesophageal cancer	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Large cell carcinoma of the respiratory tract stage unspecified	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Lung squamous cell carcinoma stage III	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Malignant melanoma	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Metastatic malignant melanoma	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Neuroendocrine carcinoma	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Non-small cell lung cancer	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Non-small cell lung cancer metastatic	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Ovarian cancer metastatic	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Parathyroid tumour benign	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Renal cell carcinoma	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Renal cell carcinoma stage I	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Small cell lung cancer metastatic	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Squamous cell carcinoma of skin	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Tongue cancer metastatic	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Transitional cell carcinoma	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Nervous system disorders
Carotid artery occlusion	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Carotid artery stenosis	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Carpal tunnel syndrome	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Presyncope	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Syncope	0/392 (0%)		1/599 (0.2%)		2/1054 (0.2%)
Transient ischaemic attack	1/392 (0.3%)		0/599 (0%)		3/1054 (0.3%)
Cerebrovascular accident	0/392 (0%)		0/599 (0%)		3/1054 (0.3%)
Headache	0/392 (0%)		0/599 (0%)		3/1054 (0.3%)
Encephalitis	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Cerebral atrophy	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Cerebral ischaemia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Convulsion	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Demyelination	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Haemorrhagic stroke	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Hypoglycaemic unconsciousness	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Lumbar radiculopathy	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Myasthenia gravis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Optic neuritis	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Radiculopathy	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Sciatica	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Subarachnoid haemorrhage	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Vasculitis cerebral	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	0/392 (0%)		0/599 (0%)		3/1054 (0.3%)
Abortion spontaneous	1/392 (0.3%)		0/599 (0%)		1/1054 (0.1%)
Psychiatric disorders
Anxiety	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Depression	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Major depression	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Confusional state	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Renal and urinary disorders
Renal colic	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Renal failure	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Calculus ureteric	0/392 (0%)		1/599 (0.2%)		1/1054 (0.1%)
Nephrolithiasis	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Calculus urinary	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Renal failure chronic	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Scleroderma renal crisis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Urinary bladder polyp	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Reproductive system and breast disorders
Metrorrhagia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Cervical dysplasia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Endometriosis	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Ovarian cyst	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Rectocele	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Uterine polyp	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Vaginal haemorrhage	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/392 (0.3%)		0/599 (0%)		1/1054 (0.1%)
Interstitial lung disease	0/392 (0%)		1/599 (0.2%)		1/1054 (0.1%)
Respiratory failure	1/392 (0.3%)		0/599 (0%)		2/1054 (0.2%)
Pulmonary embolism	0/392 (0%)		1/599 (0.2%)		4/1054 (0.4%)
Asthma	0/392 (0%)		1/599 (0.2%)		2/1054 (0.2%)
Chronic obstructive pulmonary disease	0/392 (0%)		0/599 (0%)		2/1054 (0.2%)
Acute interstitial pneumonitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Acute pulmonary oedema	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Atelectasis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Dyspnoea	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Haemothorax	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Organising pneumonia	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pleural fibrosis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pneumothorax	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Pulmonary haemorrhage	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Rheumatoid lung	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Skin and subcutaneous tissue disorders
Angioedema	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Dermatitis allergic	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Digital ulcer	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Generalised erythema	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Ingrowing nail	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Leukocytoclastic vasculitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Palpable purpura	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Skin ulcer	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Urticaria	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Vascular disorders
Wegener's granulomatosis	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Deep vein thrombosis	1/392 (0.3%)		0/599 (0%)		4/1054 (0.4%)
Hypotension	1/392 (0.3%)		0/599 (0%)		0/1054 (0%)
Aortic aneurysm	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Arterial insufficiency	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Diffuse vasculitis	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Femoral artery occlusion	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Hypertension	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Hypertensive crisis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Thrombophlebitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Varicophlebitis	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Vasculitis	0/392 (0%)		1/599 (0.2%)		0/1054 (0%)
Venous insufficiency	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Venous thrombosis limb	0/392 (0%)		0/599 (0%)		1/1054 (0.1%)
Other (Not Including Serious) Adverse Events
	Placebo + Methotrexate		All Tocilizumab 4 mg/kg + Methotrexate		All Tocilizumab 8 mg/kg + Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	169/392 (43.1%)		303/599 (50.6%)		835/1054 (79.2%)
Gastrointestinal disorders
Nausea	18/392 (4.6%)		19/599 (3.2%)		69/1054 (6.5%)
Diarrhoea	10/392 (2.6%)		23/599 (3.8%)		85/1054 (8.1%)
Gastritis	5/392 (1.3%)		18/599 (3%)		73/1054 (6.9%)
Abdominal pain upper	8/392 (2%)		17/599 (2.8%)		53/1054 (5%)
General disorders
Oedema peripheral	8/392 (2%)		10/599 (1.7%)		64/1054 (6.1%)
Infections and infestations
Upper respiratory tract infection	29/392 (7.4%)		55/599 (9.2%)		256/1054 (24.3%)
Urinary tract infection	20/392 (5.1%)		34/599 (5.7%)		170/1054 (16.1%)
Nasopharyngitis	18/392 (4.6%)		30/599 (5%)		123/1054 (11.7%)
Bronchitis	21/392 (5.4%)		32/599 (5.3%)		135/1054 (12.8%)
Influenza	16/392 (4.1%)		19/599 (3.2%)		100/1054 (9.5%)
Sinusitis	10/392 (2.6%)		30/599 (5%)		111/1054 (10.5%)
Pharyngitis	10/392 (2.6%)		23/599 (3.8%)		103/1054 (9.8%)
Gastroenteritis	9/392 (2.3%)		19/599 (3.2%)		82/1054 (7.8%)
Injury, poisoning and procedural complications
Contusion	6/392 (1.5%)		9/599 (1.5%)		55/1054 (5.2%)
Investigations
Transaminases increased	6/392 (1.5%)		29/599 (4.8%)		97/1054 (9.2%)
Alanine aminotransferase increased	5/392 (1.3%)		10/599 (1.7%)		66/1054 (6.3%)
Metabolism and nutrition disorders
Hypercholesterolaemia	3/392 (0.8%)		5/599 (0.8%)		58/1054 (5.5%)
Musculoskeletal and connective tissue disorders
Back pain	9/392 (2.3%)		14/599 (2.3%)		105/1054 (10%)
Arthralgia	8/392 (2%)		10/599 (1.7%)		56/1054 (5.3%)
Rheumatoid arthritis	16/392 (4.1%)		19/599 (3.2%)		99/1054 (9.4%)
Osteoarthritis	4/392 (1%)		4/599 (0.7%)		55/1054 (5.2%)
Nervous system disorders
Headache	8/392 (2%)		25/599 (4.2%)		88/1054 (8.3%)
Psychiatric disorders
Depression	11/392 (2.8%)		12/599 (2%)		60/1054 (5.7%)
Respiratory, thoracic and mediastinal disorders
Cough	12/392 (3.1%)		16/599 (2.7%)		53/1054 (5%)
Vascular disorders
Hypertension	12/392 (3.1%)		34/599 (5.7%)		141/1054 (13.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

Name/Title	Medical Communications
Organization	Hoffmann-La Roche
Phone	800-821-8590
Email

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT00106535

Other Study ID Numbers:

WA17823

First Posted:

Mar 28, 2005

Last Update Posted:

Feb 6, 2014

Last Verified:

Dec 1, 2013