A Study of the Efficacy and Safety of Tocilizumab in Adults With Rheumatoid Arthritis.

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01988012
• Collaborator: (none)
• Enrollment: 100
• Locations: 13
• Arm: 1
• Duration (Months): 17.9
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

A multi-center, open-label single-arm study to evaluate the efficacy and safety of tocilizumab administered as a single, weekly injection in adults with rheumatoid arthritis. Combination therapy with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) was permitted.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Biological: tocilizumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multicenter Study to Evaluate Disease Activity and Safety of Treatment With Actemra (Tocilizumab) Administered as Subcutaneous Injection in Adult RA Patients.
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tocilizumab Adults with rheumatoid arthritis will be treated with tocilizumab for 24 weeks followed by an 8 week follow-up period without treatment.	Biological: tocilizumab; 162 milligram (mg) administered subcutaneously once weekly for 24 weeks; Other Names: RoActemra/Actemra

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity [Week 24]

   Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. Remission is defined as CDAI ≤2.8 and Low Disease Activity (LDA) is defined as 2.8< CDAI ≤10.

2. Change From Baseline in CDAI [Baseline, Week 24]

   Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.

3. Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity [Week 24]

   Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligram/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. An SDAI score of ≤ 3.3 represents clinical remission, a score of ≤ 11.0 represents low disease activity.

4. Change From Baseline in SDAI [Baseline, Week 24]

   Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in mg/L. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A negative change from baseline indicates an improvement.

5. Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR) [Baseline, Week 24]

   The DAS28-ESR score is a measure of the patient's disease activity calculated using the tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), patient's global assessment (PGA) of disease activity based on visual analog scale (VAS) and the erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/hr). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total possible score ranged from 0 to 10. Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.

6. Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70) [Week 24]

   An ACR20 response requires at least 20% improvement compared to baseline in SJC (based on 66 joints) and TJC (based on 68 joints) as well as at least 20% improvement in 3 of the following 5 assessments: 1) PGA pain VAS, 2) PGA VAS; 3) physician's global assessment of disease activity VAS, 4) Health Assessment Questionnaire-Disability Index (HAQ-DI) with 20 questions consisting of 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do; and 5) CRP in mg/L or ESR in mm/hr. ACR50 and ACR70 responses are defined in a similar way except that they required a 50% and 70% improvement from baseline, respectively. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity).

7. Percentage of Participants With Good to Moderate European League Against Rheumatism (EULAR) Response [Week 24]

   Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (</=) 3.2 and reduction of greater than (>) 1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score <=5.1 with reduction of >0.6 to <=1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to <=1.2 points, or any score with reduction <=0.6 points, were assessed as non-responders with response recorded as 'none.'

8. Change From Baseline in TJC and SJC [Baseline, Week 24]

   The number of tender joints (based on 68 joints) and swollen joints (based on 66 joints) were counted at each visit. TJC was determined by identifying the joints that were painful under pressure or to passive motion; no tenderness =0, tenderness =1. SJC was determined by identifying swelling; no swelling =0, swelling =1. A negative change from baseline indicates an improvement.

9. Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy [Baseline, Week 24]

   Participants were either on tocilizumab monotherapy or tocilizumab plus non-biologic disease modifying anti-rheumatic drugs (DMARDs). Reported here is the percentage of participants on tocilizumab monotherapy at baseline and the change from baseline at Week 24. A positive change from baseline at Week 24 indicates the percentage of participants, who discontinued DMARDs during the study.

10. Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS) [Baseline, Week 24]

    PGA VAS represents the participant's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.

11. Change From Baseline in Patient Pain VAS [Baseline, Week 24]

    Patient Pain VAS represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.

12. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) [Baseline, Week 24]

    The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities and 20 questions. Each category contains multiple questions, which were answered using a 4-point scale from 0 (without any difficulty) to 3 (unable to do). The overall index score was an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. A negative change from baseline indicates an improvement.

13. Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) [Baseline, Week 24]

    The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 52. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. A positive change from baseline indicates an improvement.

14. Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) [Baseline, Week 24]

    The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. HAS is a clinician-administered assessment to measure the severity of anxiety symptoms and consists of 14 items with a total score range from 0 to 56. A higher score indicates a worse outcome.

Secondary Outcome Measures

1. Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs) [Up to Follow-up Week 32]

   An AE is any untoward medical occurrence in a participant administered a drug and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not considered related to the drug. Preexisting conditions which worsen during a study are also considered as AEs. AESIs are AEs that occur in categories of special interest with regard to the benefit-risk profile and overall safety of a drug. The following nine categories of AESIs were identified for tocilizumab: 1) serious and/or medically significant infections, 2) myocardial infarction/acute coronary syndrome, 3) gastrointestinal perforations, 4) malignancies, 5) anaphylaxis/hypersensitivity reactions, 6) demyelinating disorders, 7) stroke, 8) serious and/or medically significant bleeding events, and 9) serious and/or medically significant hepatic events.

2. Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs [Up to Week 24]

3. Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies [Baseline, Week 24, Follow-up Week 32 and Early Withdrawal]

   Reported is the percentage of participants positive for anti-tocilizumab antibodies in the confirmatory anti-tocilizumab antibody assay, which followed an initial anti-tocilizumab screen. Participants, who withdrew from the study

4. Immunogenicity: Tocilizumab Levels [Week 12, Week 24, Follow-up Week 32 and Early Withdrawal]

5. Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels [Week 1, Week 12, Week 24, Follow-up Week 32 and Early Withdrawal]

   A positive change from Week 1 indicates an increase in sIL-6R levels.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adults >/= 18 years of age

• Diagnosis of active rheumatoid arthritis (RA) according to the revised (1987) American College of Rheumatology (ACR) criteria or European League Against Rheumatism (EULAR)/ACR (2010) criteria

• Previously treated with the following: three non-biologic DMARDs, and not treated with any biologic agent OR one biologic agent (alone or in combination with non-biologic DMARDs), and discontinued that agent for a reason

• Oral corticosteroids (</= 10 mg/day prednisone or equivalent), non-steroidal anti-inflammatory drug (NSAIDs) and non-biologic DMARDs are permitted if on a stable dose regimen for >/= 4 weeks prior to Baseline

• Use of effective contraception throughout the study as defined by protocol; female patients of childbearing potential must not be pregnant

Exclusion Criteria:

• Presence of serious, uncontrolled, clinically significant medical conditions

• History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal (GI) disease that might predispose to perforation

• Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections

• Any infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening

• Clinically significant findings on lab tests and/or hepatitis B or C, or human immunodeficiency virus (HIV) screenings

• Active tuberculosis (TB) requiring treatments within the previous 3 years

• Evidence of active malignant disease, malignancies diagnosed within the previous 10 years, or breast cancer diagnosed within the previous 20 years

• History of alcohol, drug, or chemical abuse within 1 year prior to Screening

• Neuropathies or other conditions that might interfere with pain evaluation

• Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 6 months following Baseline

• Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Secondary Sjögren's syndrome with RA is permitted

• Functional Class IV as defined by the ACR Classification of Functional Status in-Rheumatoid Arthritis

• Diagnosis of juvenile idiopathic arthritis or juvenile RA, and/or RA before the age of 16

• Prior history of current inflammatory joint disease other than RA

• Exposure to tocilizumab (either IV or subcutaneous administration) at any time prior to Baseline

• Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening

• Previous treatment with any cell-depleting therapies, including investigational agents approved therapies, with alkylating agents such as chlorambucil, or with total lymphoid irradiation

• Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline

• Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Beer Sheva		Israel	8410101
2		Beer Yaacov		Israel	6093000
3		Haifa		Israel	3109601
4		Haifa		Israel	3339419
5		Haifa		Israel	34362
6		Jerusalem		Israel	9112001
7		Jerusalem		Israel	91240
8		Kfar Saba		Israel	44281
9		Petach Tikva		Israel	4937211
10		Petach Tikva		Israel	4941492
11		Ramat Gan		Israel	5262000
12		Ramat Gan		Israel	5262100
13		Tel Aviv		Israel	6423906

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: NCT01988012
• Other Study ID Numbers: ML28698
• First Posted: Nov 20, 2013
• Last Update Posted: Mar 6, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 milligram (mg) tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Period Title: Overall Study
STARTED	100
COMPLETED	85
NOT COMPLETED	15

Baseline Characteristics

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Overall Participants	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.3 (11.8)
Gender (Count of Participants)
Female	80 80%
Male	20 20%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity
Description	Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. Remission is defined as CDAI ≤2.8 and Low Disease Activity (LDA) is defined as 2.8< CDAI ≤10.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The analysis population included those participants from the full analysis set (FAS) for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	85
CDAI Remission	16.5 16.5%
CDAI LDA	34.1 34.1%

2. Primary Outcome

Title	Change From Baseline in CDAI
Description	Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	100
Baseline	31.89 (14.35)
Change from Baseline at Week 24	-18.29 (14.52)

3. Primary Outcome

Title	Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity
Description	Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligram/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. An SDAI score of ≤ 3.3 represents clinical remission, a score of ≤ 11.0 represents low disease activity.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	52
SDAI Remission	19.2 19.2%
SDAI LDA	38.5 38.5%

4. Primary Outcome

Title	Change From Baseline in SDAI
Description	Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in mg/L. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A negative change from baseline indicates an improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	98
Baseline	33.73 (14.83)
Change from Baseline at Week 24	-21.41 (14.99)

5. Primary Outcome

Title	Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR)
Description	The DAS28-ESR score is a measure of the patient's disease activity calculated using the tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), patient's global assessment (PGA) of disease activity based on visual analog scale (VAS) and the erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/hr). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total possible score ranged from 0 to 10. Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	99
Baseline	4.98 (0.98)
Change from Baseline at Week 24	-2.47 (1.29)

6. Primary Outcome

Title	Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70)
Description	An ACR20 response requires at least 20% improvement compared to baseline in SJC (based on 66 joints) and TJC (based on 68 joints) as well as at least 20% improvement in 3 of the following 5 assessments: 1) PGA pain VAS, 2) PGA VAS; 3) physician's global assessment of disease activity VAS, 4) Health Assessment Questionnaire-Disability Index (HAQ-DI) with 20 questions consisting of 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do; and 5) CRP in mg/L or ESR in mm/hr. ACR50 and ACR70 responses are defined in a similar way except that they required a 50% and 70% improvement from baseline, respectively. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	85
ACR20	62.4 62.4%
ACR50	37.6 37.6%
ACR70	20.0 20%

7. Primary Outcome

Title	Percentage of Participants With Good to Moderate European League Against Rheumatism (EULAR) Response
Description	Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (</=) 3.2 and reduction of greater than (>) 1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score <=5.1 with reduction of >0.6 to <=1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to <=1.2 points, or any score with reduction <=0.6 points, were assessed as non-responders with response recorded as 'none.'
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	83
Number [percentage of participants]	96.4 96.4%

8. Primary Outcome

Title	Change From Baseline in TJC and SJC
Description	The number of tender joints (based on 68 joints) and swollen joints (based on 66 joints) were counted at each visit. TJC was determined by identifying the joints that were painful under pressure or to passive motion; no tenderness =0, tenderness =1. SJC was determined by identifying swelling; no swelling =0, swelling =1. A negative change from baseline indicates an improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	100
TJC at Baseline	21.42 (15.20)
TJC Change from Baseline at Week 24	-11.91 (13.59)
SJC at Baseline	10.30 (10.27)
SJC Change from Baseline at Week 24	-7.54 (9.60)

9. Primary Outcome

Title	Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy
Description	Participants were either on tocilizumab monotherapy or tocilizumab plus non-biologic disease modifying anti-rheumatic drugs (DMARDs). Reported here is the percentage of participants on tocilizumab monotherapy at baseline and the change from baseline at Week 24. A positive change from baseline at Week 24 indicates the percentage of participants, who discontinued DMARDs during the study.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	100
Baseline	26 26%
Change from Baseline at Week 24	12 12%

10. Primary Outcome

Title	Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS)
Description	PGA VAS represents the participant's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	100
Baseline	69.73 (24.55)
Change from Baseline at Week 24	-31.22 (28.43)

11. Primary Outcome

Title	Change From Baseline in Patient Pain VAS
Description	Patient Pain VAS represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	100
Baseline	64.82 (26.39)
Change from Baseline at Week 24	-29.11 (29.16)

12. Primary Outcome

Title	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
Description	The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities and 20 questions. Each category contains multiple questions, which were answered using a 4-point scale from 0 (without any difficulty) to 3 (unable to do). The overall index score was an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. A negative change from baseline indicates an improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	100
Baseline	1.55 (0.80)
Change from Baseline at Week 24	-0.34 (0.62)

13. Primary Outcome

Title	Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
Description	The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 52. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. A positive change from baseline indicates an improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	100
Baseline	23.46 (11.32)
Change from Baseline at Week 24	6.95 (9.70)

14. Primary Outcome

Title	Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS)
Description	The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. HAS is a clinician-administered assessment to measure the severity of anxiety symptoms and consists of 14 items with a total score range from 0 to 56. A higher score indicates a worse outcome.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	100
HDRS at Baseline	7.87 (7.19)
HDRS at Week 24	4.94 (5.85)
HAS at Baseline	8.56 (8.43)
HAS at Week 24	5.93 (7.17)

15. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs)
Description	An AE is any untoward medical occurrence in a participant administered a drug and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not considered related to the drug. Preexisting conditions which worsen during a study are also considered as AEs. AESIs are AEs that occur in categories of special interest with regard to the benefit-risk profile and overall safety of a drug. The following nine categories of AESIs were identified for tocilizumab: 1) serious and/or medically significant infections, 2) myocardial infarction/acute coronary syndrome, 3) gastrointestinal perforations, 4) malignancies, 5) anaphylaxis/hypersensitivity reactions, 6) demyelinating disorders, 7) stroke, 8) serious and/or medically significant bleeding events, and 9) serious and/or medically significant hepatic events.
Time Frame	Up to Follow-up Week 32

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	100
AEs	70.0 70%
AESIs	7.0 7%

16. Secondary Outcome

Title	Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	100
% of Particpants with Dose Modifications	16 16%
% of Participants Who Discontinued Study	5 5%

17. Secondary Outcome

Title	Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies
Description	Reported is the percentage of participants positive for anti-tocilizumab antibodies in the confirmatory anti-tocilizumab antibody assay, which followed an initial anti-tocilizumab screen. Participants, who withdrew from the study
Time Frame	Baseline, Week 24, Follow-up Week 32 and Early Withdrawal

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	97
Baseline	1.0 1%
Week 24	0 0%
Follow-up Visit Week 32	0 0%
Early Withdrawal	0 0%

18. Secondary Outcome

Title	Immunogenicity: Tocilizumab Levels
Time Frame	Week 12, Week 24, Follow-up Week 32 and Early Withdrawal

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	91
Week 12	35.49 (17.81)
Week 24	41.63 (22.79)
Follow-up Week 32	39.53 (28.47)
Early withdrawal	19.04 (15.69)

19. Secondary Outcome

Title	Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels
Description	A positive change from Week 1 indicates an increase in sIL-6R levels.
Time Frame	Week 1, Week 12, Week 24, Follow-up Week 32 and Early Withdrawal

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Measure Participants	98
Week 1	38.33 (10.30)
Change from Week 1 at Week 12	475.79 (120.98)
Change from Week 1 at Week 24	503.67 (127.13)
Change from Week 1 at Follow-up at Week 32	382.26 (240.95)
Change from Week 1 at Early withdrawal	309.91 (183.07)

Adverse Events

Time Frame	Up to Follow-up Week 32
Adverse Event Reporting Description	The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
Arm/Group Title	Tocilizumab
Arm/Group Description	Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
All Cause Mortality
	Tocilizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tocilizumab
	Affected / at Risk (%)	# Events
Total	6/100 (6%)
Gastrointestinal disorders
Colitis	1/100 (1%)
General disorders
Chest pain	1/100 (1%)
Infections and infestations
Cellulitis	1/100 (1%)
Reproductive system and breast disorders
Adnexal torsion	1/100 (1%)
Skin and subcutaneous tissue disorders
Urticaria	1/100 (1%)
Vascular disorders
Haematoma	1/100 (1%)
Other (Not Including Serious) Adverse Events
	Tocilizumab
	Affected / at Risk (%)	# Events
Total	44/100 (44%)
Blood and lymphatic system disorders
Leukopenia	11/100 (11%)
Neutropenia	12/100 (12%)
Infections and infestations
Upper respiratory tract infection	7/100 (7%)
Urinary tract infection	7/100 (7%)
Investigations
Alanine aminotransferase increased	8/100 (8%)
Aspartate aminotransferase increased	6/100 (6%)
Hepatic enzyme increased	11/100 (11%)

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.