ARMONIA: An Observational Study of Biologic Drugs in Monotherapy or Combination With DMARDs in Italian Clinical Practice and the Efficacy and Safety of RoActemra/Actemra (Tocilizumab) Monotherapy in Patients With Rheumatoid Arthritis

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01791205

Collaborator

(none)

304

Enrollment

Locations

Duration (Months)

10.9

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multicenter observational study in patients with rheumatoid arthritis in routine clinical practice in Italy. In the retrospective Part 1 of the study, clinical and demographic factors associated with the use of a biologic drug in monotherapy as compared to therapy in combination with Disease-modifying anti-rheumatic drugs (DMARDs) will be evaluated. In the retrospective/prospective Part 2 of the study, efficacy and safety of the use of RoActemra/Actemra (tocilizumab) in monotherapy will be evaluated. Patients will be followed for up to18 months.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis

Study Design

Study Type:

Observational

Actual Enrollment :

304 participants

Observational Model:

Cohort

Official Title:

A Multi-Center Observational Study on the Use of Biologic Drugs as Monotherapy or Combination With DMARDs in Patients With Rheumatoid Arthritis in Italian Clinical Practice (ARMONIA)

Study Start Date :

May 1, 2013

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Monotherapy Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry will be observed for Phase I. Participants who were enrolled in Phase I and received tocilizumab (TCZ) as a monotherapy will be observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Combination Therapy Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry will be observed for Phase I.

Arm

Intervention/Treatment

Monotherapy

Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry will be observed for Phase I. Participants who were enrolled in Phase I and received tocilizumab (TCZ) as a monotherapy will be observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.

Combination Therapy

Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry will be observed for Phase I.

Outcome Measures

Primary Outcome Measures

Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
Demographic characteristics were analyzed in participants at Baseline, where Baseline is considered as the study entry visit (day of informed consent form signed). Demographic characteristics which were taken into account included age in years, race, height in centimeters (cm), weight in Kilograms (Kg), and Body Mass Index (BMI) in Kg/cm^2. Participants with age =<, > 59 years, height =<, > 163 cm, weight =<, > 65.85 Kg and BMI =<, > 24.98 Kg/cm^2 are reported.
Phase I: Number of Participants With Disease Duration in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The duration of disease is defined as the total time from the diagnosis of rheumatoid arthritis (RA) until the study entry.
Phase I: Number of Participants With Comorbidity in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
Comorbidity is the presence of previous or concomitant diseases.
Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The autoantibody included seropositive or seronegative participants for rheumatoid factor (RF) and/or anti-cyclic citrullinated protein antibodies (Anti-CCP). RF value higher than 20 Units (U)/milliliter (mL) is considered seropositive and anti-CCP antibodies value higher than 10 U/mL is considered positive.
Phase I: Number of Participants With Health Assessment Questionnaire- Disability Index in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The Health Assessment Questionnaire- Disability Index (HAQ-DI) is a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatoid arthritis. It consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity. Participants assessed their ability to do each task over the past seven days. Participants with scores =< 0.8625 and > 0.8625 are reported.
Phase I: Number of Participants With Disease Activity Score 28 in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The disease activity included Disease Activity Score 28 (DAS28). The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen joint counts (SJC) and tender joint counts (TJC), acute phase response, and general health status. The DAS28 scale ranges from 0 to 10 (0= no disease activity and 10= maximum disease activity; where higher scores represents higher disease activity. The DAS =< 2.8 indicates clinical remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high disease activity. Participants with DAS28 score =< 2.6 and > 2.6 are reported.
Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The disease activity included biological markers of inflammation: C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR). A reduction in CRP and ESR values indicates improvement. Participants with CRP values =< 0.28 and >2.8 milligram/deciliter (mg/dL); and ESR values =< 11 and >11 millimeters/hour (mm/hr) are reported.
Phase I: Number of Participants With Clinical Disease Activity Index in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The disease activity included Clinical Disease Activity Index (CDAI) which is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment; and patient's global assessment (PtGA) and physician's global assessment (PhGA) assessed on 0-10 cm visual analog scale (VAS), where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =< 2.8 indicates clinical remission, > 2.8 to 10 indicates low disease activity, > 10 to 22 indicates moderate disease activity, and > 22 indicates high disease activity. Participants with CDAI score =< 7.75 and > 7.75 are reported.
Phase I: Number of Participants With Simplified Disease Activity Index in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The disease activity included Simplified Disease Activity Index (SDAI) which is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity. Participants with SDAI score =< 8.17 and > 8.17 are reported.
Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The duration of combination therapy before monotherapy are reported. The duration was estimated by calculating total duration from starting the combination therapy till the participant switched to monotherapy. Participants who started the combination therapy and later switched to monotherapy =< 337 days, > 337 days, =< 336 days, > 336 days are reported.
Phase I: Number of Participants Treatment Line in Which Monotherapy Has Been Adopted in Monotherapy [At Baseline (Day of informed consent form signed)]
The first biologic treatment line was defined as the first use of any biologic drug in treatment of rheumatoid arthritis, regardless its association with DMARDs and the second treatment line as the subsequent use of a different biologic drug. Participants who adopted monotherapy as =< 2 and > 2 therapy lines are reported. According to the study protocol objectives, this analysis was performed only for Monotherapy arm.
Phase I: Number of Biologics Administered as Monotherapy in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
Participants who received at least one previous treatment with biologics in monotherapy and no previous monotherapy with biologics are reported.
Phase I: Number of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
Participants who had prevalence with at least one previous switch, swaps, and switch/swap to other therapy are reported.
Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy [At Baseline (Day of informed consent form signed)]
Reasons leading to the use of biologic in monotherapy includes DMARDs intolerance, insufficient therapeutic effect, intolerance to biologic drug, low participant's compliance, concomitant pathologies, pregnancy desire, remission from combination therapy, remission from monotherapy, others and unknown. Participants with reason leading to the use of biologic in monotherapy are presented. According to the study protocol objectives, this analysis was performed only for Monotherapy arm.
Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy [Up to 18 months]
The probabilities of participant to retain on therapy at various time points are reported.
Phase II: Retention Rate in Therapy, Percentage of Participants Achieving DAS 28 ESR <2.6 and <3.2 at Month 18 [At month 18]
Participants who retained the therapy were analyzed for disease activity (DAS28 ESR) at Month 18. The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease.

Secondary Outcome Measures

Phase I: Median Disease Duration in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The duration of disease is defined as the total time from the diagnosis of RA until the study entry.
Phase I: Percentage of Participants With Comorbidity in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
Comorbidity is the presence of previous or concomitant diseases. Percentage of participants with comorbidity is reported.
Phase I: Mean Health Assessment Questionnaire-Disability Index in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The HAQ-DI is a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatoid arthritis. It consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity. Participants assessed their ability to do each task over the past seven days.
Phase I: Percentage of Participants Who Started Treatment With a Biologic Drug in Monotherapy and Percentage of Participants Who Stopped a DMARDs While Taking a Biologic Drug in Combination Therapy [At Baseline (Day of informed consent form signed)]
The table below shows percentage participants who started treatment with a biologic drug in monotherapy compared with percentage of participants who stopped DMARDs while taking a biologic drug in combination.
Phase I: Number of Participants Receiving a Biologic Drug as Monotherapy at Different Treatment Lines [At Baseline (Day of informed consent form signed)]
The first biologic treatment line was defined as the first use of any biologic drug in treatment of rheumatoid arthritis, regardless its association with DMARDs, the second treatment line as the subsequent use of a different biologic drug and so on for the third, fourth, fifth and sixth treatment line. According to the study protocol objectives, this analysis was performed only for Monotherapy arm.
Phase I: Number of Participants With at Least One Previous Treatment With Biologics Drug as a Monotherapy in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
Number of participants who received at least one previous treatment with a biologic drug as a monotherapy in both groups is reported.
Phase I: Percentage of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
Participants who had prevalence with at least one previous switch, swaps or switch/swap to other therapy either monotherapy or combination therapy are reported.
Phase I: Median DAS28 at Study Entry in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The DAS28 is a combined index for measuring disease activity in RA. The index includes SJC and TJC, acute phase response, and general health status. The DAS28 scale ranges from 0 to 10 (0= no disease activity and 10= maximum disease activity) where higher scores represents higher disease. The DAS28 <2.6 indicates disease remission, >=2.6 and <3.2 indicates Low disease activity, >=3.2 and <=5.1 indicates Moderate disease activity and >5.1 indicates High disease activity. Median score for DAS28 at the study entry (Baseline) is reported.
Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment; and PtGA and PhGA assessed on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =< 2.8 indicates clinical remission, > 2.8 to 10 indicates low disease activity, > 10 to 22 indicates moderate disease activity, and > 22 indicates high disease activity. Number of participants with CDAI scores for both the groups at study entry (baseline) are reported.
Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (assessed on 0-10 cm) VAS; 0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
Phase I: Mean Tender Joints and Swollen Joints as Disease Activity at Study Entry in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
Mean of tender and swollen joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender and swollen joints was recorded on the joint assessment as no tenderness = 0 and tenderness = 1.
Phase I: Percentage of Participants Treated With Corticosteroids at Study Entry in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
The percentage of participants treated with corticosteroids at enrollment is reported.
Phase I: Mean Dose of Corticosteroids At Study Entry in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
Mean dose of corticosteroids at study entry (Baseline) is reported.
Phase I: Mean Duration of Previous Treatment With a Biologic Drug in Monotherapy and Combination Therapy [At Baseline (Day of informed consent form signed)]
Mean duration of previous treatment with a biologic drug in monotherapy are reported.
Phase I: Mean Duration of Treatment With A Biologic Drug in Combination With DMARDs Before Monotherapy [At Baseline (Day of informed consent form signed)]
Mean duration of treatment with a biologic drug in combination with DMARDs before monotherapy is reported in days.
Phase II: Percentage of Participants Maintaining Delta DAS 28 CRP of >= 0.6 at Months 3, 6, 12, and 18 [At Months 3, 6, 12, and 18]
Participants who maintained the change in DAS28 (Delta DAS28) CRP of >=0.6 after 3, 6, 12, and 18 months from the first infusion with tocilizumab as monotherapy are reported. The DAS28-CRP is a combined index that measured RA disease activity. It is calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). It is calculated by using the formula: DAS28 CRP= 0.56 × square root of TJC 28 + 0.28 square root of SJC 28 + 0.36 × log n at (CRP+1) + 0.014 × PtGA + 0.96. The DAS28 CRP- scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease.
Phase II: Percentage of Participants Maintaining Delta DAS28 ESR >= 0.6 at Months 3, 6, 12, and 18 [At Months 3, 6, 12, and 18]
Participants who maintained delta DAS28 ESR of >= 0.6 after 3, 6, 12, and 18 months from the first infusion with tocilizumab as monotherapy are reported. The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); where decrease in score indicated improvement of disease.
Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 [At Months 3, 6, 12, and 18]
The DAS28-CRP is a combined index that measured RA disease activity. It is calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). It is calculated by using the formula: DAS28 CRP= 0.56 × square root of TJC (28 joints) + 0.28 square root of SJC (28 joints) + 0.36 × log n at (CRP+1) + 0.014 × PtGA + 0.96. The DAS28 CRP scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease. The DAS28 CRP < 2.6 indicates disease remission and >=2.6 to 3.2 indicates low disease activity.
Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 [At Months 3, 6, 12, and 18]
The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease. The DAS28 ESR < 2.6 indicates disease remission and >=2.6 to 3.2 indicates low disease activity.
Phase II: Percentage of Participants Achieving CDAI Remission (< 2.8) at Months 3, 6, 12, and 18 [At Months 3, 6, 12, and 18]
Percentage of participants achieving CDAI remission < 2.8, after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy are reported. CDAI is the numerical sum of four outcome parameters: TJC, SJC based on a 28-joint assessment; and PtGA and PhGA assessed on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =< 2.8 indicates clinical remission, > 2.8 to 10 indicates low disease activity, > 10 to 22 indicates moderate disease activity, and > 22 indicates high disease activity.
Phase II: Percentage of Participant Achieving SDAI Remission (< 3.3) at Months 3, 6, 12, and 18 [At Months 3, 6, 12, and 18]
Percentage of participant achieving SDAI remission (< 3.3), after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy is reported. The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA which (based on 0-10 cm VAS, 0 = no disease activity and 10 = worst disease activity, where higher scores represent higher disease activity), and CRP. The SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity.
Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18 [From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18]
The mean change from Baseline (day of the first infusion with tocilizumab as monotherapy) in the TJC And SJC after 3, 6, 12 and 18 months is reported. The TJC and SJC were determined for 28 joint counts. The scores ranged from 0 (no disease activity) to 28 (higher/worsen disease activity), where higher scores represents higher disease activity.
Phase II: Mean Change From Baseline in Dose of Corticosteroids at Months 3, 6, 12, and 18 [From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18]
Mean Change From Baseline (day of the first infusion with tocilizumab as monotherapy) in the dose of corticosteroids after 3, 6, 12 and 18 months from Baseline is reported.
Phase II: Percentage of Participants With Delta HAQ >= 0.21 at Months 3, 6, 12, and 18 [At Months 3, 6, 12, and 18]
Percentage of participants with change in HAQ (Delta HAQ) of >= 0.21 after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy are reported. The HAQ consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity.
Phase II: Mean VAS Fatigue Score Overtime [At Baseline (Day of first administration of TCZ as a monotherapy) and Months 3, 6, 12, and 18]
The VAS fatigue score ranging from 0 (symptom-free and no arthritis symptoms) to 100 (worsening in symptoms and arthritis disease activity). Higher score indicate worsening.
Phase II: Number of Participants With Any Adverse Events, Any Serious Adverse Events, Adverse Events of Special Interest, and Tubercular Events [Up to 18 months]
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AE. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death is life threatening, requires hospitalization or prolongation of hospitalization, or results in disability/incapacity, or congenital anomaly/birth defect. The AE were captured only for Phase II.
Phase II: Number of Participants With Retention in Therapy Without Interruption Due to Side Effects [Up to 18 months]
Number of participants who retained in therapy without interruption due to side effects is reported.
Phase II: Number of Side Effects That Had Not Induced Discontinuation of Treatment [Up to 18 months]
Number of side effects (AEs) that had not induced discontinuation of treatment is reported. The AEs were captured only for Phase II.
Phase II: Number of Side Effects That Induced Transient Interruption of Treatment [Up to 18 months]
Number of side effects (AEs) that induced transient interruption of treatment is reported. The AEs were captured only for Phase II.
Phase II: Mean Change From Baseline in Hemoglobin Levels Over Time [From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18]
The mean change in hemoglobin concentration was calculated by subtracting the baseline hemoglobin concentration from the monthly hemoglobin concentration is reported.
Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time [From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18]
Mean Change from Baseline in hematocrit, neutrophils, eosinophils, basophils, lymphocytes, monocytes are reported.
Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time [From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18]
Mean change from baseline in red blood cells (RBC), white blood cells (WBC) and platelets are reported.
Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time [From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18]
Mean change from baseline in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), total bilirubin, direct bilirubin, glucose, creatinine, blood urea nitrogen (BUN) levels are reported.
Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time [From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18]
Mean change from baseline in aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase levels are reported.
Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time [From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18]
Serum electrophoresis parameters includes albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, gamma globulin was reported. Mean change from Baseline values are reported at each time points.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Part 1:

Adult patients, >/= 18 years of age
Diagnosis of rheumatoid arthritis according to American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria
Patients who received at least one cycle of biologic therapy, either in monotherapy or in combination, in the 12 months preceding the opening of the first site

Part 2:

Patients on monotherapy with RoActemra/Actemra already enrolled in Part 1 of the study

Exclusion Criteria:

Patients simultaneously participating in other studies with RoActemra/Actemra at the time of signing informed consent

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Reggio Calabria	Calabria	Italy	89133
2	Napoli	Campania	Italy	80131
3	Telese Terme	Campania	Italy	82037
4	Bologna	Emilia-Romagna	Italy	40138
5	Roma	Lazio	Italy	00133
6	Roma	Lazio	Italy	00152
7	Roma	Lazio	Italy	00161
8	Roma	Lazio	Italy	00189
9	Legnano	Lombardia	Italy	20025
10	Milano	Lombardia	Italy	20157
11	Milano	Lombardia	Italy	20162
12	Monza	Lombardia	Italy	20052
13	Pavia	Lombardia	Italy	27100
14	Ancona	Marche	Italy	60020
15	Jesi	Marche	Italy	60035
16	Torino	Piemonte	Italy	10126
17	Torino	Piemonte	Italy	10128
18	Bari	Puglia	Italy	70124
19	Martina Franca	Puglia	Italy	74015
20	Sassari	Sardegna	Italy	07100
21	Firenze	Toscana	Italy	50139
22	Pisa	Toscana	Italy	56100
23	Prato	Toscana	Italy	59100
24	Siena	Toscana	Italy	53100
25	Perugia	Umbria	Italy	06122
26	Cona (Ferrara)	Veneto	Italy	44124
27	Padova	Veneto	Italy	35128
28	Verona	Veneto	Italy	37126

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:

NCT01791205

Other Study ID Numbers:

ML28552

First Posted:

Feb 13, 2013

Last Update Posted:

Jan 10, 2017

Last Verified:

Nov 1, 2016

Additional relevant MeSH terms:

Arthritis

Arthritis, Rheumatoid

Study Results

Participant Flow

Recruitment Details	A total of 304 participants were enrolled in the study conducted from May 2013 to October 2014 at 29 centers in Italy.
Pre-assignment Detail

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received tocilizumab (TCZ) as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Period Title: Phase I
STARTED	152	152
COMPLETED	152	152
NOT COMPLETED	0	0
Period Title: Phase I
STARTED	104	0
COMPLETED	92	0
NOT COMPLETED	12	0

Baseline Characteristics

Arm/Group Title	Monotherapy	Combination Therapy	Total
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.	Total of all reporting groups
Overall Participants	152	152	304
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.4 (12.5)	59.4 (10.9)	58.4 (11.8)
Gender (Count of Participants)
Female	130 85.5%	127 83.6%	257 84.5%
Male	22 14.5%	25 16.4%	47 15.5%

Outcome Measures

1. Primary Outcome

Title	Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy
Description	Demographic characteristics were analyzed in participants at Baseline, where Baseline is considered as the study entry visit (day of informed consent form signed). Demographic characteristics which were taken into account included age in years, race, height in centimeters (cm), weight in Kilograms (Kg), and Body Mass Index (BMI) in Kg/cm^2. Participants with age =<, > 59 years, height =<, > 163 cm, weight =<, > 65.85 Kg and BMI =<, > 24.98 Kg/cm^2 are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	152	152
Age =< 59 years (n= 152, 152)	79 52%	75 49.3%
Age > 59 years (n= 152, 152)	73 48%	77 50.7%
Race Caucasian (n= 152, 152)	152 100%	150 98.7%
Height =< 163 cm (n= 149, 150)	81 53.3%	69 45.4%
Height >163 cm (n= 149, 150)	68 44.7%	81 53.3%
Weight =< 65.85 Kg (n= 152, 152)	84 55.3%	68 44.7%
Weight > 65.85 Kg, (n= 152, 152)	68 44.7%	84 55.3%
BMI =< 24.98 Kg/cm^2 (n= 149, 150)	77 50.7%	74 48.7%
BMI > 24.98 Kg/cm^2 (n= 149, 150)	72 47.4%	76 50%

2. Primary Outcome

Title	Phase I: Number of Participants With Disease Duration in Monotherapy and Combination Therapy
Description	The duration of disease is defined as the total time from the diagnosis of rheumatoid arthritis (RA) until the study entry.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	152	152
Duration of disease =< 124 months	74 48.7%	81 53.3%
Duration of disease > 124 months	78 51.3%	71 46.7%

3. Primary Outcome

Title	Phase I: Number of Participants With Comorbidity in Monotherapy and Combination Therapy
Description	Comorbidity is the presence of previous or concomitant diseases.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	152	152
Number [Participants]	121 79.6%	116 76.3%

4. Primary Outcome

Title	Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy
Description	The autoantibody included seropositive or seronegative participants for rheumatoid factor (RF) and/or anti-cyclic citrullinated protein antibodies (Anti-CCP). RF value higher than 20 Units (U)/milliliter (mL) is considered seropositive and anti-CCP antibodies value higher than 10 U/mL is considered positive.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	128	128
RF Positive (n= 128, 128)	69 45.4%	79 52%
RF Negative (n= 128, 128)	59 38.8%	49 32.2%
Anti-CCP Positive (n= 100, 103)	61 40.1%	72 47.4%
Anti-CCP Negative (n= 100, 103)	39 25.7%	31 20.4%

5. Primary Outcome

Title	Phase I: Number of Participants With Health Assessment Questionnaire- Disability Index in Monotherapy and Combination Therapy
Description	The Health Assessment Questionnaire- Disability Index (HAQ-DI) is a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatoid arthritis. It consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity. Participants assessed their ability to do each task over the past seven days. Participants with scores =< 0.8625 and > 0.8625 are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available data at the time of evaluation are reported.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	84	80
HAQ-DI Score =< 0.8625	42 27.6%	40 26.3%
HAQ-DI Score >0.8625	42 27.6%	40 26.3%

6. Primary Outcome

Title	Phase I: Number of Participants With Disease Activity Score 28 in Monotherapy and Combination Therapy
Description	The disease activity included Disease Activity Score 28 (DAS28). The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen joint counts (SJC) and tender joint counts (TJC), acute phase response, and general health status. The DAS28 scale ranges from 0 to 10 (0= no disease activity and 10= maximum disease activity; where higher scores represents higher disease activity. The DAS =< 2.8 indicates clinical remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high disease activity. Participants with DAS28 score =< 2.6 and > 2.6 are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available data at Baseline are reported.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	121	122
DAS28 with =< 2.6 score	67 44.1%	55 36.2%
DAS28 with >2.6 score	54 35.5%	67 44.1%

7. Primary Outcome

Title	Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy
Description	The disease activity included biological markers of inflammation: C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR). A reduction in CRP and ESR values indicates improvement. Participants with CRP values =< 0.28 and >2.8 milligram/deciliter (mg/dL); and ESR values =< 11 and >11 millimeters/hour (mm/hr) are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available data at Baseline are reported. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	135	136
CRP =< 0.28 mg/dL (n= 128, 129)	66 43.4%	64 42.1%
CRP > 0.28 mg/dL (n= 128, 129)	62 40.8%	65 42.8%
ESR =< 11 mm/h (n= 135, 136)	80 52.6%	59 38.8%
ESR > 11 mm/h (n= 135, 136)	55 36.2%	77 50.7%

8. Primary Outcome

Title	Phase I: Number of Participants With Clinical Disease Activity Index in Monotherapy and Combination Therapy
Description	The disease activity included Clinical Disease Activity Index (CDAI) which is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment; and patient's global assessment (PtGA) and physician's global assessment (PhGA) assessed on 0-10 cm visual analog scale (VAS), where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =< 2.8 indicates clinical remission, > 2.8 to 10 indicates low disease activity, > 10 to 22 indicates moderate disease activity, and > 22 indicates high disease activity. Participants with CDAI score =< 7.75 and > 7.75 are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available data at Baseline are reported.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	74	77
CDAI Score =< 7.75	37 24.3%	39 25.7%
CDAI Score > 7.75	37 24.3%	38 25%

9. Primary Outcome

Title	Phase I: Number of Participants With Simplified Disease Activity Index in Monotherapy and Combination Therapy
Description	The disease activity included Simplified Disease Activity Index (SDAI) which is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity. Participants with SDAI score =< 8.17 and > 8.17 are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available data at Baseline are reported.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	72	69
SDAI Score =< 8.17	36 23.7%	35 23%
SDAI Score > 8.17	36 23.7%	34 22.4%

10. Primary Outcome

Title	Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy
Description	The duration of combination therapy before monotherapy are reported. The duration was estimated by calculating total duration from starting the combination therapy till the participant switched to monotherapy. Participants who started the combination therapy and later switched to monotherapy =< 337 days, > 337 days, =< 336 days, > 336 days are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	81	74
Duration of combination type 1, =< 337 (n= 81, 74)	45 29.6%	33 21.7%
Duration of combination type 1, > 337 (n= 81, 74)	36 23.7%	41 27%
Duration of combination type 2, =< 336 (n= 64, 60)	36 23.7%	26 17.1%
Duration of combination type 2, > 336 (n= 64, 60 )	28 18.4%	34 22.4%

11. Primary Outcome

Title	Phase I: Number of Participants Treatment Line in Which Monotherapy Has Been Adopted in Monotherapy
Description	The first biologic treatment line was defined as the first use of any biologic drug in treatment of rheumatoid arthritis, regardless its association with DMARDs and the second treatment line as the subsequent use of a different biologic drug. Participants who adopted monotherapy as =< 2 and > 2 therapy lines are reported. According to the study protocol objectives, this analysis was performed only for Monotherapy arm.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	152
Treatment line, =< 2	106 69.7%
Treatment line, > 2	46 30.3%

12. Primary Outcome

Title	Phase I: Number of Biologics Administered as Monotherapy in Monotherapy and Combination Therapy
Description	Participants who received at least one previous treatment with biologics in monotherapy and no previous monotherapy with biologics are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	152	152
No biologics	95 62.5%	125 82.2%
At least one biologics	57 37.5%	27 17.8%

13. Primary Outcome

Title	Phase I: Number of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy
Description	Participants who had prevalence with at least one previous switch, swaps, and switch/swap to other therapy are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	152	152
At least one switch	30 19.7%	40 26.3%
At least one swap	74 48.7%	56 36.8%
At least one switch/swap	81 53.3%	75 49.3%

14. Primary Outcome

Title	Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy
Description	Reasons leading to the use of biologic in monotherapy includes DMARDs intolerance, insufficient therapeutic effect, intolerance to biologic drug, low participant's compliance, concomitant pathologies, pregnancy desire, remission from combination therapy, remission from monotherapy, others and unknown. Participants with reason leading to the use of biologic in monotherapy are presented. According to the study protocol objectives, this analysis was performed only for Monotherapy arm.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	152
DMARDs intolerance	41 27%
Insufficient therapeutic effect	68 44.7%
Intolerance to biologic drug	7 4.6%
Low participant compliance	5 3.3%
Concomitant pathologies	4 2.6%
Pregnancy desire	3 2%
Remission from combination therapy	9 5.9%
Remission from monotherapy	3 2%
Others	8 5.3%
Unknown	3 2%

15. Primary Outcome

Title	Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy
Description	The probabilities of participant to retain on therapy at various time points are reported.
Time Frame	Up to 18 months

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
Day 1	99.0 65.1%
Day 33	97.1 63.9%
Day 66	96.2 63.3%
Day 168	95.2 62.6%
Day 236	94.2 62%
Day 323	93.3 61.4%
Day 375	92.3 60.7%
Day 414	91.3 60.1%
Day 423	90.4 59.5%
Day 442	89.4 58.8%
Day 459	88.5 58.2%

16. Primary Outcome

Title	Phase II: Retention Rate in Therapy, Percentage of Participants Achieving DAS 28 ESR <2.6 and <3.2 at Month 18
Description	Participants who retained the therapy were analyzed for disease activity (DAS28 ESR) at Month 18. The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease.
Time Frame	At month 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
DAS28 ESR<2.6	64.71 42.6%
DAS 28 ESR > 2.6 to =<3.2	80.39 52.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy
	Comments	The relation between retention rate and DAS28 (<2.6 vs <3.2) was assayed with the Cox regression.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1194
	Comments	The relation between retention rate and duration of disease for phase II was estimated with the Cox regression model.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	3.538
	Confidence Interval	(2-Sided) 95% 0.65 to 19.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Phase I: Median Disease Duration in Monotherapy and Combination Therapy
Description	The duration of disease is defined as the total time from the diagnosis of RA until the study entry.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with DMARDs in the 12 months prior to study entry were observed for Phase I.
Measure Participants	152	152
Median (95% Confidence Interval) [Months]	125	114

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy, Combination Therapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3895
	Comments
	Method	Regression, Cox
	Comments

18. Secondary Outcome

Title	Phase I: Percentage of Participants With Comorbidity in Monotherapy and Combination Therapy
Description	Comorbidity is the presence of previous or concomitant diseases. Percentage of participants with comorbidity is reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with DMARDs in the 12 months prior to study entry were observed for Phase I.
Measure Participants	152	152
Number [Percentage of participants]	79.61 52.4%	76.32 50.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy, Combination Therapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4900
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.211
	Confidence Interval	(2-Sided) 95% 0.703 to 2.086
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Phase I: Mean Health Assessment Questionnaire-Disability Index in Monotherapy and Combination Therapy
Description	The HAQ-DI is a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatoid arthritis. It consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity. Participants assessed their ability to do each task over the past seven days.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with DMARDs in the 12 months prior to study entry were observed for Phase I.
Measure Participants	152	152
Mean (Standard Deviation) [Scores on scale]	0.873 (0.686)	0.915 (0.667)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy, Combination Therapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6908
	Comments
	Method	t-test, 2 sided
	Comments

Method of Estimation	Estimation Parameter	Delta
	Estimated Value	-0.042
	Confidence Interval	(2-Sided) 95% -0.251 to 0.167
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Phase I: Percentage of Participants Who Started Treatment With a Biologic Drug in Monotherapy and Percentage of Participants Who Stopped a DMARDs While Taking a Biologic Drug in Combination Therapy
Description	The table below shows percentage participants who started treatment with a biologic drug in monotherapy compared with percentage of participants who stopped DMARDs while taking a biologic drug in combination.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. One participant in monotherapy group and 4 participants in combination group were not included because they had not received a previous treatment.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with DMARDs in the 12 months prior to study entry were observed for Phase I.
Measure Participants	151	148
Number (95% Confidence Interval) [Percentage of Participants]	49.01 32.2%	35.81 23.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy, Combination Therapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0210
	Comments
	Method	Pearson's chi-squared test
	Comments

21. Secondary Outcome

Title	Phase I: Number of Participants Receiving a Biologic Drug as Monotherapy at Different Treatment Lines
Description	The first biologic treatment line was defined as the first use of any biologic drug in treatment of rheumatoid arthritis, regardless its association with DMARDs, the second treatment line as the subsequent use of a different biologic drug and so on for the third, fourth, fifth and sixth treatment line. According to the study protocol objectives, this analysis was performed only for Monotherapy arm.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	152
Treatment Line 1	71 46.7%
Treatment Line 2	35 23%
Treatment Line 3	35 23%
Treatment Line 4	6 3.9%
Treatment Line 5	4 2.6%
Treatment Line 6	1 0.7%

22. Secondary Outcome

Title	Phase I: Number of Participants With at Least One Previous Treatment With Biologics Drug as a Monotherapy in Monotherapy and Combination Therapy
Description	Number of participants who received at least one previous treatment with a biologic drug as a monotherapy in both groups is reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. One participant in monotherapy group and 4 participants in combination group were not included because they had not received a previous treatment.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with DMARDs in the 12 months prior to study entry were observed for Phase I.
Measure Participants	151	148
Number [Participants]	57 37.5%	27 17.8%

23. Secondary Outcome

Title	Phase I: Percentage of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy
Description	Participants who had prevalence with at least one previous switch, swaps or switch/swap to other therapy either monotherapy or combination therapy are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with DMARDs in the 12 months prior to study entry were observed for Phase I.
Measure Participants	152	152
Switch	19.74 13%	26.32 17.3%
Swap	48.68 32%	36.84 24.2%
Switch/Swap	53.29 35.1%	49.34 32.5%

24. Secondary Outcome

Title	Phase I: Median DAS28 at Study Entry in Monotherapy and Combination Therapy
Description	The DAS28 is a combined index for measuring disease activity in RA. The index includes SJC and TJC, acute phase response, and general health status. The DAS28 scale ranges from 0 to 10 (0= no disease activity and 10= maximum disease activity) where higher scores represents higher disease. The DAS28 <2.6 indicates disease remission, >=2.6 and <3.2 indicates Low disease activity, >=3.2 and <=5.1 indicates Moderate disease activity and >5.1 indicates High disease activity. Median score for DAS28 at the study entry (Baseline) is reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available DAS28 score at Baseline are reported.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with DMARDs in the 12 months prior to study entry were observed for Phase I.
Measure Participants	121	122
Median (Full Range) [Scores on scale]	2.51	2.77

25. Secondary Outcome

Title	Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy
Description	The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment; and PtGA and PhGA assessed on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =< 2.8 indicates clinical remission, > 2.8 to 10 indicates low disease activity, > 10 to 22 indicates moderate disease activity, and > 22 indicates high disease activity. Number of participants with CDAI scores for both the groups at study entry (baseline) are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available CDAI score at Baseline are reported.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with DMARDs in the 12 months prior to study entry were observed for Phase I.
Measure Participants	74	77
Disease remission	18 11.8%	16 10.5%
Low disease activity	28 18.4%	30 19.7%
Moderate disease activity	20 13.2%	21 13.8%
High disease activity	8 5.3%	10 6.6%

26. Secondary Outcome

Title	Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy
Description	The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (assessed on 0-10 cm) VAS; 0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available SDAI score at Baseline are reported.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with DMARDs in the 12 months prior to study entry were observed for Phase I.
Measure Participants	72	69
Disease remission	19 12.5%	17 11.2%
Low disease activity	25 16.4%	26 17.1%
Moderate disease activity	22 14.5%	20 13.2%
High disease activity	6 3.9%	6 3.9%

27. Secondary Outcome

Title	Phase I: Mean Tender Joints and Swollen Joints as Disease Activity at Study Entry in Monotherapy and Combination Therapy
Description	Mean of tender and swollen joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender and swollen joints was recorded on the joint assessment as no tenderness = 0 and tenderness = 1.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants with available tender and swollen joints at Baseline are reported.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with DMARDs in the 12 months prior to study entry were observed for Phase I.
Measure Participants	138	133
Tender Joints	2.49 (3.30)	2.71 (3.75)
Swollen Joints	1.29 (2.34)	1.20 (2.45)

28. Secondary Outcome

Title	Phase I: Percentage of Participants Treated With Corticosteroids at Study Entry in Monotherapy and Combination Therapy
Description	The percentage of participants treated with corticosteroids at enrollment is reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	152	152
Number (95% Confidence Interval) [Percentage of participants]	46.05 30.3%	55.26 36.4%

29. Secondary Outcome

Title	Phase I: Mean Dose of Corticosteroids At Study Entry in Monotherapy and Combination Therapy
Description	Mean dose of corticosteroids at study entry (Baseline) is reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants who received corticosteroids were considered for this outcome measure.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	70	84
Mean (Standard Deviation) [milligrams]	4.64 (3.00)	4.71 (3.12)

30. Secondary Outcome

Title	Phase I: Mean Duration of Previous Treatment With a Biologic Drug in Monotherapy and Combination Therapy
Description	Mean duration of previous treatment with a biologic drug in monotherapy are reported.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants who received previous treatment with a biologic drug before monotherapy were considered for this outcome measure.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	46	22
Mean (Standard Deviation) [Days]	1254.7 (816.0)	1188.3 (995.0)

31. Secondary Outcome

Title	Phase I: Mean Duration of Treatment With A Biologic Drug in Combination With DMARDs Before Monotherapy
Description	Mean duration of treatment with a biologic drug in combination with DMARDs before monotherapy is reported in days.
Time Frame	At Baseline (Day of informed consent form signed)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants. Participants who received previous treatment with a biologic drug in combination with DMARDs before monotherapy were considered for this outcome measure.

Arm/Group Title	Monotherapy	Combination Therapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.	Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I.
Measure Participants	82	75
Mean (Standard Deviation) [Days]	1486.1 (988.4)	1525.9 (1132.1)

32. Secondary Outcome

Title	Phase II: Percentage of Participants Maintaining Delta DAS 28 CRP of >= 0.6 at Months 3, 6, 12, and 18
Description	Participants who maintained the change in DAS28 (Delta DAS28) CRP of >=0.6 after 3, 6, 12, and 18 months from the first infusion with tocilizumab as monotherapy are reported. The DAS28-CRP is a combined index that measured RA disease activity. It is calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). It is calculated by using the formula: DAS28 CRP= 0.56 × square root of TJC 28 + 0.28 square root of SJC 28 + 0.36 × log n at (CRP+1) + 0.014 × PtGA + 0.96. The DAS28 CRP- scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease.
Time Frame	At Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
Month 3	55.36 36.4%
Month 6	56.6 37.2%
Month 12	60.78 40%
Month 18	60 39.5%

33. Secondary Outcome

Title	Phase II: Percentage of Participants Maintaining Delta DAS28 ESR >= 0.6 at Months 3, 6, 12, and 18
Description	Participants who maintained delta DAS28 ESR of >= 0.6 after 3, 6, 12, and 18 months from the first infusion with tocilizumab as monotherapy are reported. The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); where decrease in score indicated improvement of disease.
Time Frame	At Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
Month 3	55.00 36.2%
Month 6	67.86 44.6%
Month 12	58.82 38.7%
Month 18	72.55 47.7%

34. Secondary Outcome

Title	Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18
Description	The DAS28-CRP is a combined index that measured RA disease activity. It is calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). It is calculated by using the formula: DAS28 CRP= 0.56 × square root of TJC (28 joints) + 0.28 square root of SJC (28 joints) + 0.36 × log n at (CRP+1) + 0.014 × PtGA + 0.96. The DAS28 CRP scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease. The DAS28 CRP < 2.6 indicates disease remission and >=2.6 to 3.2 indicates low disease activity.
Time Frame	At Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
DAS28 CRP < 2.6, Month 3	18.18 12%
DAS28 CRP < 2.6, Month 6	43.1 28.4%
DAS28 CRP < 2.6, Month 12	64.15 42.2%
DAS28 CRP < 2.6, Month 18	60.78 40%
DAS28 CRP < 3.2, Month 3	32.73 21.5%
DAS28 CRP < 3.2, Month 6	67.24 44.2%
DAS28 CRP < 3.2, Month 12	84.91 55.9%
DAS28 CRP < 3.2, Month 18	76.47 50.3%

35. Secondary Outcome

Title	Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18
Description	The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease. The DAS28 ESR < 2.6 indicates disease remission and >=2.6 to 3.2 indicates low disease activity.
Time Frame	At Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
DAS28 ESR < 2.6, Month 3	14.04 9.2%
DAS28 ESR < 2.6, Month 6	42.62 28%
DAS28 ESR < 2.6, Month 12	53.57 35.2%
DAS28 ESR < 2.6, Month 18	64.71 42.6%
DAS28 ESR < 3.2, Month 3	24.56 16.2%
DAS28 ESR < 3.2, Month 6	70.49 46.4%
DAS28 ESR < 3.2, Month 12	83.93 55.2%
DAS28 ESR < 3.2, Month 18	80.39 52.9%

36. Secondary Outcome

Title	Phase II: Percentage of Participants Achieving CDAI Remission (< 2.8) at Months 3, 6, 12, and 18
Description	Percentage of participants achieving CDAI remission < 2.8, after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy are reported. CDAI is the numerical sum of four outcome parameters: TJC, SJC based on a 28-joint assessment; and PtGA and PhGA assessed on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =< 2.8 indicates clinical remission, > 2.8 to 10 indicates low disease activity, > 10 to 22 indicates moderate disease activity, and > 22 indicates high disease activity.
Time Frame	At Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
Month 3	11.11 7.3%
Month 6	16.67 11%
Month 12	33.33 21.9%
Month 18	31.58 20.8%

37. Secondary Outcome

Title	Phase II: Percentage of Participant Achieving SDAI Remission (< 3.3) at Months 3, 6, 12, and 18
Description	Percentage of participant achieving SDAI remission (< 3.3), after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy is reported. The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA which (based on 0-10 cm VAS, 0 = no disease activity and 10 = worst disease activity, where higher scores represent higher disease activity), and CRP. The SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity.
Time Frame	At Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
Month 3	12.5 8.2%
Month 6	22.22 14.6%
Month 12	50.00 32.9%
Month 18	36.36 23.9%

38. Secondary Outcome

Title	Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18
Description	The mean change from Baseline (day of the first infusion with tocilizumab as monotherapy) in the TJC And SJC after 3, 6, 12 and 18 months is reported. The TJC and SJC were determined for 28 joint counts. The scores ranged from 0 (no disease activity) to 28 (higher/worsen disease activity), where higher scores represents higher disease activity.
Time Frame	From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	80
TJC, Month 3 (n= 78)	-2.74 (6.87)
TJC, Month 6 (n= 80)	-4.13 (5.51)
TJC, Month 12 (n= 72)	-4.33 (6.14)
TJC, Month 18 (n= 69)	-4.30 (5.89)
SJC, Month 3 (n= 78)	-1.65 (3.98)
SJC, Month 6 (n= 80)	-2.39 (3.47)
SJC, Month 12 (n= 72)	-2.21 (3.76)
SJC, Month 18 (n= 69)	-2.46 (3.75)

39. Secondary Outcome

Title	Phase II: Mean Change From Baseline in Dose of Corticosteroids at Months 3, 6, 12, and 18
Description	Mean Change From Baseline (day of the first infusion with tocilizumab as monotherapy) in the dose of corticosteroids after 3, 6, 12 and 18 months from Baseline is reported.
Time Frame	From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	60
Month 3 (n= 60)	-0.85 (4.18)
Month 6 (n= 54)	-1.24 (2.28)
Month 12 (n= 41)	-1.71 (2.76)
Month 18 (n= 38)	-1.08 (2.12)

40. Secondary Outcome

Title	Phase II: Percentage of Participants With Delta HAQ >= 0.21 at Months 3, 6, 12, and 18
Description	Percentage of participants with change in HAQ (Delta HAQ) of >= 0.21 after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy are reported. The HAQ consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity.
Time Frame	At Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
Month 3	8.51 5.6%
Month 6	10.00 6.6%
Month 12	13.89 9.1%
Month 18	8.11 5.3%

41. Secondary Outcome

Title	Phase II: Mean VAS Fatigue Score Overtime
Description	The VAS fatigue score ranging from 0 (symptom-free and no arthritis symptoms) to 100 (worsening in symptoms and arthritis disease activity). Higher score indicate worsening.
Time Frame	At Baseline (Day of first administration of TCZ as a monotherapy) and Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	24
Baseline (n= 19)	54.95 (25.49)
Month 3 (n= 24)	40.58 (20.67)
Month 6 (n= 24)	30.42 (21.20)
Month 12 (n= 17)	33.82 (23.72)
Month 18 (n= 23)	23.35 (25.01)

42. Secondary Outcome

Title	Phase II: Number of Participants With Any Adverse Events, Any Serious Adverse Events, Adverse Events of Special Interest, and Tubercular Events
Description	An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AE. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death is life threatening, requires hospitalization or prolongation of hospitalization, or results in disability/incapacity, or congenital anomaly/birth defect. The AE were captured only for Phase II.
Time Frame	Up to 18 months

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
Any AE	56 36.8%
Any SAE	5 3.3%
AE/SAE of special interest	10 6.6%
Tubercular AE/SAE	0 0%

43. Secondary Outcome

Title	Phase II: Number of Participants With Retention in Therapy Without Interruption Due to Side Effects
Description	Number of participants who retained in therapy without interruption due to side effects is reported.
Time Frame	Up to 18 months

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
Number [Participants]	103 67.8%

44. Secondary Outcome

Title	Phase II: Number of Side Effects That Had Not Induced Discontinuation of Treatment
Description	Number of side effects (AEs) that had not induced discontinuation of treatment is reported. The AEs were captured only for Phase II.
Time Frame	Up to 18 months

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
Number [AEs]	19

45. Secondary Outcome

Title	Phase II: Number of Side Effects That Induced Transient Interruption of Treatment
Description	Number of side effects (AEs) that induced transient interruption of treatment is reported. The AEs were captured only for Phase II.
Time Frame	Up to 18 months

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	104
Number [AEs]	15

46. Secondary Outcome

Title	Phase II: Mean Change From Baseline in Hemoglobin Levels Over Time
Description	The mean change in hemoglobin concentration was calculated by subtracting the baseline hemoglobin concentration from the monthly hemoglobin concentration is reported.
Time Frame	From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	84
Month 3 (n= 83)	0.41 (0.84)
Month 6 (n= 84)	0.34 (0.91)
Month 12 (n= 80)	0.44 (1.01)
Month 18 (n= 76)	0.49 (1.16)

47. Secondary Outcome

Title	Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time
Description	Mean Change from Baseline in hematocrit, neutrophils, eosinophils, basophils, lymphocytes, monocytes are reported.
Time Frame	From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	64
Hematocrit, Month 3 (n= 60)	5.73 (36.25)
Hematocrit, Month 6 (n= 57)	-0.11 (7.12)
Hematocrit, Month 12 (n= 57)	0.32 (7.26)
Hematocrit, Month 18 (n= 53)	-0.35 (8.35)
Neutrophils, Month 3 (n= 61)	-7.82 (11.96)
Neutrophils, Month 6 (n= 64)	-7.69 (11.35)
Neutrophils, Month 12 (n= 57)	-7.16 (11.99)
Neutrophils, Month 18 (n= 55)	-6.69 (13.32)
Eosinophils, Month 3 (n= 58)	1.21 (2.54)
Eosinophils, Month 6 (n= 59)	1.25 (2.11)
Eosinophils, Month 12 (n= 52)	1.30 (2.49)
Eosinophils, Month 18 (n= 51)	1.31 (2.16)
Basophils, Month 3 (n= 58)	0.14 (0.67)
Basophils, Month 6 (n= 59)	0.26 (0.63)
Basophils, Month 12 (n= 52)	0.19 (0.47)
Basophils, Month 18 (n= 51)	0.18 (0.41)
Lymphocytes, Month 3 (n= 60)	5.58 (9.05)
Lymphocytes, Month 6 (n= 64)	5.60 (9.50)
Lymphocytes, Month 12 (n= 57)	4.98 (9.67)
Lymphocytes, Month 18 (n= 55)	4.55 (11.45)
Monocytes, Month 3 (n= 58)	0.61 (2.87)
Monocytes, Month 6 (n= 59)	1.13 (2.75)
Monocytes, Month 12 (n= 52)	0.46 (2.38)
Monocytes, Month 18 (n= 51)	0.59 (2.74)

48. Secondary Outcome

Title	Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time
Description	Mean change from baseline in red blood cells (RBC), white blood cells (WBC) and platelets are reported.
Time Frame	From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	84
RBC, Month 3 (n= 71)	0.07 (0.32)
RBC, Month 6 (n= 70)	-0.01 (0.30)
RBC, Month 12 (n= 69)	0.04 (0.32)
RBC, Month 18 (n= 63)	0.05 (0.29)
WBC, Month 3 (n= 83)	-1.14 (2.01)
WBC, Month 6 (n= 84)	-1.30 (2.27)
WBC, Month 12 (n= 81)	-1.30 (2.09)
WBC, Month 18 (n= 75)	-1.48 (2.15)
Platelets, Month 3 (n= 78)	-52.38 (71.21)
Platelets, Month 6 (n= 75)	-62.12 (72.58)
Platelets, Month 12 (n= 73)	-54.42 (73.40)
Platelets, Month 18 (n= 72)	-57.88 (76.15)

49. Secondary Outcome

Title	Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time
Description	Mean change from baseline in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), total bilirubin, direct bilirubin, glucose, creatinine, blood urea nitrogen (BUN) levels are reported.
Time Frame	From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	64
Total Cholesterol, Month 3 (n= 27)	10.04 (42.31)
Total Cholesterol, Month 6 (n= 28)	12.61 (49.76)
Total Cholesterol, Month 12 (n= 31)	4.81 (41.59)
Total Cholesterol, Month 18 (n= 28)	5.57 (49.00)
LDL Cholesterol, Month 3 (n= 14)	-3.63 (24.89)
LDL Cholesterol, Month 6 (n= 14)	13.93 (38.99)
LDL Cholesterol, Month 12 (n= 16)	-2.59 (37.10)
LDL Cholesterol, Month 18 (n= 14)	3.53 (38.31)
HDL Cholesterol, Month 3 (n= 19)	4.16 (6.34)
HDL Cholesterol, Month 6 (n= 18)	0.67 (11.42)
HDL Cholesterol, Month 12 (n= 19)	-1.74 (12.61)
HDL Cholesterol, Month 18 (n= 18)	-1.67 (15.46)
TG, Month 3 (n= 23)	-7.91 (45.29)
TG, Month 6 (n= 27)	-2.78 (50.39)
TG, Month 12 (n= 26)	2.85 (53.05)
TG, Month 18 (n= 27)	12.93 (71.09)
Total Bilirubin, Month 3 (n= 5)	0.28 (0.29)
Total Bilirubin, Month 6 (n= 9)	0.18 (0.45)
Total Bilirubin, Month 12 (n= 9)	0.04 (0.28)
Total Bilirubin, Month 18 (n= 7)	0.36 (0.74)
Direct Bilirubin, Month 3 (n= 5)	0.08 (0.17)
Direct Bilirubin, Month 6 (n= 9)	0.06 (0.28)
Direct Bilirubin, Month 12 (n= 9)	0.03 (0.28)
Direct Bilirubin, Month 18 (n= 7)	0.13 (0.21)
Glucose, Month 3 (n= 16)	2.50 (9.00)
Glucose, Month 6 (n= 21)	4.13 (29.90)
Glucose, Month 12 (n= 24)	8.24 (27.36)
Glucose, Month 18 (n= 20)	-2.10 (26.15)
Creatinine, Month 3 (n= 60)	-0.02 (0.20)
Creatinine, Month 6 (n= 64)	-0.21 (1.29)
Creatinine, Month 12 (n= 60)	-0.33 (1.60)
Creatinine, Month 18 (n= 53)	-0.38 (1.70)
BUN, Month 3 (n= 22)	1.31 (8.87)
BUN, Month 6 (n= 25)	1.14 (8.80)
BUN, Month 12 (n= 24)	-0.18 (8.31)
BUN, Month 18 (n= 22)	0.06 (8.91)

50. Secondary Outcome

Title	Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time
Description	Mean change from baseline in aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase levels are reported.
Time Frame	From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	76
AST, Month 3 (n= 74)	0.75 (9.35)
AST, Month 6 (n= 74)	0.87 (9.39)
AST, Month 12 (n= 74)	0.78 (8.47)
AST, Month 18 (n= 68)	1.53 (13.40)
ALT, Month 3 (n= 74)	3.08 (20.65)
ALT, Month 6 (n= 76)	0.60 (20.49)
ALT, Month 12 (n= 76)	0.08 (16.15)
ALT, Month 18 (n= 68)	0.22 (18.27)
GGT, Month 3 (n= 25)	-0.84 (20.45)
GGT, Month 6 (n= 32)	-6.19 (24.68)
GGT, Month 12 (n= 30)	-4.60 (21.50)
GGT, Month 18 (n= 25)	-7.48 (26.50)
Alkaline phosphatase, Month 3 (n= 20)	-15.10 (38.22)
Alkaline phosphatase, Month 6 (n= 21)	-21.86 (38.02)
Alkaline phosphatase, Month 12 (n= 24)	-18.17 (44.29)
Alkaline phosphatase, Month 18 (n= 15)	-21.60 (53.45)

51. Secondary Outcome

Title	Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time
Description	Serum electrophoresis parameters includes albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, gamma globulin was reported. Mean change from Baseline values are reported at each time points.
Time Frame	From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description
Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
Measure Participants	26
Albumin, Month 3 (n= 25)	3.92 (4.23)
Albumin, Month 6 (n= 25)	5.23 (3.29)
Albumin, Month 12 (n= 24)	5.35 (5.14)
Albumin, Month 18 (n= 19)	5.95 (4.45)
Alpha-1 globulin, Month 3 (n= 26)	-0.85 (0.94)
Alpha-1 globulin, Month 6 (n= 25)	-1.09 (0.91)
Alpha-1 globulin, Month 12 (n= 25)	-1.00 (1.10)
Alpha-1 globulin, Month 18 (n= 19)	-1.11 (1.03)
Alpha-2 globulin, Month 3 (n= 25)	-1.74 (2.12)
Alpha-2 globulin, Month 6 (n= 25)	-1.68 (2.30)
Alpha-2 globulin, Month 12 (n= 24)	-1.91 (1.95)
Alpha-2 globulin, Month 18 (n= 19)	-2.34 (1.89)
Beta globulin, Month 3 (n= 25)	-0.94 (1.36)
Beta globulin, Month 6 (n= 24)	-1.19 (1.43)
Beta globulin, Month 12 (n= 24)	-0.91 (1.41)
Beta globulin, Month 18 (n= 19)	-1.07 (1.18)
Gamma globulin, Month 3 (n= 25)	-0.51 (1.96)
Gamma globulin, Month 6 (n= 26)	-1.75 (3.46)
Gamma globulin, Month 12 (n= 24)	-1.51 (2.44)
Gamma globulin, Month 18 (n= 19)	-1.52 (2.62)

Adverse Events

	Monotherapy
Time Frame	Up to 18 months
Adverse Event Reporting Description	AEs are collected for participants who were enrolled in Phase I and received TCZ as a monotherapy for 18 months from the first infusion of TCZ in Phase II. AEs were not collected for participants who received Combination therapy.

Arm/Group Title	Monotherapy
Arm/Group Description	Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice.
All Cause Mortality
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Monotherapy
	Affected / at Risk (%)	# Events
Total	5/104 (4.8%)
Cardiac disorders
Acute coronary syndrome	1/104 (1%)
Infections and infestations
Otitis externa	1/104 (1%)
Renal and urinary disorders
Renal colic	1/104 (1%)
Respiratory, thoracic and mediastinal disorders
Bronchopneumonia	1/104 (1%)
Interstitial lung disease	1/104 (1%)
Other (Not Including Serious) Adverse Events
	Monotherapy
	Affected / at Risk (%)	# Events
Total	54/104 (51.9%)
Blood and lymphatic system disorders
Leukopenia	1/104 (1%)
Neutropenia	8/104 (7.7%)
Polycythaemia	1/104 (1%)
Thrombocytopenia	2/104 (1.9%)
Cardiac disorders
Atrial fibrillation	1/104 (1%)
Cardiovascular disorder	1/104 (1%)
Ear and labyrinth disorders
Otitis media	1/104 (1%)
Eye disorders
Keratitis	1/104 (1%)
Conjunctivitis	3/104 (2.9%)
Gastrointestinal disorders
Tooth abscess	1/104 (1%)
Diarrhoea	1/104 (1%)
Abdominal pain upper	1/104 (1%)
Pharyngitis	1/104 (1%)
Gastroenteritis	1/104 (1%)
Gastroenteritis viral	2/104 (1.9%)
Oral herpes	1/104 (1%)
Gastrointestinal infection	1/104 (1%)
Vomiting	1/104 (1%)
Procedural vomiting	1/104 (1%)
General disorders
Influenza like illness	1/104 (1%)
Hepatobiliary disorders
Hepatic function abnormal	1/104 (1%)
Immune system disorders
Hypogammaglobulinaemia	1/104 (1%)
Anaphylactic reaction	1/104 (1%)
Infections and infestations
Gengival abscess	1/104 (1%)
Bacteriuria	1/104 (1%)
Bronchitis	5/104 (4.8%)
Genital candidasis	1/104 (1%)
Vulvovaginal candidasis	1/104 (1%)
Keratitis viral	1/104 (1%)
Cystitis	2/104 (1.9%)
Gastroenteritis viral	1/104 (1%)
Herpes zoster	1/104 (1%)
Upper respiratory tract infection bacterial	1/104 (1%)
Urinary tract infection bacterial	1/104 (1%)
Helicobacter infection	1/104 (1%)
Upper respiratory tract infection	1/104 (1%)
Urinary tract infection	3/104 (2.9%)
Wound infection	1/104 (1%)
Influenza	2/104 (1.9%)
Nasopharyngitis	1/104 (1%)
Injury, poisoning and procedural complications
Humerus fracture	1/104 (1%)
Wound infection	1/104 (1%)
Investigations
Neutrophil count decreased	1/104 (1%)
Ultrasound kidney abnormal	1/104 (1%)
Gamma-glutamyltransferase increased	1/104 (1%)
Hysteroscopy	1/104 (1%)
Transaminases increased	1/104 (1%)
Metabolism and nutrition disorders
Hypercholesterolaemia	2/104 (1.9%)
Osteoporosis	1/104 (1%)
Musculoskeletal and connective tissue disorders
Ligament sprain	1/104 (1%)
Neck pain	1/104 (1%)
Back pain	1/104 (1%)
Lumbar vertebral fracture	1/104 (1%)
Myalgia	1/104 (1%)
Nervous system disorders
Headache	1/104 (1%)
Memory impairment	1/104 (1%)
Congenital neurological disorder	1/104 (1%)
Hypoaesthesia	1/104 (1%)
Renal and urinary disorders
Cystitis bacterial	1/104 (1%)
Renal colic	1/104 (1%)
Reproductive system and breast disorders
Breast mass	1/104 (1%)
Metrorrhagia	1/104 (1%)
Respiratory, thoracic and mediastinal disorders
Bronchitis	1/104 (1%)
Musculoskeletal chest pain	1/104 (1%)
Pharyngitis	3/104 (2.9%)
Respiratory tract infection	1/104 (1%)
Pharyngeal inflammation	1/104 (1%)
Influenza	1/104 (1%)
Pneumonitis	1/104 (1%)
Rinitis	2/104 (1.9%)
Tonsillitis	1/104 (1%)
Tonsillitis streptococcal	1/104 (1%)
Cough	3/104 (2.9%)
Productive cough	1/104 (1%)
Skin and subcutaneous tissue disorders
Alopecia	2/104 (1.9%)
Dry skin	1/104 (1%)
Dermatitis	1/104 (1%)
Eczema	1/104 (1%)
Herpes zoster	1/104 (1%)
Pruritus generalised	1/104 (1%)
Surgical and medical procedures
Anal fistula excision	1/104 (1%)
Cardiac pacemaker insertion	1/104 (1%)
Dental operation	1/104 (1%)
Foot operation	1/104 (1%)
Uterine polypectomy	1/104 (1%)
Synovectomy	1/104 (1%)
Vascular disorders
Hypertensive crisis	3/104 (2.9%)
Hypertension	2/104 (1.9%)
Withdrawal hypertension	1/104 (1%)
Essential hypertension	1/104 (1%)
Syncope	1/104 (1%)

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	Roche Trial Information Hotline
Organization	F. Hoffmann-La Roche AG
Phone	+41 616878333
Email	global.trial_information@roche.com

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01791205

Other Study ID Numbers:

ML28552

First Posted:

Feb 13, 2013

Last Update Posted:

Jan 10, 2017

Last Verified:

Nov 1, 2016