A Study to Evaluate Efficacy of Tocilizumab Administered as Monotherapy or in Combination With Methotrexate and/or Other Disease Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis (RA) Participants

A National, Open-Label, Single-Arm, Phase IIIb Study to Evaluate the Efficacy of Weekly Tocilizumab Subcutaneous, Administered as Monotherapy or in Combination With Methotrexate and/or Other DMARDs in Rheumatoid Arthritis (RA) Patients

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01941940

Enrollment

227

Registered

2013-09-13

Start date

2013-09-05

Completion date

2016-07-05

Last updated

2017-07-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Brief summary

This open-label, single arm, Phase 3b study will evaluate the efficacy of tocilizumab (RoActemra), administered as monotherapy or in combination with methotrexate and/or other DMARDs, in participants with moderate to severe active RA.

Interventions

DRUGTocilizumab

Tocilizumab at a fixed dose of 162 mg as SC injection will be administered once every week.

DRUGDMARDs

Non-biologic DMARDs according to standard of care, at a stable dose that was initiated at least 4 weeks prior to baseline.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria * Moderate to severe RA (CDAI at least \[\>/=\] 10 and DAS28 \>/=3.2) at screening * Tumor necrosis factor inhibitors-inadequate responder (TNF-IR), methotrexate-inadequate responder (MTX-IR), and/or DMARDs-inadequate responder (DMARDs-IR) * Oral corticosteroids (less than or equal to \[\</=\] 10 mg per day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for \>/=4 weeks prior to baseline * Permitted non-biologic DMARDs are allowed if at a stable dose for \>/=4 weeks prior to baseline * Receiving treatment on an outpatient basis, not including tocilizumab * Females of childbearing potential and males with female partners of childbearing potential must agree to use a reliable means of contraception for at least 3 months following the last dose of tocilizumab

Exclusion criteria

* Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 12 months following baseline * Rheumatic autoimmune disease other than RA; secondary Sjögren's syndrome with RA is permitted * Functional Class IV as defined by the ACR Classification of Functional Status in RA * Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16 * Prior history of or current inflammatory joint disease other than RA * Exposure to tocilizumab (either intravenous \[IV\] or SC) at any time prior to baseline * Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening * Previous treatment with any cell-depleting therapies * Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline * History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies * Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease * Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections * Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening * Active tuberculosis (TB) requiring treatment within the previous 3 years * Positive for hepatitis B surface antigen or hepatitis C antibody * Primary or secondary immunodeficiency (history of or currently active) * Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (except for basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years * Pregnant or breast feeding women * Neuropathies or other conditions that might interfere with pain evaluation

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24	Baseline, Week 24	The CDAI is a numerical sum of 4 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient's global assessment of disease activity (PtGDA) and physician global assessment of disease activity (PGDA) assessed on 0-10 centimeters (cm) visual analogue scale (VAS). Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score less than or equal to (\</=) 2.8 indicates disease remission, greater than (\>) 2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 20	Baseline, Week 20	The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 16	Baseline, Week 16	The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 12	Baseline, Week 12	The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 8	Baseline, Week 8	The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 4	Baseline, Week 4	The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 2	Baseline, Week 2	The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.

Secondary

Measure	Time frame	Description
Association Between Disease Activity Parameters: DAS28-ESR and CDAI, Assessed Using Correlation Coefficient	Weeks 2, 24, 52	DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. Higher scores indicate greater affectation due to disease activity. The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. Higher scores represent greater affectation due to disease activity. Correlation coefficient for relationship between DAS28-ESR and CDAI at different time points is reported. Correlation coefficient value range= -1 to 1. Higher positive value indicates greater positive relationship and higher negative value indicates greater negative relationship.
Association Between Disease Activity Parameters: DAS28-ESR and SDAI, Assessed Using Correlation Coefficient	Weeks 2, 24, 52	DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. Higher scores indicate greater affectation due to disease activity. SDAI is a numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. Higher scores indicate greater affectation due to disease activity. Correlation coefficient for relationship between DAS28-ESR and SDAI at different time points is reported. Correlation coefficient value range= -1 to 1. Higher positive value indicates greater positive relationship and higher negative value indicates greater negative relationship.
Association Between Disease Activity Parameters: CDAI and SDAI, Assessed Using Correlation Coefficient	Weeks 2, 24, 52	The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. Higher scores represent greater affectation due to disease activity. SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. Higher scores indicate greater affectation due to disease activity. Correlation coefficient for relationship between CDAI and SDAI at different time points is reported. Correlation coefficient value range= -1 to 1. Higher positive value indicates greater positive relationship and higher negative value indicates greater negative relationship.
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Weeks 2, 24, 52	DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. The ACR 20, 50, and 70 responses: \>/=20%, 50%, and 70% improvement in TJC and SJC, and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit. Regression coefficients for relationship between DAS28-ESR and ACR responses (ACR20, ACR50, and ACR70) at different time points are reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Weeks 2, 24, 52	DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. EULAR response criteria (based on DAS28 score): Good responders (change from baseline \>1.2 with DAS28 \</=3.2); Moderate responders (change from baseline \>1.2 with DAS28 \>3.2 to \</=5.1 or change from baseline \>0.6 to \</=1.2 with DAS28 \</=5.1); Non-responders (change from baseline \</=0.6 or change from baseline \>0.6 and \</=1.2 with DAS28 \>5.1). Regression coefficient for relationship between DAS28-ESR and EULAR Good response at different time points is reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.
Missed Working Days Assessed Using Short Form-Health and Labor Questionnaire (SF-HLQ) Score at Weeks 24 and 52	Weeks 24 and 52	The SF-HLQ assessed productivity losses related to health problems in individuals with paid or unpaid work and consisted of three modules (absenteeism from paid work, production losses without absenteeism from paid work and hindrance in the performance of paid and unpaid work). Any missed working days or number of worked days with reduced efficiency during the last month were reported.
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Weeks 2, 24, 52	The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. The ACR 20, 50, and 70 responses: \>/=20%, 50%, and 70% improvement in TJC and SJC, and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit. Regression coefficients for relationship between CDAI and ACR responses (ACR20, ACR50, and ACR70) at different time points are reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Weeks 2, 24, 52	The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. EULAR response criteria (based on DAS28 score): Good responders (change from baseline \>1.2 with DAS28 \</=3.2); Moderate responders (change from baseline \>1.2 with DAS28 \>3.2 to \</=5.1 or change from baseline \>0.6 to \</=1.2 with DAS28 \</=5.1); Non-responders (change from baseline \</=0.6 or change from baseline \>0.6 and \</=1.2 with DAS28 \>5.1). Regression coefficient for relationship between CDAI and EULAR Good response at different time points is reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Weeks 2, 24, 52	SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. The ACR 20, 50, and 70 responses: \>/=20%, 50%, and 70% improvement in TJC and SJC, and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit. Regression coefficients for relationship between SDAI and ACR responses (ACR20, ACR50, and ACR70) at different time points are reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Weeks 2, 24, 52	The SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. EULAR response criteria (based on DAS28 score): Good responders (change from baseline \>1.2 with DAS28 \</=3.2); Moderate responders (change from baseline \>1.2 with DAS28 \>3.2 to \</=5.1 or change from baseline \>0.6 to \</=1.2 with DAS28 \</=5.1); Non-responders (change from baseline \</=0.6 or change from baseline \>0.6 and \</=1.2 with DAS28 \>5.1). Regression coefficient for relationship between SDAI and EULAR Good response at different time points is reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.
Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Baseline up to Week 52	Percentage of DMARDs dose reduction and/or discontinuation (Red/Dis) events is reported by different reasons.
Number of Participants Achieving Clinical Remission According to CDAI up to Week 52	Baseline up to Week 52 (Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 38, and 52)	The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 during any two consecutive visits, not including the baseline visit indicates disease remission.
Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52	Baseline, Weeks 2, 24, and 52	Participants answered the following question: Considering all the ways your arthritis affects you, how are you feeling today. Participants responded by using a 0 - 100 millimeter (mm) VAS, where 0 mm = very well and 100 mm = very poorly.
Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52	Baseline, Weeks 2, 24, and 52	The physician assessed participant's current disease activity on a 0-100 mm VAS, where 0 mm = no disease activity and 100 mm = maximum disease activity.
Participant Pain VAS Score at Weeks 2, 24, and 52	Weeks 2, 24, and 52	Participants assessed their pain using a 0-100 mm VAS. Intensity of pain range (over past week): 0 mm = no pain to 100 mm = worst possible pain.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52	Baseline, Weeks 2, 24, and 52	HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52	Baseline, Weeks 2, 24, and 52	FACIT total score is sum of Functional Assessment of Cancer Therapy-General (FACT-G) score and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; additional concerns) score. FACT-G is a core questionnaire that evaluates quality of life (QoL) in cancer population. FACT-G consists of 27 questions grouped in 4 domains of general health-related QoL: physical well-being, social/family well-being, emotional well-being, and functional well-being; each item ranges from 0 (not at all) to 4 (very much). FACT-G score ranges between 0-108. FACIT-F is a 13-item questionnaire that evaluates self-reported fatigue and its impact upon daily activities. Each item ranges from 0 (Not at all) to 4 (Very much). The sum of all responses result in the FACIT total score with a total possible range of 0 (better score) to 160 (worse score). Negative change from baseline represents a better QoL.
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) at Weeks 24 and 52	Baseline, Weeks 24 and 52	PSQI is a questionnaire with 18 questions to assess sleep quality. The 18 questions are distributed to 7 elements (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction). A participant indicates how frequently each item was experienced on a scale from 0 to 3. The global score is the sum score of all 7 elements and ranges from 0-21 with higher values indicating worse sleep quality. A score of \>/=5 indicates poor sleepers.
Treatment Compliance, as Assessed Using Participant Diary Cards and Return Records	Weeks 24 and 52	Treatment Compliance was calculated as (total actual doses taken for the period) / (total planned or prescribed dose for the period) x 100.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) of Special Interest	Baseline up to 95 weeks	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are AEs occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state. Following AEs were considered as AEs of special interest: anaphylactic reaction, hypersensitivity, stress cardiomyopathy, Gilbert's syndrome, gastrointestinal perforation, injection site erythema, injection site hypersensitivity, injection site irritation, injection site pruritus, arthritis bacterial, cellulitis, klebsiella infection, oral candidiasis, pneumonia, skin infection, vulvovaginal candidiasis, alanine aminotransferase increased, hepatic enzyme increased, brain neoplasm malignant, and urticaria.
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab	Baseline, Weeks 12, 24, 38, 52, at 8 weeks after last dose (up to Week 60), at early withdrawal (up to Week 52), at Follow-up Visits 1 (Week 64), 2 (Week 76), and 3 (Week 88)	Percentage of participants with positive results for ATA against tocilizumab at different time points is reported.
Mean Tocilizumab Concentration	Baseline, Weeks 12, 24, 38, 52, at early withdrawal (up to Week 52), at Follow-up Visit 2 (Week 76)	—
Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration	Baseline, Weeks 12, 24, 38, 52, at early withdrawal (up to Week 52), at Follow-up Visit 2 (Week 76)	—
Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Baseline up to Week 52	Percentage of Non-DMARDs dose reduction and/or discontinuation (Red/Dis) events is reported by different reasons.
Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52	Baseline, Weeks 2, 24, and 52	DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hour) and PtGDA assessed on 0-10 cm VAS. Higher scores indicate greater affectation due to disease activity. DAS28-ESR total score= 0-9.4. DAS28-ESR \</=3.2 indicates low disease activity, DAS28-ESR \>3.2 to 5.1 indicates moderate to high disease activity, and DAS28-ESR \</=3.2 indicates remission.
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52	Baseline, Weeks 2, 24, and 52	SDAI is a numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and C-reactive protein (CRP) in milligrams per deciliter (mg/dL). Higher scores indicate greater affectation due to disease activity. SDAI total score = 0-86. 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.
Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	Weeks 2, 24, and 52	The ACR 20, 50, and 70 responses: greater than or equal to (\>/=) 20 percent (%), 50%, and 70% improvement in TJC and SJC (28 assessed joints), and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP or ESR at each visit.
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	Baseline, Weeks 2, 24, and 52	The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 \</=3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to \</=5.1 or change from baseline \>0.6 to \</=1.2 with DAS28 \</=5.1; non-responders: change from baseline \</=0.6 or change from baseline \>0.6 and \</=1.2 with DAS28 \>5.1.
Change From Baseline in Total TJC at Weeks 2, 24, and 52	Baseline, Weeks 2, 24, and 52	TJC was defined as the total number of painful joints based on 68-joint assessment (TJC-68) and 28-joint assessment (TJC-28).
Change From Baseline in Total SJC at Weeks 2, 24, and 52	Baseline, Weeks 2, 24, and 52	SJC was defined as the total number of swollen joints based on 66-joint assessment (SJC-66) and 28-joint assessment (SJC-28).

Countries

Italy

Participant flow

Pre-assignment details

Out of a total of 288 participants screened, 60 participants were excluded due to screening failure and 1 participant did not receive study treatment based on investigator's decision. Thus, total 227 participants were included in the study.

Participants by arm

Arm	Count
Tocilizumab Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).	227
Total	227

Arm

Count

Tocilizumab

Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).

227

Total

227

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	11
Overall Study	Death	1
Overall Study	Lost to Follow-up	2
Overall Study	Other	1
Overall Study	Physician Decision	2
Overall Study	Withdrawal by Subject	15

Baseline characteristics

Characteristic	Tocilizumab
Age, Continuous	54.7 years STANDARD_DEVIATION 12.12
Sex: Female, Male Female	197 Participants
Sex: Female, Male Male	30 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	36 / 227
serious Total, serious adverse events	17 / 227

Outcome results

Primary

Change From Baseline in CDAI at Week 12

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.

Time frame: Baseline, Week 12

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in CDAI at Week 12	-19.1 units on a scale	Standard Deviation 12.46

Primary

Change From Baseline in CDAI at Week 16

Time frame: Baseline, Week 16

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in CDAI at Week 16	-20.2 units on a scale	Standard Deviation 12.53

Primary

Change From Baseline in CDAI at Week 2

Time frame: Baseline, Week 2

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in CDAI at Week 2	-9.1 units on a scale	Standard Deviation 9.71

Comparison: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Primary

Change From Baseline in CDAI at Week 20

Time frame: Baseline, Week 20

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in CDAI at Week 20	-21.3 units on a scale	Standard Deviation 12.87

Primary

Change From Baseline in CDAI at Week 4

Time frame: Baseline, Week 4

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in CDAI at Week 4	-14.0 units on a scale	Standard Deviation 11.57

Primary

Change From Baseline in CDAI at Week 8

Time frame: Baseline, Week 8

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in CDAI at Week 8	-17.7 units on a scale	Standard Deviation 12.07

Primary

Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24

The CDAI is a numerical sum of 4 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient's global assessment of disease activity (PtGDA) and physician global assessment of disease activity (PGDA) assessed on 0-10 centimeters (cm) visual analogue scale (VAS). Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score less than or equal to (\</=) 2.8 indicates disease remission, greater than (\>) 2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.

Time frame: Baseline, Week 24

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24	-21.6 units on a scale	Standard Deviation 13.25

Comparison: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Secondary

Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. EULAR response criteria (based on DAS28 score): Good responders (change from baseline \>1.2 with DAS28 \</=3.2); Moderate responders (change from baseline \>1.2 with DAS28 \>3.2 to \</=5.1 or change from baseline \>0.6 to \</=1.2 with DAS28 \</=5.1); Non-responders (change from baseline \</=0.6 or change from baseline \>0.6 and \</=1.2 with DAS28 \>5.1). Regression coefficient for relationship between CDAI and EULAR Good response at different time points is reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Time frame: Weeks 2, 24, 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Week 2: CDAI and EULAR (n=220)	-10.97686 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Week 24: CDAI and EULAR (n=186)	-7.03184 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Week 52: CDAI and EULAR (n=32)	-9.46563 regression coefficient

Comparison: Analysis for association between CDAI and EULAR at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and EULAR at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and EULAR at Week 52p-value: <0.0001ANOVA

Secondary

Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. The ACR 20, 50, and 70 responses: \>/=20%, 50%, and 70% improvement in TJC and SJC, and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit. Regression coefficients for relationship between CDAI and ACR responses (ACR20, ACR50, and ACR70) at different time points are reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Time frame: Weeks 2, 24, 52

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 2: CDAI and ACR20 (n=220)	-9.65473 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 2: CDAI and ACR50 (n=220)	-10.67389 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 2: CDAI and ACR70 (n=220)	-13.38810 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 24: CDAI and ACR20 (n=186)	-13.18433 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 24: CDAI and ACR50 (n=186)	-11.95933 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 24: CDAI and ACR70 (n=186)	-11.18299 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 52: CDAI and ACR20 (n=32)	-18.94643 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 52: CDAI and ACR50 (n=32)	-18.94643 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 52: CDAI and ACR70 (n=32)	-18.94643 regression coefficient

Comparison: Analysis for association between CDAI and ACR20 at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and ACR50 at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and ACR70 at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and ACR20 at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and ACR50 at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and ACR70 at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and ACR20 at Week 52p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and ACR50 at Week 52p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and ACR70 at Week 52p-value: <0.0001ANOVA

Secondary

Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient

DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. EULAR response criteria (based on DAS28 score): Good responders (change from baseline \>1.2 with DAS28 \</=3.2); Moderate responders (change from baseline \>1.2 with DAS28 \>3.2 to \</=5.1 or change from baseline \>0.6 to \</=1.2 with DAS28 \</=5.1); Non-responders (change from baseline \</=0.6 or change from baseline \>0.6 and \</=1.2 with DAS28 \>5.1). Regression coefficient for relationship between DAS28-ESR and EULAR Good response at different time points is reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Time frame: Weeks 2, 24, 52

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Week 2: DAS28-ESR and EULAR (n=213)	-1.62883 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Week 24: DAS28-ESR and EULAR (n=182)	-1.36226 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Week 52: DAS28-ESR and EULAR (n=32)	-1.47781 regression coefficient

Comparison: Analysis for association between DAS28-ESR and EULAR at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and EULAR at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and EULAR at Week 52p-value: <0.0001ANOVA

Secondary

Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient

DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. The ACR 20, 50, and 70 responses: \>/=20%, 50%, and 70% improvement in TJC and SJC, and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit. Regression coefficients for relationship between DAS28-ESR and ACR responses (ACR20, ACR50, and ACR70) at different time points are reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Time frame: Weeks 2, 24, 52

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 2: DAS28-ESR and ACR70 (n=213)	-1.50400 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 2: DAS28-ESR and ACR20 (n=213)	-1.02676 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 2: DAS28-ESR and ACR50 (n=213)	-1.31737 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 24: DAS28-ESR and ACR20 (n=182)	-1.71191 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 24: DAS28-ESR and ACR50 (n=182)	-1.54281 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 24: DAS28-ESR and ACR70 (n=182)	-1.43977 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 52: DAS28-ESR and ACR20 (n=32)	-2.05036 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 52: DAS28-ESR and ACR50 (n=32)	-2.05036 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 52: DAS28-ESR and ACR70 (n=32)	-2.05036 regression coefficient

Comparison: Analysis for association between DAS28-ESR and ACR20 at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and ACR50 at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and ACR70 at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and ACR20 at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and ACR50 at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and ACR70 at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and ACR20 at Week 52p-value: 0.0004ANOVA

Comparison: Analysis for association between DAS28-ESR and ACR50 at Week 52p-value: 0.0004ANOVA

Comparison: Analysis for association between DAS28-ESR and ACR70 at Week 52p-value: 0.0004ANOVA

Secondary

Association Between Disease Activity Parameters: CDAI and SDAI, Assessed Using Correlation Coefficient

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. Higher scores represent greater affectation due to disease activity. SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. Higher scores indicate greater affectation due to disease activity. Correlation coefficient for relationship between CDAI and SDAI at different time points is reported. Correlation coefficient value range= -1 to 1. Higher positive value indicates greater positive relationship and higher negative value indicates greater negative relationship.

Time frame: Weeks 2, 24, 52

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Association Between Disease Activity Parameters: CDAI and SDAI, Assessed Using Correlation Coefficient	Week 2 (n=213)	0.98602 correlation coefficient
Tocilizumab	Association Between Disease Activity Parameters: CDAI and SDAI, Assessed Using Correlation Coefficient	Week 24 (n=185)	0.97515 correlation coefficient
Tocilizumab	Association Between Disease Activity Parameters: CDAI and SDAI, Assessed Using Correlation Coefficient	Week 52 (n=31)	0.97389 correlation coefficient

Comparison: Analysis for association between CDAI and SDAI at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and SDAI at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between CDAI and SDAI at Week 52p-value: <0.0001ANOVA

Secondary

Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient

The SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. EULAR response criteria (based on DAS28 score): Good responders (change from baseline \>1.2 with DAS28 \</=3.2); Moderate responders (change from baseline \>1.2 with DAS28 \>3.2 to \</=5.1 or change from baseline \>0.6 to \</=1.2 with DAS28 \</=5.1); Non-responders (change from baseline \</=0.6 or change from baseline \>0.6 and \</=1.2 with DAS28 \>5.1). Regression coefficient for relationship between SDAI and EULAR Good response at different time points is reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Time frame: Weeks 2, 24, 52

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Week 2: SDAI and EULAR (n=213)	-11.73463 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Week 24: SDAI and EULAR (n=185)	-7.32435 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient	Week 52: SDAI and EULAR (n=31)	-9.64146 regression coefficient

Comparison: Analysis for association between SDAI and EULAR at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between SDAI and EULAR at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between SDAI and EULAR at Week 52p-value: 0.0016ANOVA

Secondary

Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient

SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. The ACR 20, 50, and 70 responses: \>/=20%, 50%, and 70% improvement in TJC and SJC, and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit. Regression coefficients for relationship between SDAI and ACR responses (ACR20, ACR50, and ACR70) at different time points are reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Time frame: Weeks 2, 24, 52

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 24: SDAI and ACR20 (n=185)	-14.19790 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 2: SDAI and ACR20 (n=213)	-9.44923 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 2: SDAI and ACR50 (n=213)	-10.74230 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 2: SDAI and ACR70 (n=213)	-13.31421 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 24: SDAI and ACR50 (n=185)	-12.65454 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 24: SDAI and ACR70 (n=185)	-11.78067 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 52: SDAI and ACR20 (n=31)	-22.83519 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 52: SDAI and ACR50 (n=31)	-22.83519 regression coefficient
Tocilizumab	Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient	Week 52: SDAI and ACR70 (n=31)	-22.83519 regression coefficient

Comparison: Analysis for association between SDAI and ACR20 at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between SDAI and ACR50 at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between SDAI and ACR70 at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between SDAI and ACR20 at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between SDAI and ACR50 at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between SDAI and ACR70 at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between SDAI and ACR20 at Week 52p-value: <0.0001ANOVA

Comparison: Analysis for association between SDAI and ACR50 at Week 52p-value: <0.0001ANOVA

Comparison: Analysis for association between SDAI and ACR70 at Week 52p-value: <0.0001ANOVA

Secondary

Association Between Disease Activity Parameters: DAS28-ESR and CDAI, Assessed Using Correlation Coefficient

DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. Higher scores indicate greater affectation due to disease activity. The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. Higher scores represent greater affectation due to disease activity. Correlation coefficient for relationship between DAS28-ESR and CDAI at different time points is reported. Correlation coefficient value range= -1 to 1. Higher positive value indicates greater positive relationship and higher negative value indicates greater negative relationship.

Time frame: Weeks 2, 24, 52

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Association Between Disease Activity Parameters: DAS28-ESR and CDAI, Assessed Using Correlation Coefficient	Week 2 (n=213)	0.86514 correlation coefficient
Tocilizumab	Association Between Disease Activity Parameters: DAS28-ESR and CDAI, Assessed Using Correlation Coefficient	Week 24 (n=182)	0.86944 correlation coefficient
Tocilizumab	Association Between Disease Activity Parameters: DAS28-ESR and CDAI, Assessed Using Correlation Coefficient	Week 52 (n=32)	0.87301 correlation coefficient

Comparison: Analysis for association between DAS28-ESR and CDAI at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and CDAI at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and CDAI at Week 52p-value: <0.0001ANOVA

Secondary

Association Between Disease Activity Parameters: DAS28-ESR and SDAI, Assessed Using Correlation Coefficient

DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. Higher scores indicate greater affectation due to disease activity. SDAI is a numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. Higher scores indicate greater affectation due to disease activity. Correlation coefficient for relationship between DAS28-ESR and SDAI at different time points is reported. Correlation coefficient value range= -1 to 1. Higher positive value indicates greater positive relationship and higher negative value indicates greater negative relationship.

Time frame: Weeks 2, 24, 52

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Association Between Disease Activity Parameters: DAS28-ESR and SDAI, Assessed Using Correlation Coefficient	Week 2 (n=213)	0.88118 correlation coefficient
Tocilizumab	Association Between Disease Activity Parameters: DAS28-ESR and SDAI, Assessed Using Correlation Coefficient	Week 24 (n=182)	0.87060 correlation coefficient
Tocilizumab	Association Between Disease Activity Parameters: DAS28-ESR and SDAI, Assessed Using Correlation Coefficient	Week 52 (n=31)	0.81995 correlation coefficient

Comparison: Analysis for association between DAS28-ESR and SDAI at Week 2p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and SDAI at Week 24p-value: <0.0001ANOVA

Comparison: Analysis for association between DAS28-ESR and SDAI at Week 52p-value: <0.0001ANOVA

Secondary

Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52

DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hour) and PtGDA assessed on 0-10 cm VAS. Higher scores indicate greater affectation due to disease activity. DAS28-ESR total score= 0-9.4. DAS28-ESR \</=3.2 indicates low disease activity, DAS28-ESR \>3.2 to 5.1 indicates moderate to high disease activity, and DAS28-ESR \</=3.2 indicates remission.

Time frame: Baseline, Weeks 2, 24, and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52	Baseline (n=216)	5.81 units on a scale	Standard Deviation 1.08
Tocilizumab	Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52	Change at Week 2 (n=208)	-1.5 units on a scale	Standard Deviation 1.04
Tocilizumab	Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52	Change at Week 24 (n=174)	-3.2 units on a scale	Standard Deviation 1.47
Tocilizumab	Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52	Change at Week 52 (n=31)	-3.6 units on a scale	Standard Deviation 1.18

Comparison: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Secondary

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52

FACIT total score is sum of Functional Assessment of Cancer Therapy-General (FACT-G) score and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; additional concerns) score. FACT-G is a core questionnaire that evaluates quality of life (QoL) in cancer population. FACT-G consists of 27 questions grouped in 4 domains of general health-related QoL: physical well-being, social/family well-being, emotional well-being, and functional well-being; each item ranges from 0 (not at all) to 4 (very much). FACT-G score ranges between 0-108. FACIT-F is a 13-item questionnaire that evaluates self-reported fatigue and its impact upon daily activities. Each item ranges from 0 (Not at all) to 4 (Very much). The sum of all responses result in the FACIT total score with a total possible range of 0 (better score) to 160 (worse score). Negative change from baseline represents a better QoL.

Time frame: Baseline, Weeks 2, 24, and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52	Baseline (n=207)	72.41 units on a scale	Standard Deviation 16.806
Tocilizumab	Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52	Change at Week 2 (n=196)	-5.8 units on a scale	Standard Deviation 14.1
Tocilizumab	Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52	Change at Week 24 (n=165)	-11.1 units on a scale	Standard Deviation 18.6
Tocilizumab	Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52	Change at Week 52 (n=60)	-43.8 units on a scale	Standard Deviation 34.87

Comparison: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Secondary

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52

HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Time frame: Baseline, Weeks 2, 24, and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52	Baseline (n=223)	1.04 units on a scale	Standard Deviation 0.687
Tocilizumab	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52	Change at Week 2 (n=215)	-0.2 units on a scale	Standard Deviation 0.44
Tocilizumab	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52	Change at Week 24 (n=183)	-0.4 units on a scale	Standard Deviation 0.63
Tocilizumab	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52	Change at Week 52 (n=31)	-0.5 units on a scale	Standard Deviation 0.69

Comparison: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Secondary

Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52

The physician assessed participant's current disease activity on a 0-100 mm VAS, where 0 mm = no disease activity and 100 mm = maximum disease activity.

Time frame: Baseline, Weeks 2, 24, and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52	Baseline (n=226)	57.36 mm	Standard Deviation 19.228
Tocilizumab	Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52	Change at Week 2 (n=220)	-15.3 mm	Standard Deviation 17.49
Tocilizumab	Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52	Change at Week 24 (n=186)	-38.0 mm	Standard Deviation 25.13
Tocilizumab	Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52	Change at Week 52 (n=32)	-43.9 mm	Standard Deviation 17.13

Comparison: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Secondary

Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) at Weeks 24 and 52

PSQI is a questionnaire with 18 questions to assess sleep quality. The 18 questions are distributed to 7 elements (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction). A participant indicates how frequently each item was experienced on a scale from 0 to 3. The global score is the sum score of all 7 elements and ranges from 0-21 with higher values indicating worse sleep quality. A score of \>/=5 indicates poor sleepers.

Time frame: Baseline, Weeks 24 and 52

Population: Per-protocol analysis set (PPAS) included all participants in FAS without any major protocol violation and who completed 24 weeks of treatment period. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome; 'n'=participants evaluable at specified time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) at Weeks 24 and 52	Baseline (n=103)	11.00 units on a scale	Standard Deviation 2.719
Tocilizumab	Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) at Weeks 24 and 52	Change at Week 24 (n=73)	-0.7 units on a scale	Standard Deviation 2.39
Tocilizumab	Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) at Weeks 24 and 52	Change at Week 52 (n=16)	-0.9 units on a scale	Standard Deviation 2.42

Comparison: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: 0.0045Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: 0.1992Wilcoxon Rank Sum and Signed Rank Tests

Secondary

Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52

Participants answered the following question: Considering all the ways your arthritis affects you, how are you feeling today. Participants responded by using a 0 - 100 millimeter (mm) VAS, where 0 mm = very well and 100 mm = very poorly.

Time frame: Baseline, Weeks 2, 24, and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52	Baseline (n=226)	61.31 mm	Standard Deviation 23.526
Tocilizumab	Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52	Change at Week 2 (n=220)	-10.6 mm	Standard Deviation 20.99
Tocilizumab	Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52	Change at Week 24 (n=186)	-28.4 mm	Standard Deviation 27.4
Tocilizumab	Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52	Change at Week 52 (n=32)	-38.4 mm	Standard Deviation 27.65

Comparison: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Secondary

Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52

SDAI is a numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and C-reactive protein (CRP) in milligrams per deciliter (mg/dL). Higher scores indicate greater affectation due to disease activity. SDAI total score = 0-86. 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: Baseline, Weeks 2, 24, and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52	Baseline (n=215)	48.70 units on a scale	Standard Deviation 45.79
Tocilizumab	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52	Change at Week 2 (n=203)	-26.5 units on a scale	Standard Deviation 44.04
Tocilizumab	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52	Change at Week 24 (n=176)	-38.9 units on a scale	Standard Deviation 48.75
Tocilizumab	Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52	Change at Week 52 (n=29)	-39.3 units on a scale	Standard Deviation 26.82

Comparison: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Secondary

Change From Baseline in Total SJC at Weeks 2, 24, and 52

SJC was defined as the total number of swollen joints based on 66-joint assessment (SJC-66) and 28-joint assessment (SJC-28).

Time frame: Baseline, Weeks 2, 24, and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in Total SJC at Weeks 2, 24, and 52	SJC-28, Change at Week 2 (n=219)	-2.9 swollen joints	Standard Deviation 3.91
Tocilizumab	Change From Baseline in Total SJC at Weeks 2, 24, and 52	SJC-28, Change at Week 24 (n=189)	-6.7 swollen joints	Standard Deviation 5.17
Tocilizumab	Change From Baseline in Total SJC at Weeks 2, 24, and 52	SJC-28, Change at Week 52 (n=70)	-7.6 swollen joints	Standard Deviation 4.63
Tocilizumab	Change From Baseline in Total SJC at Weeks 2, 24, and 52	SJC-66, Baseline (n=223)	9.53 swollen joints	Standard Deviation 6.713
Tocilizumab	Change From Baseline in Total SJC at Weeks 2, 24, and 52	SJC-66, Change at Week 2 (n=218)	-3.7 swollen joints	Standard Deviation 4.94
Tocilizumab	Change From Baseline in Total SJC at Weeks 2, 24, and 52	SJC-66, Change at Week 24 (n=188)	-8.3 swollen joints	Standard Deviation 6.73
Tocilizumab	Change From Baseline in Total SJC at Weeks 2, 24, and 52	SJC-66, Change at Week 52 (n=69)	-9.1 swollen joints	Standard Deviation 6.66
Tocilizumab	Change From Baseline in Total SJC at Weeks 2, 24, and 52	SJC-28, Baseline (n=224)	7.90 swollen joints	Standard Deviation 5.203

Comparison: SJC-66: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: SJC-66: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: SJC-66: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: SJC-28: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: SJC-28: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: SJC-28: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Secondary

Change From Baseline in Total TJC at Weeks 2, 24, and 52

TJC was defined as the total number of painful joints based on 68-joint assessment (TJC-68) and 28-joint assessment (TJC-28).

Time frame: Baseline, Weeks 2, 24, and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Change From Baseline in Total TJC at Weeks 2, 24, and 52	TJC-68, Baseline (n=223)	16.91 tender joints	Standard Deviation 10.86
Tocilizumab	Change From Baseline in Total TJC at Weeks 2, 24, and 52	TJC-68, Change at Week 2 (n=218)	-5.4 tender joints	Standard Deviation 8.38
Tocilizumab	Change From Baseline in Total TJC at Weeks 2, 24, and 52	TJC-68, Change at Week 24 (n=188)	-12.9 tender joints	Standard Deviation 11.18
Tocilizumab	Change From Baseline in Total TJC at Weeks 2, 24, and 52	TJC-68, Change at Week 52 (n=69)	-16.5 tender joints	Standard Deviation 10.35
Tocilizumab	Change From Baseline in Total TJC at Weeks 2, 24, and 52	TJC-28, Baseline (n=224)	11.32 tender joints	Standard Deviation 6.241
Tocilizumab	Change From Baseline in Total TJC at Weeks 2, 24, and 52	TJC-28, Change at Week 2 (n=219)	-3.7 tender joints	Standard Deviation 5.4
Tocilizumab	Change From Baseline in Total TJC at Weeks 2, 24, and 52	TJC-28, Change at Week 24 (n=189)	-8.6 tender joints	Standard Deviation 6.62
Tocilizumab	Change From Baseline in Total TJC at Weeks 2, 24, and 52	TJC-28, Change at Week 52 (n=70)	-11.0 tender joints	Standard Deviation 6.14

Comparison: TJC-68: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: TJC-68: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: TJC-68: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: TJC-28: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: TJC-28: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: TJC-28: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Secondary

Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration

Time frame: Baseline, Weeks 12, 24, 38, 52, at early withdrawal (up to Week 52), at Follow-up Visit 2 (Week 76)

Population: FAS; Here 'n' signifies the number of participants evaluable at specified time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration	Baseline (n=213)	43.6 nanograms per milliliter (ng/mL)	Standard Deviation 49.3
Tocilizumab	Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration	Week 12 (n=189)	543.9 nanograms per milliliter (ng/mL)	Standard Deviation 144.34
Tocilizumab	Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration	Week 24 (n=181)	536.3 nanograms per milliliter (ng/mL)	Standard Deviation 144.32
Tocilizumab	Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration	Week 38 (n=171)	557.8 nanograms per milliliter (ng/mL)	Standard Deviation 144.23
Tocilizumab	Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration	Week 52 (n=168)	539.4 nanograms per milliliter (ng/mL)	Standard Deviation 147.04
Tocilizumab	Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration	Early Withdrawal (up to Week 52) (n=32)	329.1 nanograms per milliliter (ng/mL)	Standard Deviation 257.3
Tocilizumab	Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration	Follow-up Visit 2 (Week 76) (n=18)	523.4 nanograms per milliliter (ng/mL)	Standard Deviation 161.14

Secondary

Mean Tocilizumab Concentration

Time frame: Baseline, Weeks 12, 24, 38, 52, at early withdrawal (up to Week 52), at Follow-up Visit 2 (Week 76)

Population: FAS; Here 'n' signifies the number of participants evaluable at specified time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Mean Tocilizumab Concentration	Baseline (n=2)	35.6 micrograms per milliliter (mcg/mL)	Standard Deviation 48.89
Tocilizumab	Mean Tocilizumab Concentration	Week 12 (n=186)	46.4 micrograms per milliliter (mcg/mL)	Standard Deviation 23.01
Tocilizumab	Mean Tocilizumab Concentration	Week 24 (n=177)	52.6 micrograms per milliliter (mcg/mL)	Standard Deviation 28.21
Tocilizumab	Mean Tocilizumab Concentration	Week 38 (n=169)	55.2 micrograms per milliliter (mcg/mL)	Standard Deviation 30.55
Tocilizumab	Mean Tocilizumab Concentration	Week 52 (n=165)	54.0 micrograms per milliliter (mcg/mL)	Standard Deviation 29
Tocilizumab	Mean Tocilizumab Concentration	Early Withdrawal (up to Week 52) (n=19)	24.8 micrograms per milliliter (mcg/mL)	Standard Deviation 22.9
Tocilizumab	Mean Tocilizumab Concentration	Follow-up Visit 2 (Week 76) (n=17)	49.2 micrograms per milliliter (mcg/mL)	Standard Deviation 34.05

Secondary

Missed Working Days Assessed Using Short Form-Health and Labor Questionnaire (SF-HLQ) Score at Weeks 24 and 52

The SF-HLQ assessed productivity losses related to health problems in individuals with paid or unpaid work and consisted of three modules (absenteeism from paid work, production losses without absenteeism from paid work and hindrance in the performance of paid and unpaid work). Any missed working days or number of worked days with reduced efficiency during the last month were reported.

Time frame: Weeks 24 and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Missed Working Days Assessed Using Short Form-Health and Labor Questionnaire (SF-HLQ) Score at Weeks 24 and 52	Week 24 (n=69)	6.4 days	Standard Deviation 45.09
Tocilizumab	Missed Working Days Assessed Using Short Form-Health and Labor Questionnaire (SF-HLQ) Score at Weeks 24 and 52	Week 52 (n=7)	0.3 days	Standard Deviation 0.76

Secondary

Number of Participants Achieving Clinical Remission According to CDAI up to Week 52

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 during any two consecutive visits, not including the baseline visit indicates disease remission.

Time frame: Baseline up to Week 52 (Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 38, and 52)

Population: FAS

Arm	Measure	Value (NUMBER)
Tocilizumab	Number of Participants Achieving Clinical Remission According to CDAI up to Week 52	10 participants

Secondary

Participant Pain VAS Score at Weeks 2, 24, and 52

Participants assessed their pain using a 0-100 mm VAS. Intensity of pain range (over past week): 0 mm = no pain to 100 mm = worst possible pain.

Time frame: Weeks 2, 24, and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Participant Pain VAS Score at Weeks 2, 24, and 52	Baseline (n=226)	58.21 mm	Standard Deviation 23.622
Tocilizumab	Participant Pain VAS Score at Weeks 2, 24, and 52	Change at Week 2 (n=220)	-11.4 mm	Standard Deviation 22.38
Tocilizumab	Participant Pain VAS Score at Weeks 2, 24, and 52	Change at Week 24 (n=186)	-26.5 mm	Standard Deviation 27.31
Tocilizumab	Participant Pain VAS Score at Weeks 2, 24, and 52	Change at Week 52 (n=32)	-36.0 mm	Standard Deviation 26.82

Comparison: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Comparison: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.p-value: <0.0001Wilcoxon Rank Sum and Signed Rank Tests

Secondary

Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons

Percentage of DMARDs dose reduction and/or discontinuation (Red/Dis) events is reported by different reasons.

Time frame: Baseline up to Week 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants with DMARDs dose reductions and/or discontinuation.

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Safety	27.7 percentage of events
Tocilizumab	Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Discomfort	9.5 percentage of events
Tocilizumab	Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Lack of Efficacy	29.7 percentage of events
Tocilizumab	Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Other Than Above	31.1 percentage of events
Tocilizumab	Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Unknown	2.0 percentage of events

Secondary

Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons

Percentage of Non-DMARDs dose reduction and/or discontinuation (Red/Dis) events is reported by different reasons.

Time frame: Baseline up to Week 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants with non-DMARDs dose reductions and/or discontinuation.

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Safety	9.5 percentage of events
Tocilizumab	Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Discomfort	1.3 percentage of events
Tocilizumab	Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Lack of Efficacy	8.8 percentage of events
Tocilizumab	Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Other Than Above	73.7 percentage of events
Tocilizumab	Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons	Unknown	6.8 percentage of events

Secondary

Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response

The ACR 20, 50, and 70 responses: greater than or equal to (\>/=) 20 percent (%), 50%, and 70% improvement in TJC and SJC (28 assessed joints), and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP or ESR at each visit.

Time frame: Weeks 2, 24, and 52

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	Week 52: ACR 70 (n=70)	40.0 percentage of participants
Tocilizumab	Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	Week 2: ACR 20 (n=222)	18.5 percentage of participants
Tocilizumab	Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	Week 2: ACR 50 (n=222)	6.3 percentage of participants
Tocilizumab	Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	Week 2: ACR 70 (n=222)	11.7 percentage of participants
Tocilizumab	Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	Week 24: ACR 20 (n=192)	8.3 percentage of participants
Tocilizumab	Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	Week 24: ACR 50 (n=192)	4.7 percentage of participants
Tocilizumab	Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	Week 24: ACR 70 (n=192)	65.6 percentage of participants
Tocilizumab	Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	Week 52: ACR 20 (n=70)	0.0 percentage of participants
Tocilizumab	Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	Week 52: ACR 50 (n=70)	0.0 percentage of participants

Secondary

Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab

Percentage of participants with positive results for ATA against tocilizumab at different time points is reported.

Time frame: Baseline, Weeks 12, 24, 38, 52, at 8 weeks after last dose (up to Week 60), at early withdrawal (up to Week 52), at Follow-up Visits 1 (Week 64), 2 (Week 76), and 3 (Week 88)

Population: FAS; Here, 'n' signifies the number of participants evaluable at specified time point.

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab	Follow-up Visit 3 (Week 88) (n=3)	100.0 percentage of participants
Tocilizumab	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab	Baseline (n=227)	2.6 percentage of participants
Tocilizumab	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab	Week 12 (n=6)	100.0 percentage of participants
Tocilizumab	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab	Week 24 (n=179)	1.7 percentage of participants
Tocilizumab	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab	Week 38 (n=6)	33.3 percentage of participants
Tocilizumab	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab	Week 52 (n=161)	1.2 percentage of participants
Tocilizumab	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab	8 Weeks After Last Dose (up to Week 60) (n=41)	2.4 percentage of participants
Tocilizumab	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab	Early Withdrawal (up to Week 52) (n=31)	6.5 percentage of participants
Tocilizumab	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab	Follow-up Visit 1 (Week 64) (n=16)	100.0 percentage of participants
Tocilizumab	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab	Follow-up Visit 2 (Week 76) (n=11)	100.0 percentage of participants

Secondary

Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28

The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 \</=3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to \</=5.1 or change from baseline \>0.6 to \</=1.2 with DAS28 \</=5.1; non-responders: change from baseline \</=0.6 or change from baseline \>0.6 and \</=1.2 with DAS28 \>5.1.

Time frame: Baseline, Weeks 2, 24, and 52

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	Week 2: No Response (n=222)	32.4 percentage of participants
Tocilizumab	Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	Week 2: Moderate Response (n=222)	50.5 percentage of participants
Tocilizumab	Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	Week 2: Good Response (n=222)	17.1 percentage of participants
Tocilizumab	Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	Week 24: No Response (n=192)	13.5 percentage of participants
Tocilizumab	Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	Week 24: Moderate Response (n=192)	25.0 percentage of participants
Tocilizumab	Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	Week 24: Good Response (n=192)	61.5 percentage of participants
Tocilizumab	Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	Week 52: No Response (n=70)	55.7 percentage of participants
Tocilizumab	Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	Week 52: Moderate Response (n=70)	8.6 percentage of participants
Tocilizumab	Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	Week 52: Good Response (n=70)	35.7 percentage of participants

Secondary

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) of Special Interest

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are AEs occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state. Following AEs were considered as AEs of special interest: anaphylactic reaction, hypersensitivity, stress cardiomyopathy, Gilbert's syndrome, gastrointestinal perforation, injection site erythema, injection site hypersensitivity, injection site irritation, injection site pruritus, arthritis bacterial, cellulitis, klebsiella infection, oral candidiasis, pneumonia, skin infection, vulvovaginal candidiasis, alanine aminotransferase increased, hepatic enzyme increased, brain neoplasm malignant, and urticaria.

Time frame: Baseline up to 95 weeks

Population: FAS

Arm	Measure	Value (NUMBER)
Tocilizumab	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) of Special Interest	7.5 percentage of participants

Secondary

Treatment Compliance, as Assessed Using Participant Diary Cards and Return Records

Treatment Compliance was calculated as (total actual doses taken for the period) / (total planned or prescribed dose for the period) x 100.

Time frame: Weeks 24 and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tocilizumab	Treatment Compliance, as Assessed Using Participant Diary Cards and Return Records	Week 24 (n=221)	94.9 percentage of planned dose	Standard Deviation 10.2
Tocilizumab	Treatment Compliance, as Assessed Using Participant Diary Cards and Return Records	Week 52 (n=222)	94.7 percentage of planned dose	Standard Deviation 10.12

Source: ClinicalTrials.gov · Data processed: Feb 25, 2026

A Study to Evaluate Efficacy of Tocilizumab Administered as Monotherapy or in Combination With Methotrexate and/or Other Disease Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis (RA) Participants

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in CDAI at Week 12

Change From Baseline in CDAI at Week 16

Change From Baseline in CDAI at Week 2

Change From Baseline in CDAI at Week 20

Change From Baseline in CDAI at Week 4

Change From Baseline in CDAI at Week 8

Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24

Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient

Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient

Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient

Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient

Association Between Disease Activity Parameters: CDAI and SDAI, Assessed Using Correlation Coefficient

Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient

Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient

Association Between Disease Activity Parameters: DAS28-ESR and CDAI, Assessed Using Correlation Coefficient

Association Between Disease Activity Parameters: DAS28-ESR and SDAI, Assessed Using Correlation Coefficient

Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52

Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52

Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) at Weeks 24 and 52

Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52

Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52

Change From Baseline in Total SJC at Weeks 2, 24, and 52

Change From Baseline in Total TJC at Weeks 2, 24, and 52

Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration

Mean Tocilizumab Concentration

Missed Working Days Assessed Using Short Form-Health and Labor Questionnaire (SF-HLQ) Score at Weeks 24 and 52

Number of Participants Achieving Clinical Remission According to CDAI up to Week 52

Participant Pain VAS Score at Weeks 2, 24, and 52

Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons

Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons

Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response

Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab

Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) of Special Interest

Treatment Compliance, as Assessed Using Participant Diary Cards and Return Records