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

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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

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 positive results for ATA against tocilizumab at different time points is reported.