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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01941940
• Collaborator: (none)
• Enrollment: 227
• Locations: 49
• Arm: 1
• Actual Duration (Months): 34
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Tocilizumab; Drug: DMARDs	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 227 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Sep 5, 2013
• Actual Primary Completion Date: Sep 9, 2015
• Actual Study Completion Date: Jul 5, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Tocilizumab Tocilizumab at a fixed dose of 162 milligrams (mg) will be administered as subcutaneous (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 can continue the study treatment with SC tocilizumab until it becomes commercially available in Italy.

Drug: Tocilizumab; Tocilizumab at a fixed dose of 162 mg as SC injection will be administered once every week.; Other Names: RoActemra ; Drug: DMARDs; Non-biologic DMARDs according to standard of care, at a stable dose that was initiated at least 4 weeks prior to baseline.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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).

7. 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).

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. Mean Tocilizumab Concentration [Baseline, Weeks 12, 24, 38, 52, at early withdrawal (up to Week 52), at Follow-up Visit 2 (Week 76)]

30. 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)]

Eligibility Criteria

Criteria

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Uni Degli Studi Di L Aquila; Cattedra Di Reumatologia - Dept. Di Medicina Interna E San	Coppito	Abruzzo	Italy	67100
2	P. O. Spirito Santo - Asl Pescara; U.O. Complessa Di Reumatologia	Pescara	Abruzzo	Italy	65100
3	Azienda Ospedaliera Bianchi Melacrino Morelli; Unità Operativa di Reumatologia	Reggio Calabria	Calabria	Italy	89133
4	Az. Ospedaliera S. Giuseppe Moscati; Dip. Med. Gen. Struttura Semplice Reumatologia	Avellino	Campania	Italy	83100
5	Azienda Ospedaliera Rummo; Divisione Di Reumatologia	Benevento	Campania	Italy	82100
6	Azienda Ospedaliera A. Cardarelli; Medicina III - Divisione di Reumatologia	Napoli	Campania	Italy	80131
7	Policlinico Universitario-II Università di Napoli; Reumatologia	Napoli	Campania	Italy	80131
8	Osp Riuniti S.Giovanni di Dio e Ruggi d'Aragona; Rep. Medicina Interna	Salerno	Campania	Italy	84131
9	Irccs Fondazione Salvatore Maugeri-Istituto Scientifico Di Telese;U.O. Riabilitazione Reumatologica	Telese Terme	Campania	Italy	82037
10	A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2	Bologna	Emilia-Romagna	Italy	40138
11	A.O. Universitaria Policlinico Di Modena; Reumatologia	Modena	Emilia-Romagna	Italy	41100
12	Arcispedale Santa Maria Nuova; Reumatologia	Reggio Emilia	Emilia-Romagna	Italy	42100
13	Policlinico Univ. Uni Degli Sudi Di Udine; Clinica Di Reumatologia	Udine	Friuli-Venezia Giulia	Italy	33100
14	Policlinico Campus Bio-Medico Di Trigoria; Medicina Clinica E Reumatologia	Roma	Lazio	Italy	00128
15	Policlinico Tor Vergata; Divisione Di Reumatologia	Roma	Lazio	Italy	00133
16	Ospedale S.Pietro Fatebenefratelli; Divisione di Reumatologia	Roma	Lazio	Italy	00189
17	Ospedale La Colletta; Reparto Di Reumatologia	Arenzano	Liguria	Italy	16011
18	Università Degli Studi Di Genova - Dimi; Reumatologia	Genova	Liguria	Italy	16132
19	Ospedale San Paolo; Divisione di Reumatologia	Savona	Liguria	Italy	17100
20	Asst Papa Giovanni XXIII; Dh Reumatologia	Bergamo	Lombardia	Italy	24127
21	Ospedale Civile "La Memoria" Di Gavardo;Immunoematologia Trasfusionale-Allergologia E Reumatologia	Gavardo	Lombardia	Italy	25085
22	Ospedale Di Magenta Fornaroli; U.O. Di Reumatologia	Magenta	Lombardia	Italy	20013
23	Asst Centro Specialistico Ortopedico Traumato-Logico Gaetano Pini/Cto; Divisione Di Reumatologia	Milano	Lombardia	Italy	20122
24	Ospedale Maggiore Policlinico; Unità Operativa Complessa di Allergologia e Immunologia Clinica	Milano	Lombardia	Italy	20122
25	ASST FATEBENEFRATELLI SACCO; Reumatologia (Sacco)	Milano	Lombardia	Italy	20157
26	Asst Grande Ospedale Metropolitano Niguarda; Reumatologia	Milano	Lombardia	Italy	20162
27	ASST DI MONZA; Reumatologia (Medicina I)	Monza	Lombardia	Italy	20052
28	Irccs Policlinico San Matteo; Reumatologia Adulti	Pavia	Lombardia	Italy	27100
29	ASST DI VIMERCATE; Medicina Generale	Vimercate	Lombardia	Italy	20059
30	Ospedale Regionale Torrette; SOD Clinica Medica del Dipartimento di Medicina Interna e Specialisti	Ancona	Marche	Italy	60020
31	Ospedale Murri - Universita Politecnica Delle Marche; Clinica Reumatologica Ii	Jesi	Marche	Italy	60035
32	Azienda Ospedaliera Maggiore Della Carita; Day Hospital Immunologia	Novara	Piemonte	Italy	28100
33	Azienda Ospedaliera San Giovanni Battista; Reparto Reumatologia	Torino	Piemonte	Italy	10126
34	Ordine Mauriziano Ospedale Umberto I; Centro Di Reumatologia	Torino	Piemonte	Italy	10128
35	Azienda Ospedaliera Policlinico; Servizio Reumatologia	Bari	Puglia	Italy	70124
36	ASL Lecce- Presidio Ospedaliero di Casarano-Servizio di Reumatologia ed Osteoporosi	Casarano (LE)	Puglia	Italy	73042
37	Ospedali Riuniti di Foggia; Dipartimento Medicina Interna Reumatologia	Foggia	Puglia	Italy	71100
38	Ospedali Riuniti Di Foggia; Struttura Di Reumatologia	Foggia	Puglia	Italy	71100
39	A.O. Universitaria Policlinico Monserrato Di Cagliari; Reumatologia I	Cagliari	Sardegna	Italy	09042
40	Azienda Ospedaliero Universitaria di Sassari; UOC Reumatologia	Sassari	Sardegna	Italy	07100
41	Ospedale Vittorio Emanuele Ii; U.O. Reumatologia Clinica Medica Condorelli	Catania	Sicilia	Italy	95124
42	Azienda Osped. Univ. Policlinico G. Martino; Centro Prevenzione E Cura Osteoporosi	Messina	Sicilia	Italy	98100
43	Arnas Ospedale Civico; Medicina Interna II	Palermo	Sicilia	Italy	90127
44	Ospedale Careggi Villa Monnatessa ; Sezione Di Reumatologia	Firenze	Toscana	Italy	50139
45	Az. Osp. Pisana Ospedale S. Chiara; U.O. Di Reumatologia	Pisa	Toscana	Italy	56100
46	Osp S. Maria Misericordia Dip. Medicina Clinica Sperimentale Cattedra Reumatologia	Perugia	Umbria	Italy	06122
47	Ospedale Regionale Umberto Parini; Reparto Endocrinologia e Diabetologia - Amb. Reumatologia	Aosta	Valle D'Aosta	Italy	11100
48	Azienda Ospedaliera Universitaria Borgo Trento; Dipartimento di Medicina Sezione di Reumatologia	Verona	Veneto	Italy	37126
49	Policlinico G.B. Rossi; Divisione Immunologia Clinica Sperimentale Medicina B	Verona	Veneto	Italy	37134

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01941940
• Other Study ID Numbers: ML28699; 2013-001569-17
• First Posted: Sep 13, 2013
• Last Update Posted: Jul 11, 2017
• Last Verified: Jun 1, 2017

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Tocilizumab
Arm/Group Description	Tocilizumab at a fixed dose of 162 milligrams (mg) was administered as subcutaneous (SC) injection alone or along with methotrexate and/or other non-biological Disease-Modifying Antirheumatic Drugs (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).
Period Title: Overall Study
STARTED	227
COMPLETED	194
NOT COMPLETED	33

Baseline Characteristics

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Overall Participants	227
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.7 (12.12)
Sex: Female, Male (Count of Participants)
Female	197 86.8%
Male	30 13.2%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	183
Mean (Standard Deviation) [units on a scale]	-21.6 (13.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

2. Primary Outcome

Title	Change From Baseline in CDAI at Week 20
Description	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 20

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	185
Mean (Standard Deviation) [units on a scale]	-21.3 (12.87)

3. Primary Outcome

Title	Change From Baseline in CDAI at Week 16
Description	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 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	191
Mean (Standard Deviation) [units on a scale]	-20.2 (12.53)

4. Primary Outcome

Title	Change From Baseline in CDAI at Week 12
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	198
Mean (Standard Deviation) [units on a scale]	-19.1 (12.46)

5. Primary Outcome

Title	Change From Baseline in CDAI at Week 8
Description	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 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	203
Mean (Standard Deviation) [units on a scale]	-17.7 (12.07)

6. Primary Outcome

Title	Change From Baseline in CDAI at Week 4
Description	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 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	212
Mean (Standard Deviation) [units on a scale]	-14.0 (11.57)

7. Primary Outcome

Title	Change From Baseline in CDAI at Week 2
Description	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 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	218
Mean (Standard Deviation) [units on a scale]	-9.1 (9.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	227
Number [participants]	10 4.4%

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	216
Baseline (n=216)	5.81 (1.080)
Change at Week 2 (n=208)	-1.5 (1.04)
Change at Week 24 (n=174)	-3.2 (1.47)
Change at Week 52 (n=31)	-3.6 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	215
Baseline (n=215)	48.70 (45.790)
Change at Week 2 (n=203)	-26.5 (44.04)
Change at Week 24 (n=176)	-38.9 (48.75)
Change at Week 52 (n=29)	-39.3 (26.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	222
Week 2: ACR 20 (n=222)	18.5 8.1%
Week 2: ACR 50 (n=222)	6.3 2.8%
Week 2: ACR 70 (n=222)	11.7 5.2%
Week 24: ACR 20 (n=192)	8.3 3.7%
Week 24: ACR 50 (n=192)	4.7 2.1%
Week 24: ACR 70 (n=192)	65.6 28.9%
Week 52: ACR 20 (n=70)	0.0 0%
Week 52: ACR 50 (n=70)	0.0 0%
Week 52: ACR 70 (n=70)	40.0 17.6%

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	222
Week 2: No Response (n=222)	32.4 14.3%
Week 2: Moderate Response (n=222)	50.5 22.2%
Week 2: Good Response (n=222)	17.1 7.5%
Week 24: No Response (n=192)	13.5 5.9%
Week 24: Moderate Response (n=192)	25.0 11%
Week 24: Good Response (n=192)	61.5 27.1%
Week 52: No Response (n=70)	55.7 24.5%
Week 52: Moderate Response (n=70)	8.6 3.8%
Week 52: Good Response (n=70)	35.7 15.7%

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	224
TJC-68, Baseline (n=223)	16.91 (10.860)
TJC-68, Change at Week 2 (n=218)	-5.4 (8.38)
TJC-68, Change at Week 24 (n=188)	-12.9 (11.18)
TJC-68, Change at Week 52 (n=69)	-16.5 (10.35)
TJC-28, Baseline (n=224)	11.32 (6.241)
TJC-28, Change at Week 2 (n=219)	-3.7 (5.40)
TJC-28, Change at Week 24 (n=189)	-8.6 (6.62)
TJC-28, Change at Week 52 (n=70)	-11.0 (6.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	TJC-68: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	TJC-68: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	TJC-68: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	TJC-28: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	TJC-28: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	TJC-28: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	224
SJC-66, Baseline (n=223)	9.53 (6.713)
SJC-66, Change at Week 2 (n=218)	-3.7 (4.94)
SJC-66, Change at Week 24 (n=188)	-8.3 (6.73)
SJC-66, Change at Week 52 (n=69)	-9.1 (6.66)
SJC-28, Baseline (n=224)	7.90 (5.203)
SJC-28, Change at Week 2 (n=219)	-2.9 (3.91)
SJC-28, Change at Week 24 (n=189)	-6.7 (5.17)
SJC-28, Change at Week 52 (n=70)	-7.6 (4.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	SJC-66: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	SJC-66: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	SJC-66: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	SJC-28: Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	SJC-28: Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	SJC-28: Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	213
Week 2 (n=213)	0.86514
Week 24 (n=182)	0.86944
Week 52 (n=32)	0.87301

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and CDAI at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and CDAI at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and CDAI at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	213
Week 2 (n=213)	0.88118
Week 24 (n=182)	0.87060
Week 52 (n=31)	0.81995

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and SDAI at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and SDAI at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and SDAI at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	213
Week 2 (n=213)	0.98602
Week 24 (n=185)	0.97515
Week 52 (n=31)	0.97389

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and SDAI at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and SDAI at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and SDAI at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	213
Week 2: DAS28-ESR and ACR20 (n=213)	-1.02676
Week 2: DAS28-ESR and ACR50 (n=213)	-1.31737
Week 2: DAS28-ESR and ACR70 (n=213)	-1.50400
Week 24: DAS28-ESR and ACR20 (n=182)	-1.71191
Week 24: DAS28-ESR and ACR50 (n=182)	-1.54281
Week 24: DAS28-ESR and ACR70 (n=182)	-1.43977
Week 52: DAS28-ESR and ACR20 (n=32)	-2.05036
Week 52: DAS28-ESR and ACR50 (n=32)	-2.05036
Week 52: DAS28-ESR and ACR70 (n=32)	-2.05036

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and ACR20 at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and ACR50 at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and ACR70 at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and ACR20 at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and ACR50 at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and ACR70 at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and ACR20 at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and ACR50 at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and ACR70 at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANOVA
	Comments

19. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	213
Week 2: DAS28-ESR and EULAR (n=213)	-1.62883
Week 24: DAS28-ESR and EULAR (n=182)	-1.36226
Week 52: DAS28-ESR and EULAR (n=32)	-1.47781

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and EULAR at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and EULAR at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between DAS28-ESR and EULAR at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

20. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	220
Week 2: CDAI and ACR20 (n=220)	-9.65473
Week 2: CDAI and ACR50 (n=220)	-10.67389
Week 2: CDAI and ACR70 (n=220)	-13.38810
Week 24: CDAI and ACR20 (n=186)	-13.18433
Week 24: CDAI and ACR50 (n=186)	-11.95933
Week 24: CDAI and ACR70 (n=186)	-11.18299
Week 52: CDAI and ACR20 (n=32)	-18.94643
Week 52: CDAI and ACR50 (n=32)	-18.94643
Week 52: CDAI and ACR70 (n=32)	-18.94643

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and ACR20 at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and ACR50 at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and ACR70 at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and ACR20 at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and ACR50 at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and ACR70 at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and ACR20 at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and ACR50 at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and ACR70 at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	220
Week 2: CDAI and EULAR (n=220)	-10.97686
Week 24: CDAI and EULAR (n=186)	-7.03184
Week 52: CDAI and EULAR (n=32)	-9.46563

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and EULAR at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and EULAR at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between CDAI and EULAR at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

22. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	213
Week 2: SDAI and ACR20 (n=213)	-9.44923
Week 2: SDAI and ACR50 (n=213)	-10.74230
Week 2: SDAI and ACR70 (n=213)	-13.31421
Week 24: SDAI and ACR20 (n=185)	-14.19790
Week 24: SDAI and ACR50 (n=185)	-12.65454
Week 24: SDAI and ACR70 (n=185)	-11.78067
Week 52: SDAI and ACR20 (n=31)	-22.83519
Week 52: SDAI and ACR50 (n=31)	-22.83519
Week 52: SDAI and ACR70 (n=31)	-22.83519

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and ACR20 at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and ACR50 at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and ACR70 at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and ACR20 at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and ACR50 at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and ACR70 at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and ACR20 at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and ACR50 at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and ACR70 at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

23. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	213
Week 2: SDAI and EULAR (n=213)	-11.73463
Week 24: SDAI and EULAR (n=185)	-7.32435
Week 52: SDAI and EULAR (n=31)	-9.64146

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and EULAR at Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and EULAR at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for association between SDAI and EULAR at Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	ANOVA
	Comments

24. Secondary Outcome

Title	Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons
Description	Percentage of DMARDs dose reduction and/or discontinuation (Red/Dis) events is reported by different reasons.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	79
Measure DMARDs Dose Red/Dis Events	148
Safety	27.7
Discomfort	9.5
Lack of Efficacy	29.7
Other Than Above	31.1
Unknown	2.0

25. Secondary Outcome

Title	Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons
Description	Percentage of Non-DMARDs dose reduction and/or discontinuation (Red/Dis) events is reported by different reasons.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	154
Measure Non-DMARDs Dose Red/Dis Events	547
Safety	9.5
Discomfort	1.3
Lack of Efficacy	8.8
Other Than Above	73.7
Unknown	6.8

26. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	226
Baseline (n=226)	61.31 (23.526)
Change at Week 2 (n=220)	-10.6 (20.99)
Change at Week 24 (n=186)	-28.4 (27.40)
Change at Week 52 (n=32)	-38.4 (27.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

27. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	226
Baseline (n=226)	57.36 (19.228)
Change at Week 2 (n=220)	-15.3 (17.49)
Change at Week 24 (n=186)	-38.0 (25.13)
Change at Week 52 (n=32)	-43.9 (17.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

28. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	226
Baseline (n=226)	58.21 (23.622)
Change at Week 2 (n=220)	-11.4 (22.38)
Change at Week 24 (n=186)	-26.5 (27.31)
Change at Week 52 (n=32)	-36.0 (26.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

29. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	223
Baseline (n=223)	1.04 (0.687)
Change at Week 2 (n=215)	-0.2 (0.44)
Change at Week 24 (n=183)	-0.4 (0.63)
Change at Week 52 (n=31)	-0.5 (0.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

30. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	69
Week 24 (n=69)	6.4 (45.09)
Week 52 (n=7)	0.3 (0.76)

31. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	207
Baseline (n=207)	72.41 (16.806)
Change at Week 2 (n=196)	-5.8 (14.10)
Change at Week 24 (n=165)	-11.1 (18.60)
Change at Week 52 (n=60)	-43.8 (34.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 2 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

32. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	103
Baseline (n=103)	11.00 (2.719)
Change at Week 24 (n=73)	-0.7 (2.39)
Change at Week 52 (n=16)	-0.9 (2.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 24 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0045
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tocilizumab
	Comments	Analysis for change from baseline to Week 52 was performed using Wilcoxon Rank Sum and Signed Rank Tests for dependent sample.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1992
	Comments
	Method	Wilcoxon Rank Sum and Signed Rank Tests
	Comments

33. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	222
Week 24 (n=221)	94.9 (10.20)
Week 52 (n=222)	94.7 (10.12)

34. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	227
Number [percentage of participants]	7.5 3.3%

35. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	227
Baseline (n=227)	2.6 1.1%
Week 12 (n=6)	100.0 44.1%
Week 24 (n=179)	1.7 0.7%
Week 38 (n=6)	33.3 14.7%
Week 52 (n=161)	1.2 0.5%
8 Weeks After Last Dose (up to Week 60) (n=41)	2.4 1.1%
Early Withdrawal (up to Week 52) (n=31)	6.5 2.9%
Follow-up Visit 1 (Week 64) (n=16)	100.0 44.1%
Follow-up Visit 2 (Week 76) (n=11)	100.0 44.1%
Follow-up Visit 3 (Week 88) (n=3)	100.0 44.1%

36. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	227
Baseline (n=2)	35.6 (48.89)
Week 12 (n=186)	46.4 (23.01)
Week 24 (n=177)	52.6 (28.21)
Week 38 (n=169)	55.2 (30.55)
Week 52 (n=165)	54.0 (29.00)
Early Withdrawal (up to Week 52) (n=19)	24.8 (22.90)
Follow-up Visit 2 (Week 76) (n=17)	49.2 (34.05)

37. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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).
Measure Participants	227
Baseline (n=213)	43.6 (49.30)
Week 12 (n=189)	543.9 (144.34)
Week 24 (n=181)	536.3 (144.32)
Week 38 (n=171)	557.8 (144.23)
Week 52 (n=168)	539.4 (147.04)
Early Withdrawal (up to Week 52) (n=32)	329.1 (257.30)
Follow-up Visit 2 (Week 76) (n=18)	523.4 (161.14)

Adverse Events

Time Frame	Day 1 up to approximately 95 weeks
Adverse Event Reporting Description	FAS; TEAEs are adverse events 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.
Arm/Group Title	Tocilizumab
Arm/Group Description	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).
All Cause Mortality
	Tocilizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tocilizumab
	Affected / at Risk (%)	# Events
Total	17/227 (7.5%)
Cardiac disorders
Stress cardiomyopathy	1/227 (0.4%)
Gastrointestinal disorders
Gastrointestinal perforation	1/227 (0.4%)
Immune system disorders
Anaphylactic reaction	1/227 (0.4%)
Infections and infestations
Pneumonia	1/227 (0.4%)
Skin infection	1/227 (0.4%)
Cellulitis	1/227 (0.4%)
Diverticulitis	1/227 (0.4%)
Klebsiella infection	1/227 (0.4%)
Injury, poisoning and procedural complications
Humerus fracture	1/227 (0.4%)
Wrist fracture	1/227 (0.4%)
Investigations
Carcinoembryonic antigen increased	1/227 (0.4%)
Hepatic enzyme increased	1/227 (0.4%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/227 (0.4%)
Product Issues
Device breakage	1/227 (0.4%)
Reproductive system and breast disorders
Ovarian cyst	1/227 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pleurisy	1/227 (0.4%)
Surgical and medical procedures
Bladder neoplasm surgery	1/227 (0.4%)
Vascular disorders
Aneurysm	1/227 (0.4%)
Other (Not Including Serious) Adverse Events
	Tocilizumab
	Affected / at Risk (%)	# Events
Total	36/227 (15.9%)
Infections and infestations
Influenza	23/227 (10.1%)
Bronchitis	15/227 (6.6%)
Urinary tract infection	12/227 (5.3%)
Investigations
Transaminases increased	15/227 (6.6%)
Respiratory, thoracic and mediastinal disorders
Cough	16/227 (7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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