Trial Outcomes & Findings for A Study to Assess the Effect of Tocilizumab + Methotrexate on Prevention of Structural Joint Damage in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA) (NCT NCT00106535)

Last Updated: 2014-02-06

Results Overview

ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1196 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2014-02-06

Participant Flow

This study was divided into two phases: a 2-year core placebo controlled treatment phase and an optional 3-year extension phase.

Participant milestones

Participant milestones
Measure	Placebo + Methotrexate Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with \< 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a \>70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab (TCZ) 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with \< 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a \>70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension (LTE) period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with \< 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a \>70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.	All Tocilizumab Exposure + MTX All tocilizumab (TCZ) exposure + methotrexate (MTX) group included all participants who received at least one dose of tocilizumab during the placebo controlled core study or the long term extension period plus MTX 10-25 mg (oral or parenteral) weekly. Participants received either Placebo, Tocilizumab 4 mg/kg or Tocilizumab 8 mg/kg in the 2 year placebo controlled core treatment phase. In the extension 3 to 5 year period, all participants received 8 mg/kg IV every 4 weeks.
2-year Placebo Controlled Period STARTED	394	401	401	0
2-year Placebo Controlled Period Intent-to-treat: Received Study Drug	393	399	398	0
2-year Placebo Controlled Period Safety: Actual Treatment Received	392	399	399	0
2-year Placebo Controlled Period Completed Week 24	356	373	366	0
2-year Placebo Controlled Period Completed Week 52	326	342	338	0
2-year Placebo Controlled Period COMPLETED	287	309	310	0
2-year Placebo Controlled Period NOT COMPLETED	107	92	91	0
Long-term Extension Period (Year 3 to 5) STARTED	0	0	0	894
Long-term Extension Period (Year 3 to 5) COMPLETED	0	0	0	704
Long-term Extension Period (Year 3 to 5) NOT COMPLETED	0	0	0	190

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Assess the Effect of Tocilizumab + Methotrexate on Prevention of Structural Joint Damage in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Total n=1190 Participants Total of all reporting groups
Age, Continuous	51.3 years STANDARD_DEVIATION 12.41 • n=5 Participants	51.4 years STANDARD_DEVIATION 12.59 • n=7 Participants	53.4 years STANDARD_DEVIATION 11.72 • n=5 Participants	52.0 years STANDARD_DEVIATION 12.24 • n=4 Participants
Sex: Female, Male Female	328 Participants n=5 Participants	336 Participants n=7 Participants	325 Participants n=5 Participants	989 Participants n=4 Participants
Sex: Female, Male Male	65 Participants n=5 Participants	63 Participants n=7 Participants	73 Participants n=5 Participants	201 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat (ITT) population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With American College of Rheumatology-ACR20 Response	27.0 Percentage of participants	50.6 Percentage of participants	56.3 Percentage of participants

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat (ITT) population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Linear extrapolation was used to impute missing week 52 data. Data collected after withdrawal or on escape therapy is excluded.

Radiographs were taken of each hand and foot at Baseline and Week 52 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 (normalized from 98) and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 (normalized from 104) and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=290 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=339 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=348 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Modified Total Sharp-Genant Score at Week 52	1.13 Score on a scale Standard Deviation 2.962	0.34 Score on a scale Standard Deviation 1.451	0.29 Score on a scale Standard Deviation 1.282

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing HAQ scores. All assessments were set to missing after a patient received escape therapy.

HAQ-DI consisted of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities rated on a 4-point scale where 0=without any difficulty to 3=unable to do. The sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst). Functional disability was determined as a cumulative measure of HAQ-DI over 1 year by using the AUC of the change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI indicate a greater average improvement in physical function over time and represent a decrease in sustained impairment. For patients with missing week 52 HAQ-DI score, the AUC of the change from baseline was standardized to 52 weeks using the latest timepoint available for calculation of the AUC. The mean was adjusted for region. A negative change from baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=366 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=376 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=374 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change in Physical Function as Measured by the Area Under the Curve (AUC) for the Change From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 52	-58.11 Score on a scale*week Full Range 150.839 • Interval -699.8 to 401.0	-128.37 Score on a scale*week Full Range 165.084 • Interval -1059.6 to 266.8	-144.06 Score on a scale*week Full Range 173.372 • Interval -895.7 to 323.7

PRIMARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Data collected after withdrawal or for patients on escape therapy the data is excluded. Missing data was imputed using linear extrapolation.

Radiographs of each hand and foot were taken at Baseline and Week 104 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=294 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=343 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=353 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in the Modified Total Sharp-Genant Score at Week 104	1.96 Score on a scale Standard Deviation 5.956	0.58 Score on a scale Standard Deviation 2.357	0.37 Score on a scale Standard Deviation 1.547

PRIMARY outcome

Timeframe: Baseline to Week 104

Population: Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing HAQ scores. For patients who received escape therapy, the HAQ-DI was set to missing from the time they entered escape.

HAQ-DI consisted of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities rated on a 4-point scale where 0=without any difficulty to 3=unable to do. The sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst). Functional disability was determined as a cumulative measure of HAQ-DI over 2 years by using the AUC of the change from baseline in HAQ-DI score through week 104. Decreases in AUC of change from baseline in HAQ-DI indicated a gr eater average improvement in physical function over time and represent a decrease in sustained impairment. For patients with missing week 104 HAQ-DI score, the AUC of the change from baseline was standardized to 104 weeks using the latest timepoint available for calculation of the AUC. A negative change from baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=366 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=376 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=374 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change in Physical Function as Measured by the Area Under the Curve for the Change From Baseline in the Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 104	-139.40 Score on a scale*week Full Range 365.682 • Interval -1503.9 to 801.9	-287.50 Score on a scale*week Full Range 383.201 • Interval -2145.6 to 630.8	-320.80 Score on a scale*week Full Range 385.741 • Interval -1776.6 to 677.2

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew prematurely or where an ACR could not be calculated, were set to 'Non Responder'.

ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With ACR50 Response	9.7 Percentage of participants	25.1 Percentage of participants	32.2 Percentage of participants

SECONDARY outcome

Timeframe: Baseline,Week 24

ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With ACR70 Response	2.0 Percentage of participants	11.0 Percentage of participants	12.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for swollen joint counts. All assessments were set to missing from the time a patient received escape therapy and only pre-escape therapy joint count assessments were carried forward.

66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Swollen Joint Count (66 Joint Count): Mean Change From Baseline at Week 24 Baseline Swollen Joint Count (SJC)	16.6 joint count Standard Deviation 9.23	17.0 joint count Standard Deviation 9.78	17.3 joint count Standard Deviation 9.48
Swollen Joint Count (66 Joint Count): Mean Change From Baseline at Week 24 Change from Baseline at Week 24 (n=391,399, 397)	-2.9 joint count Standard Deviation 10.37	-7.9 joint count Standard Deviation 9.31	-9.0 joint count Standard Deviation 9.76

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. LOCF was used for swollen joint counts. All assessments were set to missing from the time a patient received escape therapy and only pre-escape therapy joint count assessments were carried forward.

68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tender Joint Count (68 Joint Count): Mean Change From Baseline at Week 24 Change from Baseline at Week 24 (n=391,399, 397)	-4.8 joint count Standard Deviation 14.61	-12.2 joint count Standard Deviation 14.94	-14.2 joint count Standard Deviation 14.58
Tender Joint Count (68 Joint Count): Mean Change From Baseline at Week 24 Baseline Tender Joint Count (TJC)	27.9 joint count Standard Deviation 14.80	27.9 joint count Standard Deviation 14.15	29.3 joint count Standard Deviation 15.22

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. No imputation was used for missing VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

The patient's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Patient's Global Visual Analog Scale (VAS): Mean Change From Baseline at Week 24 Baseline Patient Visual Analog Scale (VAS)	63.1 millimeters (mm) Standard Deviation 23.36	61.0 millimeters (mm) Standard Deviation 23.25	62.7 millimeters (mm) Standard Deviation 22.49
Patient's Global Visual Analog Scale (VAS): Mean Change From Baseline at Week 24 Change from Baseline at Week 24 (n=213,308,316)	-17.5 millimeters (mm) Standard Deviation 26.60	-25.2 millimeters (mm) Standard Deviation 27.09	-25.2 millimeters (mm) Standard Deviation 24.95

SECONDARY outcome

Timeframe: Baseline, Week 24

The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Physician's Global VAS: Mean Change From Baseline at Week 24 Baseline Physician's Visual Analog Scale (VAS)	63.1 mm Standard Deviation 17.34	62.3 mm Standard Deviation 16.8	62.7 mm Standard Deviation 16.90
Physician's Global VAS: Mean Change From Baseline at Week 24 Change from Baseline at Week 24 (n=214,307,320)	-29.0 mm Standard Deviation 24.35	-36.1 mm Standard Deviation 24.31	-39.8 mm Standard Deviation 21.82

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. No imputation used for missing VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

The patient assessed their pain on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Patient's Pain VAS: Mean Change From Baseline at Week 24 Change from Baseline at Week 24 (n=213,308,317)	-12.5 mm Standard Deviation 24.92	-19.5 mm Standard Deviation 25.24	-21.8 mm Standard Deviation 25.93
Patient's Pain VAS: Mean Change From Baseline at Week 24 Baseline Patient Pain Visual Analog Scale (VAS)	55.3 mm Standard Deviation 22.07	53.3 mm Standard Deviation 21.97	55.7 mm Standard Deviation 22.34

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. No imputation was used for missing CRP. All assessments were set to missing from the time a patient received escape therapy.

The serum concentration of C-Reactive Protein (CRP) is measured in mg/dL. A reduction in the level is considered an improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
C-Reactive Protein (CRP): Mean Change From Baseline at Week 24 Baseline C-Reactive Protein (CRP)	2.235 milligrams/deciliter (mg/dL) Standard Deviation 2.5068	2.076 milligrams/deciliter (mg/dL) Standard Deviation 2.3892	2.337 milligrams/deciliter (mg/dL) Standard Deviation 2.6065
C-Reactive Protein (CRP): Mean Change From Baseline at Week 24 Change from Baseline at Week 24 (n=214,308,321)	-0.3560 milligrams/deciliter (mg/dL) Standard Deviation 2.12778	-0.9558 milligrams/deciliter (mg/dL) Standard Deviation 2.35222	-2.0699 milligrams/deciliter (mg/dL) Standard Deviation 2.50035

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. No imputation was used for missing ESR. All assessments were set to missing from the time a patient received escape therapy.

The Erythrocyte Sedimentation Rate (ESR) was measured in mm/hr. A reduction in the level is considered an improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Erythrocyte Sedimentation Rate: Mean Change From Baseline at Week 24 Baseline Erythrocyte Sedimentation Rate (ESR)	46.5 millimeters/hour (mm/hr) Standard Deviation 24.69	45.9 millimeters/hour (mm/hr) Standard Deviation 25.12	46.4 millimeters/hour (mm/hr) Standard Deviation 24.8
Erythrocyte Sedimentation Rate: Mean Change From Baseline at Week 24 Change from Baseline at Week 24 (n=211,304,318)	-9.5 millimeters/hour (mm/hr) Standard Deviation 24.01	-21.8 millimeters/hour (mm/hr) Standard Deviation 23.71	-36.8 millimeters/hour (mm/hr) Standard Deviation 24.12

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug, with data available for analysis. No imputation was used for missing HAQ-DI. All assessments were set to missing from the time a patient received escape therapy.

HAQ-DI is a self-completed patient questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Week 24 Baseline HAQ-DI	1.5 Scores on a scale Standard Deviation 0.62	1.5 Scores on a scale Standard Deviation 0.64	1.5 Scores on a scale Standard Deviation 0.60
Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Week 24 Change from Baseline at Week 24 (n=197,292,301)	-0.32 Scores on a scale Standard Deviation 0.516	-0.45 Scores on a scale Standard Deviation 0.531	-0.51 Scores on a scale Standard Deviation 0.580

SECONDARY outcome

Timeframe: Baseline, Week 52

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With American College of Rheumatology (ACR20) Response at Week 52	24.7 Percentage of participants	47.9 Percentage of participants	55.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 104

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With ACR20 Response at Week 104	29.3 Percentage of participants	49.1 Percentage of participants	54.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With ACR50 Response at Week 52	10.2 Percentage of participants	30.3 Percentage of participants	36.4 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 104

ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With ACR50 Response at Week 104	19.8 Percentage of participants	37.6 Percentage of participants	38.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With ACR70 Response at Week 52	3.8 Percentage of participants	16.5 Percentage of participants	20.1 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 104

ACR50 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With ACR70 Response at Week 104	12.2 Percentage of participants	24.3 Percentage of participants	22.4 Percentage of participants

SECONDARY outcome

Timeframe: 104 Weeks

ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With ACR70 Response Maintained for 6 Consecutive Months	5.6 Percentage of participants	11.5 Percentage of participants	14.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

66 joints were assessed at Baseline and Week 52 for swelling and joints are classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=391 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=397 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Swollen Joint Count at Week 52	-2.5 Joint count Standard Deviation 11.07	-8.0 Joint count Standard Deviation 9.95	-10.2 Joint count Standard Deviation 10.65

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for missing tender joint data. All assessments were set to missing from the time a patient received escape therapy and only pre-escape therapy joint count assessments were carried forward.

68 joints were assessed at Baseline and Week 52 for tenderness and joints were classified as tender/not tender for a total possible tender joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=391 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=397 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Tender Joint Count at Week 52	-4.1 Joint count Standard Deviation 15.53	-12.3 Joint count Standard Deviation 15.74	-15.6 Joint count Standard Deviation 16.04

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

The patient's global assessment of disease activity is assessed at Baseline and Week 52 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=156 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=248 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=281 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Patient's Global Assessment of Disease Activity at Week 52	-21.1 Score on a scale Standard Deviation 26.22	-27.2 Score on a scale Standard Deviation 28.83	-29.8 Score on a scale Standard Deviation 25.61

SECONDARY outcome

Timeframe: Baseline, Week 52

The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=155 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=246 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=279 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Physicians Global Assessment of Disease Activity at Week 52	-35.2 Score on a scale Standard Deviation 25.13	-42.2 Score on a scale Standard Deviation 23.57	-45.4 Score on a scale Standard Deviation 22.22

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing VAS assessments. Data was set to missing for patients who received escape therapy.

The patient assessed their pain at Baseline and Week 52 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=156 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=248 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=282 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in the Patient's Pain VAS at Week 52	-15.0 Score on a scale Standard Deviation 25.10	-22.9 Score on a scale Standard Deviation 25.70	-26.1 Score on a scale Standard Deviation 25.51

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was made for missing data. All assessments were set to missing from the time a patient received escape therapy.

Blood was collected for C-Reactive Protein (CRP) at Baseline and Week 52 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=157 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=247 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=282 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in C-Reactive Protein (CRP) at Week 52	-0.3800 mg/dL Standard Deviation 2.50681	-1.0615 mg/dL Standard Deviation 2.39897	-2.2584 mg/dL Standard Deviation 2.71950

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing data. Data was set to missing for patients who received escape therapy.

Blood was collected for Erythrocyte Sedimentation Rate (ESR) at Baseline and Week 52 and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=149 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=235 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=274 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52	-10.9 mm/hr Standard Deviation 24.27	-25.6 mm/hr Standard Deviation 24.68	-38.5 mm/hr Standard Deviation 24.31

SECONDARY outcome

Timeframe: Baseline, Week 104

66 joints were assessed at Baseline and Week 104 for swelling and joints were classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=391 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=397 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Swollen Joint Count at Week 104	-3.5 Joint count Standard Deviation 11.65	-9.0 Joint count Standard Deviation 10.76	-11.3 Joint count Standard Deviation 11.31

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender joint counts. All assessments were set to missing from the time a patient received escape therapy and only pre-escape therapy joint count assessments were carried forward.

68 joints were assessed for tenderness and joints were classified as tender/not tender for a total possible tender joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=391 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=397 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Tender Joint Count at Week 104	-5.9 Joint count Standard Deviation 17.07	-13.6 Joint count Standard Deviation 16.53	-17.7 Joint count Standard Deviation 16.73

SECONDARY outcome

Timeframe: Baseline, Week 104

The patient's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=137 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=228 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=248 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Patient's Global Assessment of Disease Activity at Week 104	-33.2 Score on a scale Standard Deviation 26.35	-31.6 Score on a scale Standard Deviation 27.05	-33.9 Score on a scale Standard Deviation 26.60

SECONDARY outcome

Timeframe: Baseline, Week 104

The physician's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=139 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=229 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=250 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Physicians Global Assessment of Disease Activity at Week 104	-43.9 Score on a scale Standard Deviation 21.55	-49.1 Score on a scale Standard Deviation 20.33	-48.7 Score on a scale Standard Deviation 22.20

SECONDARY outcome

Timeframe: Baseline, Week 104

The patient assessed their pain at Baseline and Week 104 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=137 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=228 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=248 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in the Patient's Pain VAS at Week 104	-25.6 Score on a scale Standard Deviation 24.44	-26.6 Score on a scale Standard Deviation 25.39	-28.9 Score on a scale Standard Deviation 25.47

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Blood was collected for C-Reactive Protein (CRP) at Baseline and Week 104 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=139 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=231 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=251 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in C-Reactive Protein (CRP) at Week 104	-1.6346 mg/dL Standard Deviation 2.28001	-1.6863 mg/dL Standard Deviation 2.20965	-2.3068 mg/dL Standard Deviation 2.65256

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Blood was collected for Erythrocyte Sedimentation Rate (ESR) at Baseline and Week 104 and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=139 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=231 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=247 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 104	-30.7 mm/hr Standard Deviation 22.26	-35.4 mm/hr Standard Deviation 25.07	-36.9 mm/hr Standard Deviation 23.39

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing for patients who received escape therapy.

The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do). HAQ-DI=sum of worst scores in each domain divided by the number of domains answered for a total possible score of 0 (best) to 3 (worst).

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=146 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=235 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=263 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 52	52.7 Percentage of participants	59.6 Percentage of participants	62.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered for a total possible score of 0 (best) to 3 (worst). .

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=127 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=218 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=231 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 104	58.3 Percentage of participants	63.3 Percentage of participants	62.3 Percentage of participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ score, CRP, ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 24. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=216 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=308 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=320 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Area Under Curve (AUC) of the ACRn to Week 24	609.11 Score on a scale*week Standard Deviation 5551.669	2791.49 Score on a scale*week Standard Deviation 5479.514	3528.89 Score on a scale*week Standard Deviation 5812.582

SECONDARY outcome

Timeframe: 52 Weeks

Population: Participants from the Intent-to-treat population(all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ score, CRP, ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 52. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=156 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=247 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=279 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Area Under Curve (AUC) of the ACRn to Week 52	5551.25 Score on a scale*week Full Range 6080.038 • Interval -49420.8 to 25818.8	10763.54 Score on a scale*week Full Range 7488.703 • Interval -74637.5 to 33589.0	12644.01 Score on a scale*week Full Range 7248.249 • Interval -13773.8 to 31246.7

SECONDARY outcome

Timeframe: 104 Weeks

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ score, CRP, ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 104. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=138 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=228 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=249 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Area Under Curve (AUC) of the ACRn Score at Week 104	21094.97 Score on a scale*week Standard Deviation 22341.489	27141.08 Score on a scale*week Standard Deviation 24296.659	30876.59 Score on a scale*week Standard Deviation 18177.420

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=208 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=301 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=311 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Disease Activity Score (DAS28) at Week 24	-1.49 Score on a scale Standard Deviation 1.257	-2.45 Score on a scale Standard Deviation 1.401	-3.28 Score on a scale Standard Deviation 1.383

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=153 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=247 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=273 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Disease Activity Score (DAS28) at Week 52	-1.88 Score on a scale Standard Deviation 1.319	-2.97 Score on a scale Standard Deviation 1.391	-3.80 Score on a scale Standard Deviation 1.263

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=134 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=223 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=238 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Disease Activity Score (DAS28) at Week 104	-3.70 Score on a scale Standard Deviation 1.416	-3.82 Score on a scale Standard Deviation 1.306	-4.14 Score on a scale Standard Deviation 1.344

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. For patients who received escape therapy, withdrew prematurely or where the DAS28 score was missing the response was set to 'No response'.

The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline \< -1.2. EULAR Moderate response: DAS28 \>3.2 to ≤ 5.1 or a change from Baseline \< -0.6 to ≥ -1.2.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 24 Good EULAR Response	5.9 Percentage of participants	24.6 Percentage of participants	40.7 Percentage of participants
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 24 Moderate EULAR Response	28.8 Percentage of participants	39.6 Percentage of participants	33.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm) \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline \< -1.2. EULAR Moderate response: DAS28 \>3.2 to ≤ 5.1 or a change from Baseline \< -0.6 to ≥ -1.2.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 52 Good Response	7.1 Percentage of participants	27.6 Percentage of participants	44.0 Percentage of participants
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 52 Moderate Response	22.1 Percentage of participants	30.3 Percentage of participants	24.1 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: ITT population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation was used for missing ESR and VAS assessments. For patients who received escape therapy, withdrew prematurely or where the DAS28 score was missing the response was set to 'No response'.

The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm) \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline \< -1.2. EULAR Moderate response: DAS28 \>3.2 to ≤ 5.1 or a change from Baseline \< -0.6 to ≥ -1.2.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 104 Good Response	23.4 Percentage of participants	39.6 Percentage of participants	45.7 Percentage of participants
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 104 Moderate Response	9.7 Percentage of participants	15.8 Percentage of participants	13.1 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 remission is defined as a DAS28 score \<2.6.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=212 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=304 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=315 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With DAS28 Remission at Week 24	3.8 Percentage of participants	17.8 Percentage of participants	33.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=156 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=249 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=275 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With DAS28 Remission at Week 52	7.7 Percentage of participants	30.5 Percentage of participants	48.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 104

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=136 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=224 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=241 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With DAS28 Remission at Week 104	52.9 Percentage of participants	55.4 Percentage of participants	64.7 Percentage of participants

SECONDARY outcome

Timeframe: 24 Weeks

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=208 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=301 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=311 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 24	895.85 Score on a scale*week Standard Deviation 179.465	767.02 Score on a scale*week Standard Deviation 208.462	670.45 Score on a scale*week Standard Deviation 193.506

SECONDARY outcome

Timeframe: 52 Weeks

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=146 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=230 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=265 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 52	1755.25 Score on a scale*week Standard Deviation 353.653	1423.12 Score on a scale*week Standard Deviation 415.188	1235.80 Score on a scale*week Standard Deviation 412.134

SECONDARY outcome

Timeframe: 104 Weeks

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis. LOCF was used for tender and swollen joint counts, no imputation used for missing ESR and VAS assessments. All assessments were set to missing from the time a patient received escape therapy.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=134 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=223 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=238 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 104	2793.01 Score on a scale*week Standard Deviation 675.840	2426.11 Score on a scale*week Standard Deviation 743.882	2094.71 Score on a scale*week Standard Deviation 749.148

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with Baseline and post-Baseline radiographic data available for this outcome measure. Data collected after withdraw or on escape therapy is excluded.

Radiographs were taken of each hand and foot at Baseline and Week 24 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=283 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=327 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=334 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Modified Total Sharp-Genant Score at Week 24	0.51 Score on a scale Standard Deviation 1.336	0.22 Score on a scale Standard Deviation 0.843	0.19 Score on a scale Standard Deviation 0.985

SECONDARY outcome

Timeframe: Baseline, Week 80

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Linear extrapolation was used to impute missing data. Data collected after withdraw or on escape therapy is excluded.

Radiographs were taken of each hand and foot at Baseline and Week 80 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=294 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=343 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=353 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Modified Total Sharp-Genant Score at Week 80	1.60 Score on a scale Standard Deviation 4.658	0.46 Score on a scale Standard Deviation 1.845	0.31 Score on a scale Standard Deviation 1.273

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Data was set to missing for patients who withdrew or received escape therapy.

Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=283 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=327 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=334 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Erosion Score at Week 24	0.36 Score on a scale Standard Deviation 0.928	0.15 Score on a scale Standard Deviation 0.563	0.11 Score on a scale Standard Deviation 0.625

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data for this outcome measure. Missing Week 52 data was imputed using Linear extrapolation. Data was set to missing for patients who withdrew or received escape therapy.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=290 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=339 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=348 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Erosion Score at Week 52	0.71 Score on a scale Standard Deviation 1.892	0.21 Score on a scale Standard Deviation 0.920	0.17 Score on a scale Standard Deviation 0.860

SECONDARY outcome

Timeframe: Baseline, Week 80

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Linear extrapolation was used to impute missing data. Data collected after withdraw or on escape therapy is excluded.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=294 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=343 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=353 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Erosion Score at Week 80	1.01 Score on a scale Standard Deviation 3.101	0.27 Score on a scale Standard Deviation 1.101	0.18 Score on a scale Standard Deviation 1.060

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Linear extrapolation was used to impute missing data. Data collected after withdraw or on escape therapy is excluded.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=294 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=343 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=353 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Erosion Score at Week 104	1.24 Score on a scale Standard Deviation 3.947	0.34 Score on a scale Standard Deviation 1.337	0.22 Score on a scale Standard Deviation 1.301

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Data was set to missing for patients who withdrew or received escape therapy.

Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower change from Baseline indicated a better score.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=283 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=327 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=334 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Joint Space Narrowing Score at Week 24	0.15 Score on a scale Standard Deviation 0.659	0.07 Score on a scale Standard Deviation 0.416	0.08 Score on a scale Standard Deviation 0.468

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdraw or on escape therapy was excluded.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=290 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=339 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=348 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Joint Space Narrowing Score at Week 52	0.42 Score on a scale Standard Deviation 1.695	0.13 Score on a scale Standard Deviation 0.739	0.12 Score on a scale Standard Deviation 0.640

SECONDARY outcome

Timeframe: Baseline, Week 80

Population: Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdraw or on escape therapy was excluded.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=294 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=343 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=353 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Joint Space Narrowing Score at Week 80	0.59 Score on a scale Standard Deviation 2.589	0.19 Score on a scale Standard Deviation 1.035	0.13 Score on a scale Standard Deviation 0.626

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdraw or on escape therapy was excluded.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=294 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=343 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=353 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Joint Space Narrowing Score at Week 104	0.72 Score on a scale Standard Deviation 3.321	0.24 Score on a scale Standard Deviation 1.368	0.15 Score on a scale Standard Deviation 0.772

SECONDARY outcome

Timeframe: Baseline, Week 24

Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=283 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=327 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=334 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With no Progression of Erosion at Week 24	73.9 Percentage of participants	83.8 Percentage of participants	88.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdraw or on escape therapy was excluded.

Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=290 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=339 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=348 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With no Progression of Erosion at Week 52	70.0 Percentage of participants	82.6 Percentage of participants	86.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdrawal or on escape therapy was excluded.

Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=294 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=343 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=353 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With no Progression of Erosion at Week 104	71.1 Percentage of participants	78.4 Percentage of participants	85.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score was defined as a change from Baseline of less than or equal to zero.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=283 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=327 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=334 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With no Progression of Joint Space Narrowing at Week 24	88.3 Percentage of participants	91.4 Percentage of participants	91.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdrawal or on escape therapy was excluded.

Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score is defined as a change from Baseline of less than or equal to zero.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=290 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=339 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=348 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With no Progression of Joint Space Narrowing at Week 52	84.5 Percentage of participants	90.6 Percentage of participants	90.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline and post-Baseline radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation. Data collected after withdrawal or on escape therapy was excluded.

Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score is defined as a change from Baseline of less than or equal to zero.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=294 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=343 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=353 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants With no Progression of Joint Space Narrowing at Week 104	80.3 Percentage of participants	86.0 Percentage of participants	91.2 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population (all participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=146 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=235 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=263 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in HAQ Disability Index (HAQ-DI) at Week 52	-0.39 Score on a scale Standard Deviation 0.570	-0.52 Score on a scale Standard Deviation 0.607	-0.58 Score on a scale Standard Deviation 0.583

SECONDARY outcome

Timeframe: Baseline, Week 104

HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8). Total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=127 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=218 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=231 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in HAQ Disability Index at Week 104	-0.50 Score on a scale Standard Deviation 0.612	-0.58 Score on a scale Standard Deviation 0.608	-0.61 Score on a scale Standard Deviation 0.661

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population (all participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. . Data was set to missing for patients who received escape therapy.

The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=203 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=283 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=294 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Quality Life Short Form-36 (SF-36) Score at Week 24 Physical component score	5.54 Score on a scale Standard Deviation 8.459	8.15 Score on a scale Standard Deviation 8.135	8.46 Score on a scale Standard Deviation 8.520
Change From Baseline in Quality Life Short Form-36 (SF-36) Score at Week 24 Mental component score	3.27 Score on a scale Standard Deviation 11.092	4.63 Score on a scale Standard Deviation 11.702	5.17 Score on a scale Standard Deviation 10.869

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population (all participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. Data was set to missing for patients who received escape therapy.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=144 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=230 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=261 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in SF-36 Score at Week 52 Physical component summary score	5.6 Score on a scale Standard Deviation 8.42	9.2 Score on a scale Standard Deviation 8.29	10.0 Score on a scale Standard Deviation 9.13
Change From Baseline in SF-36 Score at Week 52 Mental component summary score	3.7 Score on a scale Standard Deviation 10.67	5.6 Score on a scale Standard Deviation 11.94	5.5 Score on a scale Standard Deviation 11.49

SECONDARY outcome

Timeframe: Baseline, Week 104

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=130 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=211 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=228 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in SF-36 Score at Week 104 Physical component score	8.7 Score on a scale Standard Deviation 9.53	10.1 Score on a scale Standard Deviation 9.50	9.8 Score on a scale Standard Deviation 9.66
Change From Baseline in SF-36 Score at Week 104 Mental component score	5.2 Score on a scale Standard Deviation 10.27	5.7 Score on a scale Standard Deviation 11.22	6.2 Score on a scale Standard Deviation 11.55

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing FACIT-Fatigue scores. All assessments were set to missing from the time a patient received escape therapy.

FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=214 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=307 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=313 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score at Week 24	5.32 Score on a scale Standard Deviation 10.133	7.14 Score on a scale Standard Deviation 10.145	6.91 Score on a scale Standard Deviation 8.877

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=157 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=250 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=276 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in FACIT-F Score at Week 52	5.57 Score on a scale Standard Deviation 10.087	8.14 Score on a scale Standard Deviation 10.880	8.27 Score on a scale Standard Deviation 9.387

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with data available for analysis. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=138 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=224 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=244 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in FACIT-F Score at Week 104	6.62 Score on a scale Standard Deviation 9.544	7.85 Score on a scale Standard Deviation 10.578	8.63 Score on a scale Standard Deviation 9.737

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) with positive RF at Baseline. No imputation was used for missing data. All assessments were set to missing from the time a patient received escape therapy.

Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 24 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= \>15 IU/mL. A lower number change from Baseline indicated a better result.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=179 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=252 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=268 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Rheumatoid Factor (RF) at Week 24 in Those Patients With Positive RF	-44.7 IU/mL Standard Deviation 273.71	-79.3 IU/mL Standard Deviation 315.06	-75.6 IU/mL Standard Deviation 205.76

SECONDARY outcome

Timeframe: Baseline, Week 52

Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 52 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= \>15 IU/mL. A lower number change from Baseline indicated a better result.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=132 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=208 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=232 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Rheumatoid Factor (RF) at Week 52 in Those Patients With Positive RF	-21.5 IU/mL Standard Deviation 444.37	8.6 IU/mL Standard Deviation 575.02	-71.6 IU/mL Standard Deviation 213.45

SECONDARY outcome

Timeframe: Baseline, Week 104

Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 104 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= \>15 IU/mL. A lower number change from Baseline indicated a better result.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=115 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=191 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=206 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Change From Baseline in Rheumatoid Factor (RF) at Week 104 in Those Patients With Positive RF	-29.0 IU/mL Standard Deviation 304.46	-25.1 IU/mL Standard Deviation 431.29	-39.2 IU/mL Standard Deviation 253.29

SECONDARY outcome

Timeframe: 6 months

Population: Participants from the ITT population \[N=393,399,398\] (all randomized participants who received study drug) with ACR20 response. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who withdrew, received escape therapy or who did not achieve a response were censored.

Time in days until ACR20 response. ACR20 response was defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=209 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=299 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=328 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Time to Onset of ACR20 by Treatment Group	116.0 Days Interval 113.0 to 141.0	57.0 Days Interval 57.0 to 82.0	57.0 Days Interval 56.0 to 57.0

SECONDARY outcome

Timeframe: 6 months

Population: Participants from the ITT population \[N=393,399,398\] (all randomized participants who received study drug) with ACR50 response. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who withdrew, received escape therapy or who did not achieve a response were censored.

Time in days until ACR50 response. ACR50 response was defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=76 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=178 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=205 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Time to Onset of ACR50 by Treatment Group	NA Days Interval 173.0 to Value not calculable due to insufficient events.	170.0 Days Interval 169.0 to Value not calculable due to insufficient events.	141.0 Days Interval 139.0 to 169.0

SECONDARY outcome

Timeframe: 6 months

Population: Participants from the ITT population \[N=393,399,398\] (all randomized participants who received study drug) with ACR70 response. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who withdrew, received escape therapy or who did not achieve a response were censored.

Time in days until ACR70 response. ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=23 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=89 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=95 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Time to Onset of ACR70 by Treatment Group	NA Days Value not calculable due to insufficient events.	NA Days Interval 176.0 to Value not calculable due to insufficient events.	NA Days Value not calculable due to insufficient events.

SECONDARY outcome

Timeframe: 104 Weeks

Population: Intent-to-treat population included all randomized participants who received at least 1 dose of study drug. Data on escape therapy is excluded.

Insufficient therapeutic response (patient not responding to the drug as assessed by the physician) was selected by the investigator as a reason that the patient withdrew from the study.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants Who Withdraw Due to Lack of Sufficient Therapeutic Response	3.1 Percentage of participants	0.3 Percentage of participants	0.5 Percentage of participants

SECONDARY outcome

Timeframe: 104 Weeks

Population: Participants from the Intent-to-treat population (all randomized participants who received study drug) with data available for analysis.

In Escape 1, participants in the Tocilizumab 4 mg/kg + Methotrexate and Tocilizumab 8 mg/kg + Methotrexate groups received tocilizumab 8 mg/kg as escape therapy. Participants in the Placebo + Methotrexate group received tocilizumab 4 mg/kg as escape therapy. In Escape 2, all participants received tocilizumab 8 mg/kg.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=392 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants in Each Treatment Group Who Receive Escape Therapy Escape 1 Therapy	50 Percentage of participants	24 Percentage of participants	15 Percentage of participants
Percentage of Participants in Each Treatment Group Who Receive Escape Therapy Escape 2 Therapy	8 Percentage of participants	2 Percentage of participants	3 Percentage of participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for morning stiffness, FACIT-Fatigue score, ESR and VAS assessment. Patients with missing data, early withdrawal or who received escape therapy were set to 'Non Responder'.

The percentage of participants, who achieved ACR remission at any study visit up to Week 24. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness \< 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR \< 30 mm/hr for a female or 20 mm/hr for a male.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 24	0.0 Percentage of participants	0.3 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: 52 Weeks

Population: Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for morning stiffness, FACIT-Fatigue score, ESR and VAS assessment. Patients with missing data, early withdrawal or who received escape therapy were set to 'Non Responder'.

The percentage of participants, who achieved ACR remission at any study visit up to Week 52. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness \< 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR \< 30 mm/hr for a female or 20 mm/hr for a male.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 52	0.0 Percentage of participants	1.8 Percentage of participants	1.5 Percentage of participants

SECONDARY outcome

Timeframe: 104 Weeks

Population: Intent-to-treat population included all randomized participants who received study drug. LOCF was used for tender and swollen joint counts, no imputation used for morning stiffness, FACIT-Fatigue score, ESR and VAS assessment. Patients with missing data, early withdrawal or who received escape therapy were set to 'Non Responder'.

The percentage of participants who achieved ACR remission at any study visit up to Week 104. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness \< 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR \< 30 mm/hr for a female or 20 mm/hr for a male.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 104	0.0 Percentage of participants	2.0 Percentage of participants	2.5 Percentage of participants

SECONDARY outcome

Timeframe: 52 Weeks

Population: Intent-to-treat population included all randomized participants who received at least 1 dose of study drug. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments. Patients who received escape therapy, withdrew or where an ACR could not be calculated, were set to 'Non Responder'.

Complete clinical response is defined as a continuous 6-month period of remission by ACR criteria \[defined as five of the following criteria are met for at least two consecutive months: morning stiffness \< 15 minutes, no fatigue, no joint pain, no joint tenderness or swelling, and ESR \< 30 mm/hr for a female or 20 mm/hr for a male\] and no radiographic progression \[defined as change from baseline ≤ 0 in the total Sharp-Genant score, erosion score, and JSN score\]. Patients who achieve a complete clinical response at any time in the study are counted as responders, even if the response is not maintained.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants Who Achieved Complete Clinical Response at Week 52	0.0 Percentage of participants	0.3 Percentage of participants	0.5 Percentage of participants

SECONDARY outcome

Timeframe: 104 Weeks

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=393 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=399 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate n=398 Participants Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Percentage of Participants Who Achieved Complete Clinical Response at Week 104	0 Percentage of participants	0.3 Percentage of participants	1.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 260

Population: Participants from the Modified Intent-to-treatment population, all exposure group, with data available at Baseline and Week 260. LOCF was used for tender and swollen joint counts, no imputation used for missing HAQ Score, CRP, ESR and VAS assessments.

ACR20/50/70/90 response is defined as a ≥ 20/50/70/90% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=473 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Percentage of Participants With ACR Response at Week 260 ACR 20 Response	82.9 Percentage of participants	—	—
End of Study: Percentage of Participants With ACR Response at Week 260 ACR 50 Response	64.9 Percentage of participants	—	—
End of Study: Percentage of Participants With ACR Response at Week 260 ACR 70 Response	42.1 Percentage of participants	—	—
End of Study: Percentage of Participants With ACR Response at Week 260 ACR 90 Response	16.7 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Week 260

Population: Participants from the Modified Intent-to-treatment population, all exposure group, with data available at Week 260. Last observation carried forward was used for tender and swollen joint counts. No imputation used for ESR and Patients Global Assessment of Disease Activity VAS.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=458 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Percentage of Participants With DAS28 Remission at Week 260	59.4 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Week 260

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=458 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Percentage of Participants With DAS28 Low Disease Activity (LDA) at Week 260	73.8 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline, Week 260

The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. EULAR Good response: DAS28 ≤ 3.2 and a change from Baseline \< -1.2. EULAR Moderate response: DAS28 \>3.2 to ≤ 5.1 or a change from Baseline \< -0.6 to ≥ -1.2.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=455 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Percentage of Participants With DAS28 European League Against Rheumatism (EULAR) Good or Moderate Response at Week 260 Good Response	74.1 Percentage of participants	—	—
End of Study: Percentage of Participants With DAS28 European League Against Rheumatism (EULAR) Good or Moderate Response at Week 260 Moderate Response	24.0 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline, Week 260

Population: Participants from the Modified Intent-to-treat population, All Tocilizumab Exposure group, with data available at Baseline and Week 260. Last observation carried forward was used for missing joint counts.

66 joints were assessed at Baseline and Week 260 for swelling and joints are classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=480 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Change From Baseline in Swollen Joint Count at Week 260	-14.2 Joint Count Standard Deviation 10.34	—	—

SECONDARY outcome

Timeframe: Baseline, Week 260

68 joints were assessed at Baseline and Week 260 for tenderness and joints are classified as tender/not tender for a total possible swollen joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=480 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Change From Baseline in Tender Joint Count at Week 260	-23.6 Joint Count Standard Deviation 14.20	—	—

SECONDARY outcome

Timeframe: Baseline, Week 260

Population: Participants from the Modified Intent-to-treat population, All Tocilizumab Exposure group, with data available at Baseline and Week 260. No imputation was used for missing HAQ score.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=444 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 260	-0.58 Score on a scale Standard Deviation 0.657	—	—

SECONDARY outcome

Timeframe: Baseline, Week 260

Population: Participants from the Modified Intent-to-treat population, all tocilizumab exposure group, with data available at Baseline and Week 260. No imputation was used for missing VAS assessments.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=471 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Change From Baseline in the Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) at Week 260	-33.7 mm Standard Deviation 27.22	—	—

SECONDARY outcome

Timeframe: Baseline, Week 260

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=469 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Change From Baseline in the Physician's Global Assessment of Disease Activity VAS at Week 260	-48.7 mm Standard Deviation 21.70	—	—

SECONDARY outcome

Timeframe: Baseline, Week 260

The patient assessed their pain at Baseline and Week 260 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=471 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Change From Baseline in the Patient's Pain VAS at Week 260	-28.2 mm Standard Deviation 26.78	—	—

SECONDARY outcome

Timeframe: Baseline, Week 260

Population: Participants from the Modified Intent-to-treat population, All Tocilizumab Exposure group, with data available for analysis at Baseline and Week 260.

FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Clinically relevant improvement is defined as a ≥5 change from Baseline.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=473 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Percentage of Participants With Clinical Improvement in the FACIT-Fatigue Score at Week 260	64.1 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline, Week 260

Population: Participants from the Modified Intent-to-treat population, All Tocilizumab Exposure group, with data available for analysis at Baseline and Week 260.

The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. Clinically relevant improvement is defined as a ≥5 change from Baseline.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=442 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Percentage of Participants With Clinical Relevant Improvement in the SF-36 Score at Week 260 Mental Components Summary	43.7 Percentage of participants	—	—
End of Study: Percentage of Participants With Clinical Relevant Improvement in the SF-36 Score at Week 260 Physical Components summary	69.9 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline, Week 260

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline, Week 104 and post-Week 104 radiographic data available for this outcome measure. Linear extrapolation was used to impute missing data.

Radiographs were taken of each hand and foot at Baseline and Week 260 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint).The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score. The results were reported based on the treatment the patient was originally randomized to.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=258 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=545 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Change From Baseline in Total Sharp-Genant Score at Week 260	3.30 Score on a scale Standard Deviation 6.093	1.54 Score on a scale Standard Deviation 4.272	—

SECONDARY outcome

Timeframe: Baseline, Week 260

Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot and were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best ) to 142 (worst). A lower number change from Baseline indicated a better score.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=258 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=545 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Change From Baseline in Erosion Score at Week 260	1.95 Score on a scale Standard Deviation 3.640	0.83 Score on a scale Standard Deviation 2.657	—

SECONDARY outcome

Timeframe: Baseline, Week 260

Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug, with Baseline, Week 104 and post-Week 104 radiographic data available for this outcome measure. Missing data was imputed using linear extrapolation.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=258 Participants Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.	Tocilizumab 4 mg/kg + Methotrexate n=545 Participants Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.	Tocilizumab 8 mg/kg + Methotrexate Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
End of Study: Change From Baseline in Joint Space Narrowing Score at Week 260	1.35 Score on a scale Standard Deviation 3.134	0.71 Score on a scale Standard Deviation 2.222	—

Adverse Events

Placebo + Methotrexate

Serious events: 26 serious events

Other events: 169 other events

Deaths: 0 deaths

All Tocilizumab 4 mg/kg + Methotrexate

Serious events: 58 serious events

Other events: 303 other events

Deaths: 0 deaths

All Tocilizumab 8 mg/kg + Methotrexate

Serious events: 267 serious events

Other events: 835 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER