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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)

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ClinicalTrials.gov Identifier: NCT00106535
Recruitment Status : Completed
First Posted : March 28, 2005
Results First Posted : June 7, 2011
Last Update Posted : February 6, 2014
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: tocilizumab [RoActemra/Actemra]
Drug: Placebo
Drug: Methotrexate
Enrollment 1196
Recruitment Details  
Pre-assignment Details This study was divided into two phases: a 2-year core placebo controlled treatment phase and an optional 3-year extension phase.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate All Tocilizumab Exposure + MTX
Hide Arm/Group Description 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 (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 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 (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.
Period Title: 2-year Placebo Controlled Period
Started 394 401 401 0
Intent-to-treat: Received Study Drug 393 399 398 0
Safety: Actual Treatment Received 392 399 399 0
Completed Week 24 356 373 366 0
Completed Week 52 326 342 338 0
Completed 287 [1] 309 [2] 310 [3] 0
Not Completed 107 92 91 0
[1]
Completed Week 104 (Year 2). 284 participants randomized to the Placebo arm entered the LTE period.
[2]
Completed Week 104. 304 participants randomized to the TCZ 4 mg/kg arm entered the LTE period.
[3]
Completed Week 104. 306 participants randomized to the TCZ 8 mg/kg arm entered the LTE period.
Period Title: Long-term Extension Period (Year 3 to 5)
Started 0 0 0 894 [1]
Completed 0 0 0 704 [2]
Not Completed 0 0 0 190
[1]
Entered the Long-term Extension.
[2]
Completed the study.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate Total
Hide Arm/Group Description Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly. Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly. Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly. Total of all reporting groups
Overall Number of Baseline Participants 393 399 398 1190
Hide Baseline Analysis Population Description
Baseline measures are based on the Intent-to-treat population that included all randomized participants who received study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 393 participants 399 participants 398 participants 1190 participants
51.3  (12.41) 51.4  (12.59) 53.4  (11.72) 52.0  (12.24)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 393 participants 399 participants 398 participants 1190 participants
Female
328
  83.5%
336
  84.2%
325
  81.7%
989
  83.1%
Male
65
  16.5%
63
  15.8%
73
  18.3%
201
  16.9%
1.Primary Outcome
Title Percentage of Participants With American College of Rheumatology-ACR20 Response
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
27.0 50.6 56.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Modified Total Sharp-Genant Score at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 290 339 348
Mean (Standard Deviation)
Unit of Measure: Score on a scale
1.13  (2.962) 0.34  (1.451) 0.29  (1.282)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Van Elteren's test
Comments Stratified by region.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Van Elteren's test
Comments Stratified by region.
3.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 366 376 374
Least Squares Mean (Full Range)
Unit of Measure: Score on a scale*week
-58.11
(-699.8 to 401.0)
-128.37
(-1059.6 to 266.8)
-144.06
(-895.7 to 323.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments Adjusted for region and original treatment group.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -70.26
Confidence Interval (2-Sided) 95%
-96.96 to -43.56
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments Adjusted for region and original treatment group.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -85.95
Confidence Interval (2-Sided) 95%
-112.69 to -59.22
Estimation Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in the Modified Total Sharp-Genant Score at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 294 343 353
Mean (Standard Deviation)
Unit of Measure: Score on a scale
1.96  (5.956) 0.58  (2.357) 0.37  (1.547)
5.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 366 376 374
Least Squares Mean (Full Range)
Unit of Measure: Score on a scale*week
-139.40
(-1503.9 to 801.9)
-287.50
(-2145.6 to 630.8)
-320.80
(-1776.6 to 677.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments Adjusted for region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -148.10
Confidence Interval (2-Sided) 95%
-205.22 to -90.98
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments Adjusted for region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -181.40
Confidence Interval (2-Sided) 95%
-238.60 to -124.21
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With ACR50 Response
Hide Description 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].
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
9.7 25.1 32.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With ACR70 Response
Hide Description 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].
Time Frame Baseline,Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
2.0 11.0 12.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
8.Secondary Outcome
Title Swollen Joint Count (66 Joint Count): Mean Change From Baseline at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Mean (Standard Deviation)
Unit of Measure: joint count
Baseline Swollen Joint Count (SJC) 16.6  (9.23) 17.0  (9.78) 17.3  (9.48)
Change from Baseline at Week 24 (n=391,399, 397) -2.9  (10.37) -7.9  (9.31) -9.0  (9.76)
9.Secondary Outcome
Title Tender Joint Count (68 Joint Count): Mean Change From Baseline at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Mean (Standard Deviation)
Unit of Measure: joint count
Baseline Tender Joint Count (TJC) 27.9  (14.80) 27.9  (14.15) 29.3  (15.22)
Change from Baseline at Week 24 (n=391,399, 397) -4.8  (14.61) -12.2  (14.94) -14.2  (14.58)
10.Secondary Outcome
Title Patient's Global Visual Analog Scale (VAS): Mean Change From Baseline at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Mean (Standard Deviation)
Unit of Measure: millimeters (mm)
Baseline Patient Visual Analog Scale (VAS) 63.1  (23.36) 61.0  (23.25) 62.7  (22.49)
Change from Baseline at Week 24 (n=213,308,316) -17.5  (26.60) -25.2  (27.09) -25.2  (24.95)
11.Secondary Outcome
Title Physician's Global VAS: Mean Change From Baseline at Week 24
Hide Description 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).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Mean (Standard Deviation)
Unit of Measure: mm
Baseline Physician's Visual Analog Scale (VAS) 63.1  (17.34) 62.3  (16.8) 62.7  (16.90)
Change from Baseline at Week 24 (n=214,307,320) -29.0  (24.35) -36.1  (24.31) -39.8  (21.82)
12.Secondary Outcome
Title Patient's Pain VAS: Mean Change From Baseline at Week 24
Hide Description 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.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Mean (Standard Deviation)
Unit of Measure: mm
Baseline Patient Pain Visual Analog Scale (VAS) 55.3  (22.07) 53.3  (21.97) 55.7  (22.34)
Change from Baseline at Week 24 (n=213,308,317) -12.5  (24.92) -19.5  (25.24) -21.8  (25.93)
13.Secondary Outcome
Title C-Reactive Protein (CRP): Mean Change From Baseline at Week 24
Hide Description The serum concentration of C-Reactive Protein (CRP) is measured in mg/dL. A reduction in the level is considered an improvement.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Mean (Standard Deviation)
Unit of Measure: milligrams/deciliter (mg/dL)
Baseline C-Reactive Protein (CRP) 2.235  (2.5068) 2.076  (2.3892) 2.337  (2.6065)
Change from Baseline at Week 24 (n=214,308,321) -0.3560  (2.12778) -0.9558  (2.35222) -2.0699  (2.50035)
14.Secondary Outcome
Title Erythrocyte Sedimentation Rate: Mean Change From Baseline at Week 24
Hide Description The Erythrocyte Sedimentation Rate (ESR) was measured in mm/hr. A reduction in the level is considered an improvement.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Mean (Standard Deviation)
Unit of Measure: millimeters/hour (mm/hr)
Baseline Erythrocyte Sedimentation Rate (ESR) 46.5  (24.69) 45.9  (25.12) 46.4  (24.8)
Change from Baseline at Week 24 (n=211,304,318) -9.5  (24.01) -21.8  (23.71) -36.8  (24.12)
15.Secondary Outcome
Title Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline HAQ-DI 1.5  (0.62) 1.5  (0.64) 1.5  (0.60)
Change from Baseline at Week 24 (n=197,292,301) -0.32  (0.516) -0.45  (0.531) -0.51  (0.580)
16.Secondary Outcome
Title Percentage of Participants With American College of Rheumatology (ACR20) Response at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
24.7 47.9 55.8
17.Secondary Outcome
Title Percentage of Participants With ACR20 Response at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
29.3 49.1 54.5
18.Secondary Outcome
Title Percentage of Participants With ACR50 Response at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
10.2 30.3 36.4
19.Secondary Outcome
Title Percentage of Participants With ACR50 Response at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
19.8 37.6 38.9
20.Secondary Outcome
Title Percentage of Participants With ACR70 Response at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
3.8 16.5 20.1
21.Secondary Outcome
Title Percentage of Participants With ACR70 Response at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
12.2 24.3 22.4
22.Secondary Outcome
Title Percentage of Participants With ACR70 Response Maintained for 6 Consecutive Months
Hide Description 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.
Time Frame 104 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
5.6 11.5 14.3
23.Secondary Outcome
Title Change From Baseline in Swollen Joint Count at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 391 399 397
Mean (Standard Deviation)
Unit of Measure: Joint count
-2.5  (11.07) -8.0  (9.95) -10.2  (10.65)
24.Secondary Outcome
Title Change From Baseline in Tender Joint Count at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 391 399 397
Mean (Standard Deviation)
Unit of Measure: Joint count
-4.1  (15.53) -12.3  (15.74) -15.6  (16.04)
25.Secondary Outcome
Title Change From Baseline in Patient's Global Assessment of Disease Activity at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 156 248 281
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-21.1  (26.22) -27.2  (28.83) -29.8  (25.61)
26.Secondary Outcome
Title Change From Baseline in Physicians Global Assessment of Disease Activity at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 after the patient received escape therapy.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 155 246 279
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-35.2  (25.13) -42.2  (23.57) -45.4  (22.22)
27.Secondary Outcome
Title Change From Baseline in the Patient's Pain VAS at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 156 248 282
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-15.0  (25.10) -22.9  (25.70) -26.1  (25.51)
28.Secondary Outcome
Title Change From Baseline in C-Reactive Protein (CRP) at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 157 247 282
Mean (Standard Deviation)
Unit of Measure: mg/dL
-0.3800  (2.50681) -1.0615  (2.39897) -2.2584  (2.71950)
29.Secondary Outcome
Title Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 149 235 274
Mean (Standard Deviation)
Unit of Measure: mm/hr
-10.9  (24.27) -25.6  (24.68) -38.5  (24.31)
30.Secondary Outcome
Title Change From Baseline in Swollen Joint Count at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 391 399 397
Mean (Standard Deviation)
Unit of Measure: Joint count
-3.5  (11.65) -9.0  (10.76) -11.3  (11.31)
31.Secondary Outcome
Title Change From Baseline in Tender Joint Count at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 391 399 397
Mean (Standard Deviation)
Unit of Measure: Joint count
-5.9  (17.07) -13.6  (16.53) -17.7  (16.73)
32.Secondary Outcome
Title Change From Baseline in Patient's Global Assessment of Disease Activity at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 137 228 248
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-33.2  (26.35) -31.6  (27.05) -33.9  (26.60)
33.Secondary Outcome
Title Change From Baseline in Physicians Global Assessment of Disease Activity at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 139 229 250
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-43.9  (21.55) -49.1  (20.33) -48.7  (22.20)
34.Secondary Outcome
Title Change From Baseline in the Patient's Pain VAS at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 137 228 248
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-25.6  (24.44) -26.6  (25.39) -28.9  (25.47)
35.Secondary Outcome
Title Change From Baseline in C-Reactive Protein (CRP) at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 139 231 251
Mean (Standard Deviation)
Unit of Measure: mg/dL
-1.6346  (2.28001) -1.6863  (2.20965) -2.3068  (2.65256)
36.Secondary Outcome
Title Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 139 231 247
Mean (Standard Deviation)
Unit of Measure: mm/hr
-30.7  (22.26) -35.4  (25.07) -36.9  (23.39)
37.Secondary Outcome
Title Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 52
Hide Description 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).
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 146 235 263
Measure Type: Number
Unit of Measure: Percentage of participants
52.7 59.6 62.7
38.Secondary Outcome
Title Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 104
Hide Description

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).

.

Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 127 218 231
Measure Type: Number
Unit of Measure: Percentage of participants
58.3 63.3 62.3
39.Secondary Outcome
Title Area Under Curve (AUC) of the ACRn to Week 24
Hide Description 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.
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 216 308 320
Mean (Standard Deviation)
Unit of Measure: Score on a scale*week
609.11  (5551.669) 2791.49  (5479.514) 3528.89  (5812.582)
40.Secondary Outcome
Title Area Under Curve (AUC) of the ACRn to Week 52
Hide Description 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.
Time Frame 52 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 156 247 279
Least Squares Mean (Full Range)
Unit of Measure: Score on a scale*week
5551.25
(-49420.8 to 25818.8)
10763.54
(-74637.5 to 33589.0)
12644.01
(-13773.8 to 31246.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments Adjusted for region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5212.28
Confidence Interval (2-Sided) 95%
3139.40 to 7285.16
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Adjusted for region.
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7092.76
Confidence Interval (2-Sided) 95%
5066.16 to 9119.36
Estimation Comments [Not Specified]
41.Secondary Outcome
Title Area Under Curve (AUC) of the ACRn Score at Week 104
Hide Description 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.
Time Frame 104 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 138 228 249
Mean (Standard Deviation)
Unit of Measure: Score on a scale*week
21094.97  (22341.489) 27141.08  (24296.659) 30876.59  (18177.420)
42.Secondary Outcome
Title Change From Baseline in Disease Activity Score (DAS28) at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 208 301 311
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-1.49  (1.257) -2.45  (1.401) -3.28  (1.383)
43.Secondary Outcome
Title Change From Baseline in Disease Activity Score (DAS28) at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 153 247 273
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-1.88  (1.319) -2.97  (1.391) -3.80  (1.263)
44.Secondary Outcome
Title Change From Baseline in Disease Activity Score (DAS28) at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 134 223 238
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-3.70  (1.416) -3.82  (1.306) -4.14  (1.344)
45.Secondary Outcome
Title Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 24
Hide Description

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.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
Good EULAR Response 5.9 24.6 40.7
Moderate EULAR Response 28.8 39.6 33.7
46.Secondary Outcome
Title Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 52
Hide Description

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.

Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
Good Response 7.1 27.6 44.0
Moderate Response 22.1 30.3 24.1
47.Secondary Outcome
Title Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 104
Hide Description

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.

Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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'.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 393 399 398
Measure Type: Number
Unit of Measure: Percentage of participants
Good Response 23.4 39.6 45.7
Moderate Response 9.7 15.8 13.1
48.Secondary Outcome
Title Percentage of Participants With DAS28 Remission at Week 24
Hide Description 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.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 212 304 315
Measure Type: Number
Unit of Measure: Percentage of participants
3.8 17.8 33.3
49.Secondary Outcome
Title Percentage of Participants With DAS28 Remission at Week 52
Hide Description 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.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 156 249 275
Measure Type: Number
Unit of Measure: Percentage of participants
7.7 30.5 48.0
50.Secondary Outcome
Title Percentage of Participants With DAS28 Remission at Week 104
Hide Description 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.
Time Frame Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 136 224 241
Measure Type: Number
Unit of Measure: Percentage of participants
52.9 55.4 64.7
51.Secondary Outcome
Title Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 24
Hide Description 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. Higher calculated AUC values are worse (indicate higher disease activity).
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 208 301 311
Mean (Standard Deviation)
Unit of Measure: Score on a scale*week
895.85  (179.465) 767.02  (208.462) 670.45  (193.506)
52.Secondary Outcome
Title Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 52
Hide Description 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. Higher calculated AUC values are worse (indicate higher disease activity).
Time Frame 52 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 146 230 265
Mean (Standard Deviation)
Unit of Measure: Score on a scale*week
1755.25  (353.653) 1423.12  (415.188) 1235.80  (412.134)
53.Secondary Outcome
Title Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 104
Hide Description 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. Higher calculated AUC values are worse (indicate higher disease activity).
Time Frame 104 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 134 223 238
Mean (Standard Deviation)
Unit of Measure: Score on a scale*week
2793.01  (675.840) 2426.11  (743.882) 2094.71  (749.148)
54.Secondary Outcome
Title Change From Baseline in Modified Total Sharp-Genant Score at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 283 327 334
Mean (Standard Deviation)
Unit of Measure: Score on a scale
0.51  (1.336) 0.22  (0.843) 0.19  (0.985)
55.Secondary Outcome
Title Change From Baseline in Modified Total Sharp-Genant Score at Week 80
Hide Description 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.
Time Frame Baseline, Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 294 343 353
Mean (Standard Deviation)
Unit of Measure: Score on a scale
1.60  (4.658) 0.46  (1.845) 0.31  (1.273)
56.Secondary Outcome
Title Change From Baseline in Erosion Score at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 283 327 334
Mean (Standard Deviation)
Unit of Measure: Score on a scale
0.36  (0.928) 0.15  (0.563) 0.11  (0.625)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0023
Comments [Not Specified]
Method Van Elteren's test
Comments Stratified by region.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Van Elteren's test
Comments [Not Specified]
57.Secondary Outcome
Title Change From Baseline in Erosion Score at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 290 339 348
Mean (Standard Deviation)
Unit of Measure: Score on a scale
0.71  (1.892) 0.21  (0.920) 0.17  (0.860)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 4 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Van Elteren's test
Comments Stratified by region.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate, Tocilizumab 8 mg/kg + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Van Elteren's test
Comments Stratified by region.
58.Secondary Outcome
Title Change From Baseline in Erosion Score at Week 80
Hide Description 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.
Time Frame Baseline, Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 294 343 353
Mean (Standard Deviation)
Unit of Measure: Score on a scale
1.01  (3.101) 0.27  (1.101) 0.18  (1.060)
59.Secondary Outcome
Title Change From Baseline in Erosion Score at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 294 343 353
Mean (Standard Deviation)
Unit of Measure: Score on a scale
1.24  (3.947) 0.34  (1.337) 0.22  (1.301)
60.Secondary Outcome
Title Change From Baseline in Joint Space Narrowing Score at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 283 327 334
Mean (Standard Deviation)
Unit of Measure: Score on a scale
0.15  (0.659) 0.07  (0.416) 0.08  (0.468)
61.Secondary Outcome
Title Change From Baseline in Joint Space Narrowing Score at Week 52
Hide Description 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 number change from Baseline indicated a better score.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 290 339 348
Mean (Standard Deviation)
Unit of Measure: Score on a scale
0.42  (1.695) 0.13  (0.739) 0.12  (0.640)
62.Secondary Outcome
Title Change From Baseline in Joint Space Narrowing Score at Week 80
Hide Description 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 number change from Baseline indicated a better score.
Time Frame Baseline, Week 80
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 294 343 353
Mean (Standard Deviation)
Unit of Measure: Score on a scale
0.59  (2.589) 0.19  (1.035) 0.13  (0.626)
63.Secondary Outcome
Title Change From Baseline in Joint Space Narrowing Score at Week 104
Hide Description 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 number change from Baseline indicated a better score.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 294 343 353
Mean (Standard Deviation)
Unit of Measure: Score on a scale
0.72  (3.321) 0.24  (1.368) 0.15  (0.772)
64.Secondary Outcome
Title Percentage of Participants With no Progression of Erosion at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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 was excluded.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 283 327 334
Measure Type: Number
Unit of Measure: Percentage of participants
73.9 83.8 88.3
65.Secondary Outcome
Title Percentage of Participants With no Progression of Erosion at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 290 339 348
Measure Type: Number
Unit of Measure: Percentage of participants
70.0 82.6 86.8
66.Secondary Outcome
Title Percentage of Participants With no Progression of Erosion at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 294 343 353
Measure Type: Number
Unit of Measure: Percentage of participants
71.1 78.4 85.6
67.Secondary Outcome
Title Percentage of Participants With no Progression of Joint Space Narrowing at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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 on escape therapy was excluded.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 283 327 334
Measure Type: Number
Unit of Measure: Percentage of participants
88.3 91.4 91.9
68.Secondary Outcome
Title Percentage of Participants With no Progression of Joint Space Narrowing at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 290 339 348
Measure Type: Number
Unit of Measure: Percentage of participants
84.5 90.6 90.5
69.Secondary Outcome
Title Percentage of Participants With no Progression of Joint Space Narrowing at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 294 343 353
Measure Type: Number
Unit of Measure: Percentage of participants
80.3 86.0 91.2
70.Secondary Outcome
Title Change From Baseline in HAQ Disability Index (HAQ-DI) at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 146 235 263
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-0.39  (0.570) -0.52  (0.607) -0.58  (0.583)
71.Secondary Outcome
Title Change From Baseline in HAQ Disability Index at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 127 218 231
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-0.50  (0.612) -0.58  (0.608) -0.61  (0.661)
72.Secondary Outcome
Title Change From Baseline in Quality Life Short Form-36 (SF-36) Score at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 203 283 294
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Physical component score 5.54  (8.459) 8.15  (8.135) 8.46  (8.520)
Mental component score 3.27  (11.092) 4.63  (11.702) 5.17  (10.869)
73.Secondary Outcome
Title Change From Baseline in SF-36 Score at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 144 230 261
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Physical component summary score 5.6  (8.42) 9.2  (8.29) 10.0  (9.13)
Mental component summary score 3.7  (10.67) 5.6  (11.94) 5.5  (11.49)
74.Secondary Outcome
Title Change From Baseline in SF-36 Score at Week 104
Hide Description 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 indicated improvement.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 130 211 228
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Physical component score 8.7  (9.53) 10.1  (9.50) 9.8  (9.66)
Mental component score 5.2  (10.27) 5.7  (11.22) 6.2  (11.55)
75.Secondary Outcome
Title Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score at Week 24
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 214 307 313
Mean (Standard Deviation)
Unit of Measure: Score on a scale
5.32  (10.133) 7.14  (10.145) 6.91  (8.877)
76.Secondary Outcome
Title Change From Baseline in FACIT-F Score at Week 52
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 157 250 276
Mean (Standard Deviation)
Unit of Measure: Score on a scale
5.57  (10.087) 8.14  (10.880) 8.27  (9.387)
77.Secondary Outcome
Title Change From Baseline in FACIT-F Score at Week 104
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 138 224 244
Mean (Standard Deviation)
Unit of Measure: Score on a scale
6.62  (9.544) 7.85  (10.578) 8.63  (9.737)
78.Secondary Outcome
Title Change From Baseline in Rheumatoid Factor (RF) at Week 24 in Those Patients With Positive RF
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 179 252 268
Mean (Standard Deviation)
Unit of Measure: IU/mL
-44.7  (273.71) -79.3  (315.06) -75.6  (205.76)
79.Secondary Outcome
Title Change From Baseline in Rheumatoid Factor (RF) at Week 52 in Those Patients With Positive RF
Hide Description 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.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 132 208 232
Mean (Standard Deviation)
Unit of Measure: IU/mL
-21.5  (444.37) 8.6  (575.02) -71.6  (213.45)
80.Secondary Outcome
Title Change From Baseline in Rheumatoid Factor (RF) at Week 104 in Those Patients With Positive RF
Hide Description 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.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate Tocilizumab 4 mg/kg + Methotrexate Tocilizumab 8 mg/kg + Methotrexate
Hide Arm/Group Description:
Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly.
Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly.
Overall Number of Participants Analyzed 115 191 206
Mean (Standard Deviation)
Unit of Measure: IU/mL
-29.0  (304.46) -25.1  (431.29) -39.2  (253.29)
81.Secondary Outcome
Title Time to Onset of ACR20 by Treatment Group
Hide Description 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.