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Trial record 37 of 157 for:    Diseases | ( Map: Costa Rica )

A Study to Assess the Effect of Tocilizumab Plus Methotrexate on Safety and Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT00754572
Recruitment Status : Completed
First Posted : September 18, 2008
Results First Posted : May 15, 2015
Last Update Posted : May 15, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: tocilizumab [RoActemra/Actemra]
Drug: methotrexate
Enrollment 418
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tocilizumab
Hide Arm/Group Description Participants received tocilizumab 8 milligrams per kilogram (mg/kg) intravenously (iv), once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throuhgout the study.
Period Title: Overall Study
Started 418
Completed 347
Not Completed 71
Reason Not Completed
Adverse Event             19
Other             39
Protocol Violation             3
Withdrawal by Subject             3
Lack of Efficacy             2
Death             1
Administrative Reason             3
Lost to Follow-up             1
Arm/Group Title Tocilizumab
Hide Arm/Group Description Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Baseline Participants 418
Hide Baseline Analysis Population Description
Intention to treat (ITT) population: All participants who received at least one dose of study drug and who had at least one effectiveness measurement performed after baseline.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 418 participants
48.69  (12.36)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 418 participants
Female
371
  88.8%
Male
47
  11.2%
1.Primary Outcome
Title Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24
Hide Description

ACR50 is defined as 50 percent (%) improvement in: a) Swollen Joints Count (SJC) and Tender Joints Count (TJC) and b) Three of the following 5 assessments:

  1. Participant's global assessment of pain by Visual Analog Scale (VAS)
  2. Participant's global assessment of disease activity (VAS)
  3. Investigator/Physician's global assessment of disease activity (VAS)
  4. Participant's assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI)
  5. Acute phase reactant levels - Erythrocyte Sedimentation Rate or C-Reactive Protein (ESR or CRP)
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 381
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
73.23
(68.78 to 77.67)
2.Secondary Outcome
Title Percentage of Participants With ACR20 and ACR70 Response at Week 24
Hide Description

ACR20 and ACR70 are defined as 20 and 70 percent improvement respectively in: a) SJC and TJC and b) Three of the following 5 assessments:

  1. Participant's global assessment of pain by VAS
  2. Participant's global assessment of disease activity (VAS)
  3. Investigator/Physician's global assessment of disease activity (VAS)
  4. Participant's assessment of disability measured by HAQ-DI
  5. Acute phase reactant (ESR or CRP)
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 381
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
ACR 20
90.55
(87.61 to 93.49)
ACR 70
50.39
(45.37 to 55.41)
3.Secondary Outcome
Title Time to Onset of ACR20, ACR50, and ACR70
Hide Description

ACR20, ACR50 and ACR70 are defined as 20, 50 and 70 percent improvement respectively in: a) SJC and TJC and b) Three of the following 5 assessments:

  1. Participant's global assessment of pain by VAS
  2. Participant's global assessment of disease activity (VAS)
  3. Investigator/Physician's global assessment of disease activity (VAS)
  4. Participant's assessment of disability measured by HAQ-DI
  5. Acute phase reactant (ESR or CRP)
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not analyzed because of inconsistencies in the pooled data between countries.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Change From Baseline in Hemoglobin at Week 24
Hide Description [Not Specified]
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not analyzed because of inconsistencies in the pooled data between countries.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title SJC and TJC at Baseline and Week 24
Hide Description The number of swollen joints (66 joint count) were scored as swollen=1 and not swollen=0, and the number of tender joints (68 joint count ) were scored as tender=1 and not tender=0, and counted. Scores ranged from 0 to 66 for swollen joint counts and from 0 to 68 for tender joint counts. A positive change from baseline represents an improvement (a reduction in the number of swollen or tender joints).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 384
Mean (Standard Deviation)
Unit of Measure: joints
TJC-Baseline 25.06  (13.83)
TJC-Week 24 4.57  (7.57)
SJC-Baseline 16.09  (8.69)
SJC-Week 24 2.56  (4.26)
6.Secondary Outcome
Title Percent Change From Baseline in SJC and TJC at Week 24
Hide Description The number of swollen joints (66 joint count) were scored as swollen=1 and not swollen=0, and the number of tender joints (68 joint count ) were scored as tender=1 and not tender=0, and counted. Scores ranged from 0 to 66 for swollen joint counts and from 0 to 68 for tender joint counts. A positive change from baseline represents an improvement (a reduction in the number of swollen or tender joints).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 384
Mean (Standard Deviation)
Unit of Measure: percent change
TJC 81.2  (28.1)
SJC 84.8  (22.5)
7.Secondary Outcome
Title Pain as Assessed by the Participant at Baseline and Week 24
Hide Description The participants assessed their pain using a 0 to 100 millimeter (mm) 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". The participants marked the line corresponding to the level of their pain and the distance from the left edge was measured. A positive change from baseline represents an improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at the specified timepoints were included in the analysis. number (n) equals (=) number of participants analyzed for the given parameter at the specified time point.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 384
Mean (Standard Deviation)
Unit of Measure: mm
Baseline (n=384) 68.01  (20.39)
Week 24 (n=381) 22.94  (22.53)
8.Secondary Outcome
Title Percent Change From Baseline in Pain as Assessed by the Participant at Week 24
Hide Description The participants assessed their pain using a 0 to 100 millimeter (mm) 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". The participants marked the line corresponding to the level of their pain and the distance from the left edge was measured. A positive change from baseline represents an improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at Baseline and Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 381
Mean (Standard Deviation)
Unit of Measure: percent change
54.2  (177.0)
9.Secondary Outcome
Title Participant's Global Assessment of Disease Activity at Baseline and Week 24
Hide Description The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. 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 positive change from baseline represents an improvement (reduced level of disease activity).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. All participants with endpoint values collected at the specified timepoints were included in the analysis. n= number of participants analyzed for the given parameter at the specified time point.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 384
Mean (Standard Deviation)
Unit of Measure: mm
Baseline (n=384) 69.46  (20.84)
Week 24 (n=381) 23.60  (22.68)
10.Secondary Outcome
Title Percent Change From Baseline in Participant's Global Assessment of Disease Activity at Week 24
Hide Description The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. 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 positive change from baseline represents an improvement (reduced level of disease activity).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 381
Mean (Standard Deviation)
Unit of Measure: percent change
61.7  (43.1)
11.Secondary Outcome
Title Physician's Global Assessment of Disease Activity at Baseline and Week 24
Hide Description The physician's global assessment of disease activity is assessed on a 0 to 100 mm 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). The physicians marked the line corresponding to their assessment and the distance from the left edge was measured. A positive change from baseline represents an improvement (reduced level of disease activity).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. All participants with endpoint values collected at the specified timepoints were included in the analysis. n=number of participants analyzed for the given parameter at the specified visit.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 384
Mean (Standard Deviation)
Unit of Measure: mm
Baseline (n=384) 67.32  (16.64)
Week 24 (n=381) 17.92  (18.16)
12.Secondary Outcome
Title Percent Change From Baseline in Physician's Global Assessment of Disease Activity at Week 24
Hide Description The physician's global assessment of disease activity is assessed on a 0 to 100 mm 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). The physicians marked the line corresponding to their assessment and the distance from the left edge was measured. A positive change from baseline represents an improvement (reduced level of disease activity).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 381
Mean (Standard Deviation)
Unit of Measure: percent change
71.2  (38.7)
13.Secondary Outcome
Title HAQ-DI at Baseline and Week 24
Hide Description HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 =without difficulties; 1= with some difficulties; 2=with great difficulties; and 3= unable to perform these actions at all. Minimum score was 0, maximum score was 3. A positive change from baseline represents an improvement (reduced level of impairment).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. All participants with endpoint values collected at the specified timepoints were included in the analysis. n=number of participants analyzed for the given parameter at the specified time point.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 384
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=384) 1.70  (0.63)
Week 24 (n=376) 0.79  (0.68)
14.Secondary Outcome
Title Percent Change From Baseline in HAQ-DI at Week 24
Hide Description HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. A positive change from baseline represents an improvement (reduced level of impairment).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 376
Mean (Standard Deviation)
Unit of Measure: percent change
52.0  (49.3)
15.Secondary Outcome
Title Area Under The Curve (AUC) of the ACR(n)
Hide Description ACR-n was defined as the lowest of 3 values (the percent change in the swollen joint count, the percent change in the tender joint count, and the median of the other 5 measures in the ACR core data set which included Participant's global assessment of pain (VAS), Participant's global assessment of disease activity (VAS), Investigator/Physician's global assessment of disease activity (VAS), Participant's assessment of disability measured by the HAQ-DI Acute phase reactant levels - ESR or CRP). Therefore, a percentage value was assigned to each participant at each timepoint. AUC was calculated for each participant from baseline to Week 112. Mean and standard deviation values are are provided in percent*years.
Time Frame Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 391
Mean (Standard Deviation)
Unit of Measure: percent*years
20.8  (9.4)
16.Secondary Outcome
Title Percentage of Participants Achieving ACR20 Response
Hide Description

ACR20 is defined as 20% improvement in: a) SJC and TJC and b) Three of the following 5 assessments:

  1. Participant's global assessment of pain (VAS)
  2. Participant's global assessment of disease activity (VAS)
  3. Investigator/Physician's global assessment of disease activity (VAS)
  4. Participant's assessment of disability measured by the HAQ-DI
  5. Acute phase reactant levels - ESR or CRP
Time Frame Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at Week 2 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 389
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
40.10
(35.23 to 44.97)
17.Secondary Outcome
Title Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Hide Description The probability of ACR positive response was determined using the GEE.
Time Frame Weeks 2, 4, 8, 12, 16, 20, 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 418
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: odds
Week 2 Odds ACR50
0.10
(0.07 to 0.14)
Week 4 Odds ACR50
0.33
(0.27 to 0.42)
Week 8 Odds ACR50
0.87
(0.72 to 1.05)
Week 12 Odds ACR50
1.39
(1.14 to 1.69)
Week 16 Odds ACR50
1.55
(1.28 to 1.89)
Week 20 Odds ACR50
1.86
(1.52 to 2.27)
Week 24 Odds ACR50
2.39
(1.93 to 2.95)
Week 2 Odds ACR20
0.63
(0.51 to 0.76)
Week 4 Odds ACR20
1.50
(1.24 to 1.83)
Week 8 Odds ACR20
4.80
(3.73 to 6.19)
Week 12 Odds ACR20
4.80
(3.73 to 6.19)
Week 16 Odds ACR20
4.65
(3.61 to 5.97)
Week 20 Odds ACR20
6.46
(4.88 to 8.56)
Week 24 Odds ACR20
6.88
(5.16 to 9.18)
Week 4 Odds ACR70
0.08
(0.06 to 0.12)
Week 8 Odds ACR70
0.27
(0.21 to 0.34)
Week 12 Odds ACR70
0.41
(0.34 to 0.51)
Week 16 Odds ACR70
0.53
(0.44 to 0.65)
Week 20 Odds ACR70
0.75
(0.62 to 0.91)
Week 24 Odds ACR70
0.92
(0.76 to 1.12)
18.Secondary Outcome
Title Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) at Week 24
Hide Description DAS28 calculated from the number of SJC and TJC using the 28 joints count, the ESR (mm/hour) and participant's global assessment of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 (less than or equal to ) ≤3.2 = low disease activity, DAS28 (greater than) >3.2 to 5.1 = moderate to high disease activity.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 399
Mean (Standard Deviation)
Unit of Measure: score on a scale
4.4  (1.6)
19.Secondary Outcome
Title Percentage of Participants With a Response by Categorical DAS28 Responses According to The European League Against Rheumatism (EULAR Response) at Week 24
Hide Description DAS28- based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline >1.2 with DAS28 < 3.2; moderate response: change from baseline >1.2 with DAS28 >3.2 to <5.1 or change from baseline >0.6 to <1.2 with DAS28 <5.1; No response: change from baseline < 0.6 or change from baseline >0.6 and <1.2 with DAS28 >5.1.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 399
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Good Response
68.17
(63.60 to 72.74)
Moderate Response
29.57
(25.10 to 34.05)
No Response
2.26
(0.80 to 3.71)
20.Secondary Outcome
Title AUC of DAS28
Hide Description The AUC was computed using the trapezoidal rule, considering baseline value as 0, through NCSS software. For each participant, AUC for DAS28 units was calculated. Each individual AUC DAS28 value was divided by 52 to have the conversion of AUC DAS28 in unit weeks to AUC DAS28 in unit years, as 1 week is approximately 1/52 years. The set of individual AUC DAS28 was computed as summary statistics.
Time Frame Weeks 2, 4, 8, 12, 16, 20 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 416
Mean (Standard Deviation)
Unit of Measure: scores on a scale * years
11.8  (4.2)
21.Secondary Outcome
Title Fatigue as Assessed Using the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue) Score at Week 24
Hide Description FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. 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 participant's health status.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. All participants with endpoint values collected at Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 403
Mean (Standard Deviation)
Unit of Measure: score on a scale
39.9  (9.4)
22.Secondary Outcome
Title Percentage of Participants Achieving Remission (DAS28 Less Than [<] 2.6) at Week 24
Hide Description DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and participant's global assessment of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 (less than or equal to ) ≤3.2 = low disease activity, DAS28 (greater than) >3.2 to 5.1 = moderate to high disease activity and DAS28<2.6 = remission
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 409
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
48.41
(43.57 to 53.25)
23.Secondary Outcome
Title Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24
Hide Description SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. Total of 3 variables were analyzed (2 composite subscales and vitality score). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 378
Mean (Standard Deviation)
Unit of Measure: score on a scale
General Health 42.5  (12.9)
Physical functioning 63.0  (24.2)
Role limitations due to physical health 64.0  (23.9)
Role limitations due to emotional problems 66.0  (24.1)
Energy/fatigue 48.9  (10.6)
Emotional well-being 54.5  (10.3)
Social functioning 38.2  (12.7)
Pain 63.6  (24.8)
24.Secondary Outcome
Title Mean Change in Rheumatoid Factor (RF) at Week 24 in Participants With Positive RF
Hide Description [Not Specified]
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not analyzed because of inconsistencies in the pooled data between countries.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse events were recorded from the date of first dose of drug administration until the end of study
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tocilizumab
Hide Arm/Group Description Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
All-Cause Mortality
Tocilizumab
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Tocilizumab
Affected / at Risk (%)
Total   30/418 (7.18%) 
Blood and lymphatic system disorders   
Anaemia * 2  1/418 (0.24%) 
Leukopenia NOS * 2  2/418 (0.48%) 
Cardiac disorders   
Bradicardia * 2  1/418 (0.24%) 
Myocardial infarction * 2  1/418 (0.24%) 
Gastrointestinal disorders   
Constipation * 2  1/418 (0.24%) 
Chronic gastrointestinal bleeding * 2  1/418 (0.24%) 
Gastritis * 2  1/418 (0.24%) 
General disorders   
Abscess * 2  1/418 (0.24%) 
Hepatobiliary disorders   
Cholecystitis * 2  1/418 (0.24%) 
Immune system disorders   
Hypersensitivity * 2  1/418 (0.24%) 
Infections and infestations   
Pneumonia * 1  3/418 (0.72%) 
Bronchitis * 2  1/418 (0.24%) 
Septic shock * 2  1/418 (0.24%) 
Appendicitis * 2  1/418 (0.24%) 
Herpes zoster * 2  1/418 (0.24%) 
Cellulitis * 2  3/418 (0.72%) 
Injury, poisoning and procedural complications   
Tendon rupture * 2  1/418 (0.24%) 
Joint dislocation * 2  1/418 (0.24%) 
Fracture * 2  1/418 (0.24%) 
Metabolism and nutrition disorders   
Dehydration * 2  1/418 (0.24%) 
Musculoskeletal and connective tissue disorders   
Rheumatoid arthritis * 2  1/418 (0.24%) 
Intervertebral disc herniation * 2  1/418 (0.24%) 
Intervertebral discitis * 2  1/418 (0.24%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Squamous cell carcinoma * 2  1/418 (0.24%) 
Thyroid cancer * 2  1/418 (0.24%) 
Nervous system disorders   
Headache * 2  1/418 (0.24%) 
Renal and urinary disorders   
Pyelonephritis acute NOS * 2  1/418 (0.24%) 
Respiratory, thoracic and mediastinal disorders   
Respiratory failure * 2  1/418 (0.24%) 
Asthmatic crisis * 2  1/418 (0.24%) 
Skin and subcutaneous tissue disorders   
Urticaria * 2  1/418 (0.24%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
2
Term from vocabulary, MedDRA (16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tocilizumab
Affected / at Risk (%)
Total   324/418 (77.51%) 
Blood and lymphatic system disorders   
Leukopenia NOS * 2  25/418 (5.98%) 
Neutropenia * 2  21/418 (5.02%) 
Gastrointestinal disorders   
Nausea * 2  22/418 (5.26%) 
Stomatitis * 2  22/418 (5.26%) 
Infections and infestations   
Urinary tract infection * 2  41/418 (9.81%) 
Influenza * 2  32/418 (7.66%) 
Pharyngitis * 2  30/418 (7.18%) 
Upper respiratory tract infection * 2  19/418 (4.55%) 
Investigations   
Hepatic enzyme increased * 2  70/418 (16.75%) 
Blood bilirubin increased * 2  19/418 (4.55%) 
Metabolism and nutrition disorders   
Hypercholesterolemia * 1  71/418 (16.99%) 
Hypertriglyceridaemia * 2  39/418 (9.33%) 
Musculoskeletal and connective tissue disorders   
Back pain * 2  22/418 (5.26%) 
Nervous system disorders   
Headache * 2  41/418 (9.81%) 
Vascular disorders   
Hypertension * 2  32/418 (7.66%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
2
Term from vocabulary, MedDRA (16.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann- LaRoche
Phone: 1-800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00754572     History of Changes
Other Study ID Numbers: ML21530
First Submitted: September 17, 2008
First Posted: September 18, 2008
Results First Submitted: June 23, 2014
Results First Posted: May 15, 2015
Last Update Posted: May 15, 2015