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An Observational Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis And Inadequate Response Or Intolerance to a First Anti-TNF Alpha Therapy

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ClinicalTrials.gov Identifier: NCT01592292
Recruitment Status : Completed
First Posted : May 7, 2012
Results First Posted : August 22, 2016
Last Update Posted : August 22, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Condition Rheumatoid Arthritis
Interventions Drug: Rituximab
Drug: Adalimumab
Drug: Etanercept
Drug: Infliximab
Enrollment 90
Recruitment Details  
Pre-assignment Details The arm Other anti-TNF agent consisting of participants treated with adalimumab, etanercept and infliximab was divided into individual treatment groups only for the purpose of Participant flow reporting. All other analyses were performed in Rituximab versus Other anti-TNF agent.
Arm/Group Title Rituximab Other Anti-TNF Agent: Adalimumab Other Anti-TNF Agent: Etanercept Other Anti-TNF Agent: Infliximab
Hide Arm/Group Description Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months. Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving adalimumab as per physician's discretion for RA treatment were observed for 12 months. Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving etanercept as per physician's discretion for RA treatment were observed for 12 months. Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving infliximab as per physician's discretion for RA treatment were observed for 12 months.
Period Title: Overall Study
Started 46 20 13 11
Intention to Treat (ITT) Set 34 [1] 13 10 8
Standard Population Set (SPS) 31 [2] 10 7 7
Completed 40 [3] 15 10 10
Not Completed 6 5 3 1
Reason Not Completed
Follow-up loss             3             3             1             0
Withdrew consent             2             1             0             0
Other             1             1             2             1
[1]
Excluding primary effect evaluation omission.
[2]
Excluding participants with change of administration drug or suspension of drug administration.
[3]
Participants who completed 12 months visit.
Arm/Group Title Rituximab Other Anti-TNF Agent Total
Hide Arm/Group Description Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months. Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months. Total of all reporting groups
Overall Number of Baseline Participants 34 31 65
Hide Baseline Analysis Population Description
The intent to treat (ITT) set included participants who offered end-point results among the participants who received the study drugs after enrollment and met all inclusion/exclusion criteria.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants 31 participants 65 participants
20-29 years 0 2 2
30-39 years 4 4 8
40-49 years 7 7 14
50-59 years 6 7 13
60-69 years 15 6 21
70-79 years 2 5 7
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 31 participants 65 participants
Female
25
  73.5%
26
  83.9%
51
  78.5%
Male
9
  26.5%
5
  16.1%
14
  21.5%
1.Primary Outcome
Title Efficacy: Mean Change From Baseline in DAS28 at Month 6 in Intention to Treat (ITT) Population
Hide Description DAS28 is calculated from the number of swollen joints and tender joints using the 28-joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and patient's global assessment of disease activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 (minimum score) to 10 (maximum score); higher scores indicated greater affectation due to disease activity. A DAS28 score of less than or equal to (=<) 3.2 = low disease activity, a DAS28 score of >3.2 to 5.1 = moderate to high disease activity.
Time Frame Baseline and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included participants who offered end-point results among participants who received study drugs after enrollment and met all inclusion/exclusion criteria.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 34 31
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 6.35  (1.14) 5.54  (1.14)
Change at Month 6 -1.89  (1.73) -1.80  (1.53)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3037
Comments Change in DAS28 at Month 6 was performed using analysis of covariance (ANCOVA) model with baseline DAS28 score and rheumatoid factor (RF) status as covariate values.
Method ANCOVA
Comments [Not Specified]
2.Primary Outcome
Title Efficacy: Mean Change From Baseline in DAS28 at Month 6 in Standard Population Set (SPS)
Hide Description DAS28 is calculated from the number of swollen joints and tender joints using the 28-joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 (minimum score) to 10 (maximum score); higher scores indicated greater affectation due to disease activity. A DAS28 score of less than or equal to (=<) 3.2 = low disease activity, a DAS28 score of >3.2 to 5.1 = moderate to high disease activity.
Time Frame Baseline and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
The SPS included participants who maintained the secondary biological agent treatment selected for the first time for 6 months among the participants included in the ITT set.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 31 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 6.30  (1.18) 5.47  (1.04)
Change at Month 6 -1.74  (1.59) -1.91  (1.53)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0951
Comments Change in DAS28 at Month 6 was performed using ANCOVA model with baseline DAS28 score and rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Efficacy: Mean Change From Baseline in DAS28 at Month 12
Hide Description DAS28 is calculated from the number of swollen joints and tender joints using the 28-joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 (minimum score) to 10 (maximum score); higher scores indicated greater affectation due to disease activity. A DAS28 score of less than or equal to (=<) 3.2 = low disease activity, a DAS28 score of >3.2 to 5.1 = moderate to high disease activity.
Time Frame Baseline and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on participants who were administered with secondary biological agent continuously without change or suspension for 12 months. Here, 'n' represents the participants who were evaluable at specific time point.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 24 17
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=24, 17) 6.28  (1.27) 5.49  (0.92)
Change at Month 12 (n=22, 16) -2.30  (1.52) -2.29  (1.36)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2390
Comments Change in DAS28 at Month 12 was performed using ANCOVA model with baseline DAS28 score and rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Efficacy: Mean Change From Baseline in Tender Joint Count (TJC) at Month 6 and 12 in Intention to Treat (ITT) Population
Hide Description TJC is a clinical method to quantify abnormalities in participants with RA. It is associated with the level of pain. The number of tender joints were scored as tender=1 and not tender=0, and counted. A negative change from baseline represents an improvement (a reduction in the number of tender joints).
Time Frame Baseline, Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included participants who offered end-point results among the participants who received study drugs after enrollment and met all inclusion/exclusion criteria. Here, 'n' represents the participants who were evaluable at specific time point.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 34 31
Mean (Standard Deviation)
Unit of Measure: number of tender joints
Baseline (n=34, 31) 13.38  (7.22) 8.81  (6.88)
Change at Month 6 (n=34, 31) -8.21  (7.54) -6.32  (7.06)
Change at Month 12 (n=29, 24) -9.48  (7.02) -5.96  (6.40)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3212
Comments Change in TJC at Month 6 was performed using ANCOVA model with baseline TJC and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7097
Comments Change in TJC at Month 12 was performed using ANCOVA model with baseline TJC and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
5.Secondary Outcome
Title Efficacy: Mean Change From Baseline in Tender Joint Count (TJC) at Month 6 and 12 in Standard Population Set (SPS)
Hide Description TJC is a clinical method to quantify abnormalities in participants with RA. It is associated with the level of pain. The number of tender joints were scored as tender=1 and not tender=0, and counted. A negative change from baseline represents an improvement (a reduction in the number of tender joints).
Time Frame Baseline, Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The SPS included participants who maintained the secondary biological agent treatment selected for the first time for 6 months among the participants included in the ITT set. Here, 'n' represents the participants who were evaluable at specific time point.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 31 24
Mean (Standard Deviation)
Unit of Measure: number of tender joints
Baseline (n=31, 24) 12.87  (7.32) 7.79  (5.99)
Change at Month 6 (n=31, 24) -7.68  (7.55) -5.79  (6.17)
Change at Month 6 (n=26, 20) -8.62  (6.89) -5.80  (5.78)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2444
Comments Change in TJC at Month 6 was performed using ANCOVA with baseline TJC and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3903
Comments Change in TJC at Month 12 was performed using ANCOVA model with baseline TJC and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
6.Secondary Outcome
Title Efficacy: Mean Change From Baseline in Swollen Joint Count (SJC) at Month 6 and 12 in Intention to Treat (ITT) Population
Hide Description SJC is a clinical method to quantify abnormalities in participants with RA. It reflects the amount of inflamed synovial tissue. The number of swollen joints were scored as swollen=1 and not swollen=0, and counted. A negative change from baseline represents an improvement (a reduction in the number of swollen joints).
Time Frame Baseline, Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included participants who offered end-point results among the participants who received study drugs after enrollment and met all inclusion/exclusion criteria. Here, 'n' represents the participants who were evaluable at specific time point.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 34 31
Mean (Standard Deviation)
Unit of Measure: number of swollen joints
Baseline (n=34, 31) 11.24  (6.78) 7.52  (6.63)
Change at Month 6 (n=34, 31) -7.00  (6.86) -5.10  (6.48)
Change at Month 12 (n-29, 24) -8.62  (6.52) -4.29  (5.81)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5306
Comments Change in SJC at Month 6 was performed using ANCOVA model with baseline SJC and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2542
Comments Change in SJC at Month 12 was performed using ANCOVA model with baseline SJC and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
7.Secondary Outcome
Title Efficacy: Mean Change From Baseline in Swollen Joint Count (SJC) at Month 6 and 12 in Standard Population Set (SPS)
Hide Description SJC is a clinical method to quantify abnormalities in participants with RA. It reflects the amount of inflamed synovial tissue. The number of swollen joints were scored as swollen=1 and not swollen=0, and counted. A negative change from baseline represents an improvement (a reduction in the number of swollen joints).
Time Frame Baseline, Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The SPS included participants who maintained the secondary biological agent treatment selected for the first time for 6 months among the participants included in the ITT set. Here, 'n' represents the participants who were evaluable at specific time point.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 31 24
Mean (Standard Deviation)
Unit of Measure: number of swollen joints
Baseline (n=31, 24) 11.16  (7.10) 7.13  (6.15)
Change at Month 6 (n=31, 24) -6.74  (7.02) -5.21  (6.35)
Change at Month 6 (n=26, 20) -8.31  (6.80) -5.00  (6.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2549
Comments Change in SJC at Month 6 was performed using ANCOVA model with baseline SJC and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7644
Comments Change in SJC at Month 12 was performed using ANCOVA model with baseline SJC and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
8.Secondary Outcome
Title Efficacy: Mean Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Month 6 and 12 in Intention to Treat (ITT) Population
Hide Description ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline represents a reduction in inflammation.
Time Frame Baseline, Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included participants who offered end-point results among the participants who received study drugs after enrollment and met all inclusion/exclusion criteria. Here, 'n' represents the participants who were evaluable at specific time point.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 34 31
Mean (Standard Deviation)
Unit of Measure: millimeter/hour (mm/hr)
Baseline (n=34, 31) 67.00  (27.50) 60.77  (30.76)
Change at Month 6 (n=34, 31) -19.35  (27.03) -15.55  (33.19)
Change at Month 12 (n=31, 25) -20.36  (29.84) -21.64  (28.16)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8987
Comments Change in ESR at Month 6 was performed using ANCOVA model with baseline ESR and rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5808
Comments Change in ESR at Month 12 was performed using ANCOVA model with baseline ESR and rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
9.Secondary Outcome
Title Efficacy: Mean Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Month 6 and 12 in Standard Population Set (SPS)
Hide Description ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline represents a reduction in inflammation.
Time Frame Baseline, Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The SPS included participants who maintained the secondary biological agent treatment selected for the first time for 6 months among the participants included in the ITT set. Here, 'n' represents the participants who were evaluable at specific time point.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 31 24
Mean (Standard Deviation)
Unit of Measure: mm/hr
Baseline (n=31, 24) 67.55  (28.76) 61.58  (29.47)
Change at Month 6 (n=31, 24) -19.13  (26.96) -23.21  (31.33)
Change at Month 12 (n=28, 20) -21.54  (30.51) -22.10  (26.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2282
Comments Change in ESR at Month 6 was performed using ANCOVA model with baseline ESR and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5849
Comments Change in ESR at Month 12 was performed using ANCOVA model with baseline ESR and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
10.Secondary Outcome
Title Efficacy: Mean Change From Baseline in C-reactive Protein (CRP) at Month 6 and 12 in Intention to Treat (ITT) Population
Hide Description CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA. A negative change from baseline represents a reduction in inflammation.
Time Frame Baseline, Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included participants who offered end-point results among the participants who received study drugs after enrollment and met all inclusion/exclusion criteria. Here, 'n' represents the participants who were evaluable at specific time point.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 34 31
Mean (Standard Deviation)
Unit of Measure: milligram/deciliter (mg/dL)
Baseline (n=34, 31) 3.53  (3.07) 2.56  (2.73)
Change at Month 6 (n=34, 30) -1.84  (3.43) -0.74  (3.25)
Change at Month 12 (n=31, 25) -0.69  (6.56) -1.51  (2.61)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4900
Comments Change in CRP at Month 6 was performed using ANCOVA model with baseline CRP and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1826
Comments Change in CRP at Month 12 was performed using ANCOVA model with baseline CRP and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
11.Secondary Outcome
Title Efficacy: Mean Change From Baseline in C-reactive Protein (CRP) at Month 6 and 12 in Standard Population Set (SPS)
Hide Description CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA. A negative change from baseline represents a reduction in inflammation.
Time Frame Baseline, Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The SPS included participants who maintained the secondary biological agent treatment selected for the first time for 6 months among the participants included in the ITT set. Here, 'n' represents the participants who were evaluable at specific time point.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 31 24
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline (n=31, 24) 3.53  (3.17) 2.59  (2.78)
Change at Month 6 (n=31, 24) -1.79  (3.56) -1.63  (2.37)
Change at Month 12 (n=28, 20) -0.60  (6.88) -1.59  (2.73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1894
Comments Change in CRP at Month 6 was performed using ANCOVA model with baseline CRP and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1805
Comments Change in CRP at Month 12 was performed using ANCOVA model with baseline CRP and baseline rheumatoid factor status as covariate values.
Method ANCOVA
Comments [Not Specified]
12.Secondary Outcome
Title Efficacy: Health Assessment Questionnaire-Disability Index (HAQ-DI) in Intention to Treat (ITT) Population
Hide Description The HAQ-DI is a participant-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). The overall HAQ-DI score is the average of each of the 8 category scores and ranges from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set included participants who offered end-point results among the participants who received study drugs after enrollment and met all inclusion/exclusion criteria. Here number of participants analyzed is the total participants who were evaluable for this outcome measure.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 33 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.69  (0.70) 0.40  (0.48)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0568
Comments Change in HAQ-DI at Month 6 was performed using ANCOVA model with baseline rheumatoid factor status as covariate value.
Method ANCOVA
Comments [Not Specified]
13.Secondary Outcome
Title Efficacy: Health Assessment Questionnaire-Disability Index (HAQ-DI) in Standard Population Set (SPS)
Hide Description The HAQ-DI is a participant-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). The overall HAQ-DI score is the average of each of the 8 category scores and ranges from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability.
Time Frame Month 6
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Hide Analysis Population Description
The SPS included participants who maintained the secondary biological agent treatment selected for the first time for 6 months among the participants included in the ITT set. Here number of participants analyzed is the total participants who were evaluable for this outcome measure.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 30 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.73  (0.71) 0.46  (0.52)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Other Anti-TNF Agent
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1167
Comments Change in HAQ-DI at Month 6 was performed using ANCOVA model with baseline rheumatoid factor status as covariate value.
Method ANCOVA
Comments [Not Specified]
14.Secondary Outcome
Title Safety: Number of Participants With Adverse Events (AE), Adverse Drug Reactions (ADR) and Serious Adverse Events
Hide Description An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. ADRs were defined as any response to a drug which was noxious and unintended, and which occurred at dose normally used related to the pharmacological properties. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.
Time Frame Baseline up to Month 12
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Hide Analysis Population Description
The ITT set included participants who offered end-point results among the participants who received study drugs after enrollment and met all inclusion/exclusion criteria.
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description:
Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months.
Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
Overall Number of Participants Analyzed 34 31
Measure Type: Number
Unit of Measure: participants
Adverse events 8 8
Adverse drug reactions (ADR) 4 5
Serious adverse events (SAE) 3 0
Time Frame Baseline up to Month 12
Adverse Event Reporting Description The ITT set included participants who offered end-point results among the participants who received the study drugs after enrollment and met all inclusion/exclusion criteria.
 
Arm/Group Title Rituximab Other Anti-TNF Agent
Hide Arm/Group Description Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months. Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent (adalimumab, etanercept or infliximab) as per physician's discretion for RA treatment were observed for 12 months.
All-Cause Mortality
Rituximab Other Anti-TNF Agent
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Rituximab Other Anti-TNF Agent
Affected / at Risk (%) Affected / at Risk (%)
Total   3/34 (8.82%)   0/31 (0.00%) 
Immune system disorders     
Anaphylactoid reaction  1  1/34 (2.94%)  0/31 (0.00%) 
Infections and infestations     
Pneumonia  1  1/34 (2.94%)  0/31 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/34 (2.94%)  0/31 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rituximab Other Anti-TNF Agent
Affected / at Risk (%) Affected / at Risk (%)
Total   0/34 (0.00%)   2/31 (6.45%) 
Gastrointestinal disorders     
Diarrhoea  1  0/34 (0.00%)  2/31 (6.45%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
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 only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01592292    
Other Study ID Numbers: ML27923
First Submitted: April 11, 2012
First Posted: May 7, 2012
Results First Submitted: May 3, 2016
Results First Posted: August 22, 2016
Last Update Posted: August 22, 2016