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A Study of RoActemra/Actemra and, if Initially Inadequately Responded to RoActemra/Actemra, Followed by MabThera/Rituxan in Patients With Rheumatoid Arthritis

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
rituximab [MabThera/Rituxan]
tocilizumab [RoActemra/Actemra]
tocilizumab [RoActemra/Actemra]
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult patients >/=18 years of age
  • Body weight < /=130kg
  • Active rheumatoid arthritis of at least 6 months duration, diagnosed according to the American College of Rheumatology (ACR) criteria of 1987
  • Disease Activity Score (DAS28) of >3.2
  • Inadequate clinical response to a stable dose of traditional Disease-Modifying Anti-Rheumatic Drugs (DMARD)
  • Have received permitted DMARDs, one or more; current DMARD therapy must have been at stable dose for at least 4 weeks prior to baseline

Exclusion Criteria:

  • Prior treatment with TNF-inhibitors or other biologic DMARD
  • Major surgery (including joint surgery) within eight weeks prior to baseline or planned major surgery within the study duration
  • Functional class IV (American College of Rheumatology classification)
  • Rheumatic autoimmune disease other than rheumatoid arthritis
  • History of or current inflammatory joint disease other than rheumatoid arthritis

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving Remission at Week 16 According to DAS28
The DAS28 was calculated as [0.28 times (x) the square root of number of swollen joints] plus (+) [0.56 x the square root of number of tender joints] + [0.7 x the natural log of erythrocyte sedimentation rate (ESR)] + [0.014 x Visual Analog Scale (VAS) patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.

Secondary Outcome Measures

Percentage of Participants Achieving Remission According to DAS28 at Weeks 4, 8, and 12
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
Percentage of Participants Achieving Remission According to DAS28 at Weeks 16, 20, 24, and 28 Among Participants Treated With 8 Courses of Tocilizumab
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Participants Treated With 8 Courses of Tocilizumab
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Nonresponding Participants Treated With Rituximab
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
Percentage of Participants Achieving Low Disease Activity Score (LDAS) According to DAS28
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x the patient global assessment of disease activity using a VAS]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. LDAS was defined as a DAS28 score <3.2 at the assessment visit.
Percentage of Participants Achieving LDAS According to DAS28 Among Among Nonresponding Participants Treated With Rituximab
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x the patient global assessment of disease activity using a VAS]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. LDAS was defined as a DAS28 score <3.2 at the assessment visit.
Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Week 16
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions >1.2 points from Baseline to the assessment visit were considered clinically relevant.
Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Weeks 4, 8, and 12
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions >1.2 points from Baseline to the assessment visit were considered clinically relevant.
Percentage of Participants Achieving a Clinically Relevant Reduction in DAS28 From Week 16 to Week 32 Among Nonresponding Participants Treated With Rituximab
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions >1.2 points from the reference visit (Week 16) to the assessment visit were considered clinically relevant.
DAS28 Scores During and After Treatment
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
DAS28 Scores During Safety Follow-Up Among Nonresponding Participants Treated With Rituximab
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from Baseline. Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
Percentage of Participants Achieving a Response According to EULAR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit (Week 16). Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from Baseline. Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16
Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate a swollen joint count (SJC) ranging from 0 to 66 swollen joints and a tender joint count (TJC) ranging from 0 to 68 tender joints. Response was defined as a reduction from Baseline of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, Health Assessment Questionnaire Disability Index (HAQ-DI), or C-reactive protein (CRP); plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
Percentage of Participants Achieving a Response According to ACR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab
Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate an SJC ranging from 0 to 66 swollen joints and a TJC ranging from 0 to 68 tender joints. Response was defined as a reduction from the reference visit (Week 16) of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, HAQ-DI, or CRP; plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate an SJC ranging from 0 to 66 swollen joints and a TJC ranging from 0 to 68 tender joints. Response was defined as a reduction from Baseline of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, HAQ-DI, or CRP; plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16
The CDAI was calculated as [SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
Change From Week 16 to 32 in CDAI and SDAI Scores Among Nonresponding Participants Treated With Rituximab
The CDAI was calculated as [SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
The CDAI was calculated as [SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, and 16
Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean hemoglobin at the assessment visit minus mean hemoglobin at Baseline] and expressed in grams per liter (g/L).
Change From Baseline in CRP at Weeks 4, 8, 12, and 16
Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean CRP at the assessment visit minus mean CRP at Baseline] and expressed in milligrams per deciliter (mg/dL).
Change From Baseline in ESR at Weeks 4, 8, 12, and 16
Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean ESR at the assessment visit minus mean ESR at Baseline] and expressed in millimeters per hour (mm/h).
Change in Hemoglobin From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change was calculated as [mean hemoglobin at Week 32 minus mean hemoglobin at Week 16] and expressed in g/L.
Change in CRP From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change was calculated as [mean CRP at Week 32 minus mean CRP at Week 16] and expressed in mg/dL.
Change in ESR From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change was calculated as [mean ESR at Week 32 minus mean ESR at Week 16] and expressed in mm/h.
Change From Baseline in Hemoglobin at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean hemoglobin at the assessment visit minus mean hemoglobin at Baseline] and expressed in g/L.
Change From Baseline in CRP at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean CRP at the assessment visit minus mean CRP at Baseline] and expressed in mg/dL.
Change From Baseline in ESR at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean ESR at the assessment visit minus mean ESR at Baseline] and expressed in mm/h.
Percentage of Participants Withdrawing From the Study for Insufficient Therapeutic Response
Study discontinuation was documented by reason for each participant prematurely withdrawing from the study. The percentage of participants was calculated as the number withdrawing for insufficient therapeutic response divided by the total number of participants who began treatment.
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation [CD] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation [CD] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation [CD] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline to Week 16 in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) >0.2, with greater values indicating a stronger correlation.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) >0.2, with greater values indicating a stronger correlation.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) >0.2, with greater values indicating a stronger correlation.
Mean Number of Work Days Missed Per Week
Work days missed were documented by reason (either rheumatoid arthritis [RA] or other reasons) for each participant over the preceding 7-day period. The mean number of work days missed was calculated by averaging the number of days missed per week among all participants.
Quality of Life as Assessed Using Short Form 36 (SF-36)
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants.
Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as [mean score at Week 16 minus mean score at Baseline].
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as [mean score at Week 32 minus mean score at Week 16].
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as [mean score at Week 32 minus mean score at Week 16].
Quality of Life as Assessed Using HAQ-DI
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants.
Change From Baseline in Quality of Life as Assessed Using HAQ-DI at Week 16
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as [mean score at Week 16 minus mean score at Baseline].
Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Participants Treated With 8 Courses of Tocilizumab
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as [mean score at Week 32 minus the mean score at Week 16].
Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Nonresponding Participants Treated With Rituximab
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as [mean score at Week 32 minus the mean score at Week 16].
Percentage of Participants Achieving a Response According to HAQ-DI Criteria
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. Response was defined as a change in index score >0.22 from Baseline to Week 16.
Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT)
The FACIT-F evaluates quality of life using 5 categories: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and fatigue (FS). Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-General (FACIT-G; range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-Fatigue (FACIT-F) trial outcome index (TOI; range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants.
Change From Baseline in Quality of Life as Assessed Using FACIT at Week 16
The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as [mean score at Week 16 minus mean score at Baseline].
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Participants Treated With 8 Courses of Tocilizumab
The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as [mean score at Week 32 minus mean score at Week 16].
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Nonresponding Participants Treated With Rituximab
The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as [mean score at Week 32 minus mean score at Week 16].

Full Information

First Posted
March 18, 2011
Last Updated
August 5, 2015
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT01332994
Brief Title
A Study of RoActemra/Actemra and, if Initially Inadequately Responded to RoActemra/Actemra, Followed by MabThera/Rituxan in Patients With Rheumatoid Arthritis
Official Title
Efficacy and Safety Study of a Sequential Therapy of Tocilizumab (TCZ) and, if Initially Inadequately Responded to Tocilizumab (TCZ), Followed by Rituximab (RTX) in DMARD-IR Patients With Rheumatoid Arthritis (MIRAI)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
This open-label, multi-center, two-arm, uncontrolled and non-randomized study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with rheumatoid arthritis. Patients will receive 8 mg/kg RoActemra/Actemra intravenously every 4 weeks for 12 weeks and - if adequately responded - for further 12 weeks. Patients, who show an inadequate clinical response after the first 12 weeks to RoActemra/Actemra, will receive 1 g MabThera/Rituxan (rituximab) intravenously at Week 16 and 18. The anticipated time of study treatment is 32 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
519 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
rituximab [MabThera/Rituxan]
Intervention Description
1 g intravenously at Week 16 and 18
Intervention Type
Drug
Intervention Name(s)
tocilizumab [RoActemra/Actemra]
Intervention Description
8 mg/kg intravenously every 4 weeks for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
tocilizumab [RoActemra/Actemra]
Intervention Description
8 mg/kg intravenously every 4 weeks from Week 16 to Week 28
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving Remission at Week 16 According to DAS28
Description
The DAS28 was calculated as [0.28 times (x) the square root of number of swollen joints] plus (+) [0.56 x the square root of number of tender joints] + [0.7 x the natural log of erythrocyte sedimentation rate (ESR)] + [0.014 x Visual Analog Scale (VAS) patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
Time Frame
Week 16
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving Remission According to DAS28 at Weeks 4, 8, and 12
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
Time Frame
Weeks 4, 8, and 12
Title
Percentage of Participants Achieving Remission According to DAS28 at Weeks 16, 20, 24, and 28 Among Participants Treated With 8 Courses of Tocilizumab
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
Time Frame
Weeks 16, 20, 24, and 28
Title
Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Participants Treated With 8 Courses of Tocilizumab
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
Time Frame
Week 32
Title
Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Nonresponding Participants Treated With Rituximab
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
Time Frame
Week 32
Title
Percentage of Participants Achieving Low Disease Activity Score (LDAS) According to DAS28
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x the patient global assessment of disease activity using a VAS]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. LDAS was defined as a DAS28 score <3.2 at the assessment visit.
Time Frame
Week 16
Title
Percentage of Participants Achieving LDAS According to DAS28 Among Among Nonresponding Participants Treated With Rituximab
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x the patient global assessment of disease activity using a VAS]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. LDAS was defined as a DAS28 score <3.2 at the assessment visit.
Time Frame
Week 32
Title
Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Week 16
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions >1.2 points from Baseline to the assessment visit were considered clinically relevant.
Time Frame
Baseline and Week 16
Title
Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Weeks 4, 8, and 12
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions >1.2 points from Baseline to the assessment visit were considered clinically relevant.
Time Frame
Baseline and Weeks 4, 8, and 12
Title
Percentage of Participants Achieving a Clinically Relevant Reduction in DAS28 From Week 16 to Week 32 Among Nonresponding Participants Treated With Rituximab
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions >1.2 points from the reference visit (Week 16) to the assessment visit were considered clinically relevant.
Time Frame
Weeks 16 and 32
Title
DAS28 Scores During and After Treatment
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
Time Frame
Baseline and Weeks 4, 8, 12, 16
Title
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, and 32
Title
DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 24, and 32
Title
DAS28 Scores During Safety Follow-Up Among Nonresponding Participants Treated With Rituximab
Description
The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
Time Frame
Weeks 40, 48, 56, and 66
Title
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16
Description
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from Baseline. Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
Time Frame
Baseline and Weeks 4, 8, 12, and 16
Title
Percentage of Participants Achieving a Response According to EULAR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab
Description
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit (Week 16). Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
Time Frame
Weeks 16 and 32
Title
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Description
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from Baseline. Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
Time Frame
Baseline and Weeks 20, 24, 28, and 32
Title
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16
Description
Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate a swollen joint count (SJC) ranging from 0 to 66 swollen joints and a tender joint count (TJC) ranging from 0 to 68 tender joints. Response was defined as a reduction from Baseline of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, Health Assessment Questionnaire Disability Index (HAQ-DI), or C-reactive protein (CRP); plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
Time Frame
Baseline and Weeks 4, 8, 12, and 16
Title
Percentage of Participants Achieving a Response According to ACR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab
Description
Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate an SJC ranging from 0 to 66 swollen joints and a TJC ranging from 0 to 68 tender joints. Response was defined as a reduction from the reference visit (Week 16) of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, HAQ-DI, or CRP; plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
Time Frame
Weeks 16 and 32
Title
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Description
Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate an SJC ranging from 0 to 66 swollen joints and a TJC ranging from 0 to 68 tender joints. Response was defined as a reduction from Baseline of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, HAQ-DI, or CRP; plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
Time Frame
Baseline and Weeks 20, 24, 28, and 32
Title
Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16
Description
The CDAI was calculated as [SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
Time Frame
Baseline and Weeks 4, 8, 12, and 16
Title
Change From Week 16 to 32 in CDAI and SDAI Scores Among Nonresponding Participants Treated With Rituximab
Description
The CDAI was calculated as [SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
Time Frame
Weeks 16 and 32
Title
Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Description
The CDAI was calculated as [SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
Time Frame
Baseline and Weeks 20, 24, 28, and 32
Title
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, and 16
Description
Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean hemoglobin at the assessment visit minus mean hemoglobin at Baseline] and expressed in grams per liter (g/L).
Time Frame
Baseline and Weeks 4, 8, 12, and 16
Title
Change From Baseline in CRP at Weeks 4, 8, 12, and 16
Description
Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean CRP at the assessment visit minus mean CRP at Baseline] and expressed in milligrams per deciliter (mg/dL).
Time Frame
Baseline and Weeks 4, 8, 12, and 16
Title
Change From Baseline in ESR at Weeks 4, 8, 12, and 16
Description
Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean ESR at the assessment visit minus mean ESR at Baseline] and expressed in millimeters per hour (mm/h).
Time Frame
Baseline and Weeks 4, 8, 12, and 16
Title
Change in Hemoglobin From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
Description
Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change was calculated as [mean hemoglobin at Week 32 minus mean hemoglobin at Week 16] and expressed in g/L.
Time Frame
Weeks 16 and 32
Title
Change in CRP From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
Description
Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change was calculated as [mean CRP at Week 32 minus mean CRP at Week 16] and expressed in mg/dL.
Time Frame
Weeks 16 and 32
Title
Change in ESR From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
Description
Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change was calculated as [mean ESR at Week 32 minus mean ESR at Week 16] and expressed in mm/h.
Time Frame
Weeks 16 and 32
Title
Change From Baseline in Hemoglobin at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Description
Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean hemoglobin at the assessment visit minus mean hemoglobin at Baseline] and expressed in g/L.
Time Frame
Baseline and Weeks 20, 24, 28, and 32
Title
Change From Baseline in CRP at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Description
Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean CRP at the assessment visit minus mean CRP at Baseline] and expressed in mg/dL.
Time Frame
Baseline and Weeks 20, 24, 28, and 32
Title
Change From Baseline in ESR at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Description
Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean ESR at the assessment visit minus mean ESR at Baseline] and expressed in mm/h.
Time Frame
Baseline and Weeks 20, 24, 28, and 32
Title
Percentage of Participants Withdrawing From the Study for Insufficient Therapeutic Response
Description
Study discontinuation was documented by reason for each participant prematurely withdrawing from the study. The percentage of participants was calculated as the number withdrawing for insufficient therapeutic response divided by the total number of participants who began treatment.
Time Frame
Baseline to Week 16
Title
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission
Description
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation [CD] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
Time Frame
Baseline
Title
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab
Description
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation [CD] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
Time Frame
Baseline
Title
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab
Description
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation [CD] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
Time Frame
Baseline
Title
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission
Description
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline to Week 16 in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) >0.2, with greater values indicating a stronger correlation.
Time Frame
Baseline and Week 16
Title
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Description
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) >0.2, with greater values indicating a stronger correlation.
Time Frame
Baseline and Weeks 16, 24, and 32
Title
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab
Description
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) >0.2, with greater values indicating a stronger correlation.
Time Frame
Baseline and Weeks 16, 32, 40, 48, and 66
Title
Mean Number of Work Days Missed Per Week
Description
Work days missed were documented by reason (either rheumatoid arthritis [RA] or other reasons) for each participant over the preceding 7-day period. The mean number of work days missed was calculated by averaging the number of days missed per week among all participants.
Time Frame
Baseline and Week 16
Title
Quality of Life as Assessed Using Short Form 36 (SF-36)
Description
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants.
Time Frame
Baseline and Week 16
Title
Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16
Description
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as [mean score at Week 16 minus mean score at Baseline].
Time Frame
Baseline and Week 16
Title
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab
Description
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as [mean score at Week 32 minus mean score at Week 16].
Time Frame
Weeks 16 and 32
Title
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab
Description
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as [mean score at Week 32 minus mean score at Week 16].
Time Frame
Weeks 16 and 32
Title
Quality of Life as Assessed Using HAQ-DI
Description
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants.
Time Frame
Baseline and Week 16
Title
Change From Baseline in Quality of Life as Assessed Using HAQ-DI at Week 16
Description
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as [mean score at Week 16 minus mean score at Baseline].
Time Frame
Baseline and Week 16
Title
Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Participants Treated With 8 Courses of Tocilizumab
Description
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as [mean score at Week 32 minus the mean score at Week 16].
Time Frame
Weeks 16 and 32
Title
Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Nonresponding Participants Treated With Rituximab
Description
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as [mean score at Week 32 minus the mean score at Week 16].
Time Frame
Weeks 16 and 32
Title
Percentage of Participants Achieving a Response According to HAQ-DI Criteria
Description
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. Response was defined as a change in index score >0.22 from Baseline to Week 16.
Time Frame
Baseline and Week 16
Title
Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT)
Description
The FACIT-F evaluates quality of life using 5 categories: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and fatigue (FS). Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-General (FACIT-G; range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-Fatigue (FACIT-F) trial outcome index (TOI; range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants.
Time Frame
Baseline and Week 16
Title
Change From Baseline in Quality of Life as Assessed Using FACIT at Week 16
Description
The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as [mean score at Week 16 minus mean score at Baseline].
Time Frame
Baseline and Week 16
Title
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Participants Treated With 8 Courses of Tocilizumab
Description
The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as [mean score at Week 32 minus mean score at Week 16].
Time Frame
Weeks 16 and 32
Title
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Nonresponding Participants Treated With Rituximab
Description
The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as [mean score at Week 32 minus mean score at Week 16].
Time Frame
Weeks 16 and 32

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult patients >/=18 years of age Body weight < /=130kg Active rheumatoid arthritis of at least 6 months duration, diagnosed according to the American College of Rheumatology (ACR) criteria of 1987 Disease Activity Score (DAS28) of >3.2 Inadequate clinical response to a stable dose of traditional Disease-Modifying Anti-Rheumatic Drugs (DMARD) Have received permitted DMARDs, one or more; current DMARD therapy must have been at stable dose for at least 4 weeks prior to baseline Exclusion Criteria: Prior treatment with TNF-inhibitors or other biologic DMARD Major surgery (including joint surgery) within eight weeks prior to baseline or planned major surgery within the study duration Functional class IV (American College of Rheumatology classification) Rheumatic autoimmune disease other than rheumatoid arthritis History of or current inflammatory joint disease other than rheumatoid arthritis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Aachen
ZIP/Postal Code
52064
Country
Germany
City
Bad Aibling
ZIP/Postal Code
83043
Country
Germany
City
Bad Bramstedt
ZIP/Postal Code
24576
Country
Germany
City
Bad Nauheim
ZIP/Postal Code
61231
Country
Germany
City
Bad Staffelstein
ZIP/Postal Code
96231
Country
Germany
City
Bayreuth
ZIP/Postal Code
95445
Country
Germany
City
Berlin
ZIP/Postal Code
10117
Country
Germany
City
Berlin
ZIP/Postal Code
10435
Country
Germany
City
Berlin
ZIP/Postal Code
12161
Country
Germany
City
Berlin
ZIP/Postal Code
12435
Country
Germany
City
Berlin
ZIP/Postal Code
13055
Country
Germany
City
Berlin
ZIP/Postal Code
13125
Country
Germany
City
Berlin
ZIP/Postal Code
14129
Country
Germany
City
Blaubeuren
ZIP/Postal Code
89143
Country
Germany
City
Bonn
ZIP/Postal Code
53111
Country
Germany
City
Bruchhausen-Vilsen
ZIP/Postal Code
27305
Country
Germany
City
Chemnitz
ZIP/Postal Code
09130
Country
Germany
City
Donaueschingen
ZIP/Postal Code
78166
Country
Germany
City
Dresden
ZIP/Postal Code
01067
Country
Germany
City
Dresden
ZIP/Postal Code
01097
Country
Germany
City
Dresden
ZIP/Postal Code
01109
Country
Germany
City
Dresden
ZIP/Postal Code
01307
Country
Germany
City
Düsseldorf
ZIP/Postal Code
40217
Country
Germany
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
City
Erfurt
ZIP/Postal Code
99096
Country
Germany
City
Essen
ZIP/Postal Code
45239
Country
Germany
City
Frankfurt Am Main
ZIP/Postal Code
60590
Country
Germany
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
City
Giessen
ZIP/Postal Code
35392
Country
Germany
City
Gommern
ZIP/Postal Code
39245
Country
Germany
City
Goslar
ZIP/Postal Code
38642
Country
Germany
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
City
Halle
ZIP/Postal Code
06108
Country
Germany
City
Halle
ZIP/Postal Code
06120
Country
Germany
City
Halle
ZIP/Postal Code
06128
Country
Germany
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
City
Hamburg
ZIP/Postal Code
22147
Country
Germany
City
Hamburg
ZIP/Postal Code
22767
Country
Germany
City
Hannover
ZIP/Postal Code
30625
Country
Germany
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
City
Heidelberg
ZIP/Postal Code
69121
Country
Germany
City
Herne
ZIP/Postal Code
44652
Country
Germany
City
Hildesheim
ZIP/Postal Code
31134
Country
Germany
City
Hofheim
ZIP/Postal Code
65719
Country
Germany
City
Jena
ZIP/Postal Code
07747
Country
Germany
City
Kiel
ZIP/Postal Code
24105
Country
Germany
City
Köln
ZIP/Postal Code
50679
Country
Germany
City
Köln
ZIP/Postal Code
50924
Country
Germany
City
Köln
ZIP/Postal Code
51149
Country
Germany
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
City
Leipzig
ZIP/Postal Code
04109
Country
Germany
City
Lingen
ZIP/Postal Code
49808
Country
Germany
City
Ludwigsfelde
ZIP/Postal Code
14974
Country
Germany
City
Mainz
ZIP/Postal Code
55131
Country
Germany
City
Muenchen
ZIP/Postal Code
80336
Country
Germany
City
Mönchengladbach
ZIP/Postal Code
41061
Country
Germany
City
München
ZIP/Postal Code
80335
Country
Germany
City
München
ZIP/Postal Code
81541
Country
Germany
City
Naumburg
ZIP/Postal Code
06628
Country
Germany
City
Naunhof
ZIP/Postal Code
04683
Country
Germany
City
Neuss
ZIP/Postal Code
41460
Country
Germany
City
Neuss
ZIP/Postal Code
41462
Country
Germany
City
Nienburg
ZIP/Postal Code
31582
Country
Germany
City
Olsberg
ZIP/Postal Code
59939
Country
Germany
City
Osnabrück
ZIP/Postal Code
49074
Country
Germany
City
Plochingen
ZIP/Postal Code
73207
Country
Germany
City
Potsdam
ZIP/Postal Code
14469
Country
Germany
City
Ratingen
ZIP/Postal Code
40882
Country
Germany
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
City
Rendsburg
ZIP/Postal Code
24768
Country
Germany
City
Rheine
ZIP/Postal Code
48431
Country
Germany
City
Rostock
ZIP/Postal Code
18059
Country
Germany
City
Saarbruecken
ZIP/Postal Code
66111
Country
Germany
City
Sendenhorst
ZIP/Postal Code
48324
Country
Germany
City
Stuttgart
ZIP/Postal Code
70178
Country
Germany
City
Stuttgart
ZIP/Postal Code
70372
Country
Germany
City
Traunstein
ZIP/Postal Code
83278
Country
Germany
City
Trier
ZIP/Postal Code
54292
Country
Germany
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
City
Ulm
ZIP/Postal Code
89081
Country
Germany
City
Wiesbaden
ZIP/Postal Code
65189
Country
Germany
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

A Study of RoActemra/Actemra and, if Initially Inadequately Responded to RoActemra/Actemra, Followed by MabThera/Rituxan in Patients With Rheumatoid Arthritis

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