A Study of RoActemra/Actemra and, if Initially Inadequately Responded to RoActemra/Actemra, Followed by MabThera/Rituxan in Patients With Rheumatoid Arthritis
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01332994
Collaborator
(none)
519
83
2
35.1
6.3
0.2
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
519 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date
:
Mar 1, 2011
Actual Primary Completion Date
:
Feb 1, 2014
Actual Study Completion Date
:
Feb 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg intravenously every 4 weeks for 12 weeks.
Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg intravenously every 4 weeks from Week 16 to Week 28
|
| Experimental: 2
|
Drug: rituximab [MabThera/Rituxan]
1 g intravenously at Week 16 and 18
Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg intravenously every 4 weeks for 12 weeks.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving Remission at Week 16 According to DAS28 [Week 16]
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 [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 [Weeks 16, 20, 24, and 28]
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 [Week 32]
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 [Week 32]
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 [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 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 [Week 32]
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 [Baseline and 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 [Baseline and 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 [Weeks 16 and 32]
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 [Baseline and Weeks 4, 8, 12, 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.
- DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab [Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, and 32]
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 [Baseline and Weeks 4, 8, 12, 16, 24, and 32]
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 [Weeks 40, 48, 56, and 66]
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 [Baseline and 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 [Weeks 16 and 32]
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 [Baseline and Weeks 20, 24, 28, and 32]
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 [Baseline and 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 [Weeks 16 and 32]
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 [Baseline and Weeks 20, 24, 28, and 32]
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 [Baseline and 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 [Weeks 16 and 32]
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 [Baseline and Weeks 20, 24, 28, and 32]
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 [Baseline and 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 [Baseline and 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 [Baseline and 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 [Weeks 16 and 32]
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 [Weeks 16 and 32]
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 [Weeks 16 and 32]
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 [Baseline and Weeks 20, 24, 28, and 32]
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 [Baseline and Weeks 20, 24, 28, and 32]
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 [Baseline and Weeks 20, 24, 28, and 32]
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 [Baseline to Week 16]
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 [Baseline]
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 [Baseline]
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 [Baseline]
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 [Baseline and Week 16]
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 [Baseline and Weeks 16, 24, and 32]
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 [Baseline and Weeks 16, 32, 40, 48, and 66]
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 [Baseline and Week 16]
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) [Baseline and 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.
- Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16 [Baseline and 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 [Weeks 16 and 32]
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 [Weeks 16 and 32]
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 [Baseline and 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.
- Change From Baseline in Quality of Life as Assessed Using HAQ-DI at Week 16 [Baseline and 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 [Weeks 16 and 32]
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 [Weeks 16 and 32]
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 [Baseline and 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. 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) [Baseline and Week 16]
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 [Baseline and 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 [Weeks 16 and 32]
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 [Weeks 16 and 32]
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].
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aachen | Germany | 52064 | ||
| 2 | Bad Aibling | Germany | 83043 | ||
| 3 | Bad Bramstedt | Germany | 24576 | ||
| 4 | Bad Nauheim | Germany | 61231 | ||
| 5 | Bad Staffelstein | Germany | 96231 | ||
| 6 | Bayreuth | Germany | 95445 | ||
| 7 | Berlin | Germany | 10117 | ||
| 8 | Berlin | Germany | 10435 | ||
| 9 | Berlin | Germany | 12161 | ||
| 10 | Berlin | Germany | 12435 | ||
| 11 | Berlin | Germany | 13055 | ||
| 12 | Berlin | Germany | 13125 | ||
| 13 | Berlin | Germany | 14129 | ||
| 14 | Blaubeuren | Germany | 89143 | ||
| 15 | Bonn | Germany | 53111 | ||
| 16 | Bruchhausen-Vilsen | Germany | 27305 | ||
| 17 | Chemnitz | Germany | 09130 | ||
| 18 | Donaueschingen | Germany | 78166 | ||
| 19 | Dresden | Germany | 01067 | ||
| 20 | Dresden | Germany | 01097 | ||
| 21 | Dresden | Germany | 01109 | ||
| 22 | Dresden | Germany | 01307 | ||
| 23 | Düsseldorf | Germany | 40217 | ||
| 24 | Düsseldorf | Germany | 40225 | ||
| 25 | Erfurt | Germany | 99096 | ||
| 26 | Essen | Germany | 45239 | ||
| 27 | Frankfurt Am Main | Germany | 60590 | ||
| 28 | Freiburg | Germany | 79106 | ||
| 29 | Giessen | Germany | 35392 | ||
| 30 | Gommern | Germany | 39245 | ||
| 31 | Goslar | Germany | 38642 | ||
| 32 | Greifswald | Germany | 17475 | ||
| 33 | Göttingen | Germany | 37075 | ||
| 34 | Halle | Germany | 06108 | ||
| 35 | Halle | Germany | 06120 | ||
| 36 | Halle | Germany | 06128 | ||
| 37 | Hamburg | Germany | 20246 | ||
| 38 | Hamburg | Germany | 22147 | ||
| 39 | Hamburg | Germany | 22767 | ||
| 40 | Hannover | Germany | 30625 | ||
| 41 | Heidelberg | Germany | 69120 | ||
| 42 | Heidelberg | Germany | 69121 | ||
| 43 | Herne | Germany | 44652 | ||
| 44 | Hildesheim | Germany | 31134 | ||
| 45 | Hofheim | Germany | 65719 | ||
| 46 | Jena | Germany | 07747 | ||
| 47 | Kiel | Germany | 24105 | ||
| 48 | Köln | Germany | 50679 | ||
| 49 | Köln | Germany | 50924 | ||
| 50 | Köln | Germany | 51149 | ||
| 51 | Leipzig | Germany | 04103 | ||
| 52 | Leipzig | Germany | 04109 | ||
| 53 | Lingen | Germany | 49808 | ||
| 54 | Ludwigsfelde | Germany | 14974 | ||
| 55 | Mainz | Germany | 55131 | ||
| 56 | Muenchen | Germany | 80336 | ||
| 57 | Mönchengladbach | Germany | 41061 | ||
| 58 | München | Germany | 80335 | ||
| 59 | München | Germany | 81541 | ||
| 60 | Naumburg | Germany | 06628 | ||
| 61 | Naunhof | Germany | 04683 | ||
| 62 | Neuss | Germany | 41460 | ||
| 63 | Neuss | Germany | 41462 | ||
| 64 | Nienburg | Germany | 31582 | ||
| 65 | Olsberg | Germany | 59939 | ||
| 66 | Osnabrück | Germany | 49074 | ||
| 67 | Plochingen | Germany | 73207 | ||
| 68 | Potsdam | Germany | 14469 | ||
| 69 | Ratingen | Germany | 40882 | ||
| 70 | Regensburg | Germany | 93053 | ||
| 71 | Rendsburg | Germany | 24768 | ||
| 72 | Rheine | Germany | 48431 | ||
| 73 | Rostock | Germany | 18059 | ||
| 74 | Saarbruecken | Germany | 66111 | ||
| 75 | Sendenhorst | Germany | 48324 | ||
| 76 | Stuttgart | Germany | 70178 | ||
| 77 | Stuttgart | Germany | 70372 | ||
| 78 | Traunstein | Germany | 83278 | ||
| 79 | Trier | Germany | 54292 | ||
| 80 | Tübingen | Germany | 72076 | ||
| 81 | Ulm | Germany | 89081 | ||
| 82 | Wiesbaden | Germany | 65189 | ||
| 83 | Wuerzburg | Germany | 97080 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01332994
Other Study ID Numbers:
- ML22985
First Posted:
Apr 11, 2011
Last Update Posted:
Sep 7, 2015
Last Verified:
Aug 1, 2015
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | After a screening period of up to 4 weeks, eligible participants were treated according to a predefined treatment algorithm based on disease response. In certain cases a re-screening was allowed. Participants were enrolled into the study with the administration of their first dose. |
| Arm/Group Title | Tocilizumab (TCZ)/TCZ or TCZ/Rituximab (RTX) |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using Disease Activity Score Based on 28-Joint Count (DAS28) to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of less than (<) 2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score greater than (>) 1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score less than or equal to (≤) 1.2 or a score >3.2, received RTX 1000 milligrams (mg) via IV infusion at Weeks 16 and 18. |
| Period Title: Overall Study | |
| STARTED | 519 |
| Completed Week 16 | 463 |
| Completed Week 32 (TCZ/TCZ) | 200 |
| Completed Week 32 (TCZ/RTX) | 26 |
| Completed Week 66 (TCZ/RTX) | 25 |
| COMPLETED | 448 |
| NOT COMPLETED | 71 |
Baseline Characteristics
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Overall Participants | 519 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
55.7
(11.9)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
352
67.8%
|
| Male |
167
32.2%
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 519 |
| Number (95% Confidence Interval) [percentage of participants] |
42.8
8.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1648 |
| Comments | Exact one-sided binomial test on single proportions with a significance level of alpha equals (=) 0.025. Null hypothesis: Proportion of participants reaching DAS28 remission (<2.6) at Week 16 is ≤45 percent (%). | |
| Method | Exact one-sided binomial test | |
| Comments | ||
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 519 |
| Week 4 |
21.6
4.2%
|
| Week 8 |
40.1
7.7%
|
| Week 12 |
43.2
8.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population: All participants who received at least one dose of TCZ in the first treatment period with at least one efficacy measurement under TCZ, receiving TCZ in the second treatment period. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 213 |
| Week 16 |
1.4
0.3%
|
| Week 20 |
41.3
8%
|
| Week 24 |
51.2
9.9%
|
| Week 28 |
55.9
10.8%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 213 |
| Number (95% Confidence Interval) [percentage of participants] |
54.9
10.6%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 27 |
| Number (95% Confidence Interval) [percentage of participants] |
14.8
2.9%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 519 |
| Number (95% Confidence Interval) [percentage of participants] |
68.8
13.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 27 |
| Number (95% Confidence Interval) [percentage of participants] |
33.3
6.4%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 519 |
| Number (95% Confidence Interval) [percentage of participants] |
86.1
16.6%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 519 |
| Week 4 |
74.6
14.4%
|
| Week 8 |
81.5
15.7%
|
| Week 12 |
83.4
16.1%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population: All participants who received at least one dose of TCZ in the first treatment period and at least one dose of RTX in the second treatment period with at least one efficacy measurement under RTX. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 27 |
| Number (95% Confidence Interval) [percentage of participants] |
37.0
7.1%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 516 |
| Baseline (n=516) |
5.7
(1.0)
|
| Week 4 (n=508) |
3.6
(1.3)
|
| Week 8 (n=491) |
3.0
(1.4)
|
| Week 12 (n=483) |
2.8
(1.4)
|
| Week 16 (n=485) |
2.6
(1.3)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 213 |
| Baseline (n=213) |
6.0
(0.9)
|
| Week 4 (n=213) |
4.0
(1.2)
|
| Week 8 (n=205) |
3.4
(1.2)
|
| Week 12 (n=207) |
3.3
(1.1)
|
| Week 16 (n=213) |
3.3
(0.6)
|
| Week 20 (n=206) |
2.8
(1.0)
|
| Week 24 (n=197) |
2.6
(1.1)
|
| Week 28 (n=200) |
2.4
(1.1)
|
| Week 32 (n=193) |
2.5
(1.2)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 27 |
| Baseline (n=27) |
5.7
(1.0)
|
| Week 4 (n=27) |
4.5
(1.2)
|
| Week 8 (n=26) |
4.2
(1.5)
|
| Week 12 (n=27) |
4.8
(1.6)
|
| Week 16 (n=27) |
5.1
(1.2)
|
| Week 24 (n=26) |
4.6
(1.4)
|
| Week 32 (n=26) |
4.0
(1.5)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 26 |
| Week 40 (n=26) |
3.9
(1.5)
|
| Week 48 (n=25) |
3.9
(1.2)
|
| Week 56 (n=22) |
4.1
(1.8)
|
| Week 66 (n=25) |
3.9
(1.5)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 519 |
| Week 4, Good |
36.0
6.9%
|
| Week 4, Moderate |
47.8
9.2%
|
| Week 4, None |
16.2
3.1%
|
| Week 8, Good |
56.1
10.8%
|
| Week 8, Moderate |
30.6
5.9%
|
| Week 8, None |
13.3
2.6%
|
| Week 12, Good |
61.1
11.8%
|
| Week 12, Moderate |
25.6
4.9%
|
| Week 12, None |
13.3
2.6%
|
| Week 16, Good |
68.2
13.1%
|
| Week 16, Moderate |
20.2
3.9%
|
| Week 16, None |
11.6
2.2%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 27 |
| Good |
25.9
5%
|
| Moderate |
29.6
5.7%
|
| None |
44.4
8.6%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 213 |
| Week 20, Good |
65.3
12.6%
|
| Week 20, Moderate |
30.0
5.8%
|
| Week 20, None |
4.7
0.9%
|
| Week 24, Good |
68.1
13.1%
|
| Week 24, Moderate |
23.9
4.6%
|
| Week 24, None |
8.0
1.5%
|
| Week 28, Good |
72.8
14%
|
| Week 28, Moderate |
19.2
3.7%
|
| Week 28, None |
8.0
1.5%
|
| Week 32, Good |
66.7
12.9%
|
| Week 32, Moderate |
20.7
4%
|
| Week 32, None |
12.7
2.4%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 519 |
| Week 4, ACR20 |
39.1
7.5%
|
| Week 4, ACR50 |
15.0
2.9%
|
| Week 4, ACR70 |
5.8
1.1%
|
| Week 8, ACR20 |
61.1
11.8%
|
| Week 8, ACR50 |
33.5
6.5%
|
| Week 8, ACR70 |
15.2
2.9%
|
| Week 12, ACR20 |
64.0
12.3%
|
| Week 12, ACR50 |
42.8
8.2%
|
| Week 12, ACR70 |
20.2
3.9%
|
| Week 16, ACR20 |
67.1
12.9%
|
| Week 16, ACR50 |
45.7
8.8%
|
| Week 16, ACR70 |
24.5
4.7%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 27 |
| ACR20 |
40.7
7.8%
|
| ACR50 |
33.3
6.4%
|
| ACR70 |
22.2
4.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 213 |
| Week 20, ACR20 |
74.2
14.3%
|
| Week 20, ACR50 |
45.1
8.7%
|
| Week 20, ACR70 |
21.1
4.1%
|
| Week 24, ACR20 |
72.8
14%
|
| Week 24, ACR50 |
49.8
9.6%
|
| Week 24, ACR70 |
21.6
4.2%
|
| Week 28, ACR20 |
73.2
14.1%
|
| Week 28, ACR50 |
53.1
10.2%
|
| Week 28, ACR70 |
30.5
5.9%
|
| Week 32, ACR20 |
75.6
14.6%
|
| Week 32, ACR50 |
54.9
10.6%
|
| Week 32, ACR70 |
34.3
6.6%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 509 |
| CDAI, Week 4 (n=509) |
-10.9
(10.2)
|
| CDAI, Week 8 (n=497) |
-16.5
(11.1)
|
| CDAI, Week 12 (n=486) |
-18.3
(11.5)
|
| CDAI, Week 16 (n=485) |
-19.4
(11.5)
|
| SDAI, Week 4 (n=496) |
-12.3
(10.6)
|
| SDAI, Week 8 (n=489) |
-17.9
(11.5)
|
| SDAI, Week 12 (n=474) |
-19.7
(11.9)
|
| SDAI, Week 16 (n=471) |
-20.7
(12.2)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 25 |
| CDAI (n=25) |
-14.2
(12.0)
|
| SDAI (n=24) |
-14.0
(12.5)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 208 |
| CDAI, Week 20 (n=208) |
-21.7
(11.7)
|
| CDAI, Week 24 (n=199) |
-22.8
(11.4)
|
| CDAI, Week 28 (n=200) |
-24.6
(12.5)
|
| CDAI, Week 32 (n=194) |
-24.0
(13.4)
|
| SDAI, Week 20 (n=200) |
-22.9
(12.5)
|
| SDAI, Week 24 (n=190) |
-24.3
(12.1)
|
| SDAI, Week 28 (n=195) |
-25.9
(13.2)
|
| SDAI, Week 32 (n=189) |
-25.2
(14.0)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 509 |
| Week 4 (n=509) |
4.9
(7.2)
|
| Week 8 (n=496) |
6.4
(8.8)
|
| Week 12 (n=483) |
6.9
(9.1)
|
| Week 16 (n=477) |
7.5
(9.1)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 497 |
| Week 4 (n=497) |
-1.4
(1.9)
|
| Week 8 (n=492) |
-1.4
(1.9)
|
| Week 12 (n=476) |
-1.4
(1.9)
|
| Week 16 (n=471) |
-1.3
(1.9)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 507 |
| Week 4 (n=507) |
-25.2
(18.1)
|
| Week 8 (n=494) |
-26.6
(18.9)
|
| Week 12 (n=484) |
-26.3
(19.1)
|
| Week 16 (n=484) |
-27.5
(18.7)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population. Participants with evaluable data at the designated visit were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 26 |
| Mean (Standard Deviation) [g/L] |
-2.0
(8.3)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population. Participants with evaluable data at the designated visit were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 25 |
| Mean (Standard Deviation) [mg/dL] |
0.7
(1.7)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population. Participants with evaluable data at the designated visit were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 26 |
| Mean (Standard Deviation) [mm/h] |
11.5
(17.9)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 207 |
| Week 20 (n=207) |
5.5
(9.0)
|
| Week 24 (n=198) |
6.6
(9.4)
|
| Week 28 (n=197) |
6.9
(9.5)
|
| Week 32 (n=197) |
8.3
(10.4)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 200 |
| Week 20 (n=200) |
-1.3
(1.9)
|
| Week 24 (n=191) |
-1.4
(1.9)
|
| Week 28 (n=195) |
-1.3
(1.9)
|
| Week 32 (n=192) |
-1.3
(1.9)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 206 |
| Week 20 (n=206) |
-28.6
(17.6)
|
| Week 24 (n=197) |
-29.4
(18.0)
|
| Week 28 (n=200) |
-29.4
(18.1)
|
| Week 32 (n=196) |
-28.6
(20.2)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants who withdrew for reasons other than insufficient therapeutic response were not included in the analysis. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 485 |
| Number (95% Confidence Interval) [percentage of participants] |
0.2
0%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT1 Population: All participants who received at least one dose of TCZ in the first treatment period and who completed the study reaching remission at Week 16. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 196 |
| Naive B-cell compartment (n=196) |
61.1
|
| Transitional B-cells (n=196) |
1.4
|
| Naive B-cells (n=196) |
58.1
|
| Memory including double-negative (n=46) |
56.4
|
| Memory excluding double-negative (n=194) |
46.5
|
| Pre-switch memory B-cells (n=196) |
11.1
|
| Post-switch memory B-cells (n=196) |
16.4
|
| IgG-positive class-switched B-cells (n=195) |
9.9
|
| IgA-positive class-switched B-cells (n=194) |
7.4
|
| Double-negative B-cells (n=46) |
6.1
|
| Plasmablasts (n=196) |
0.3
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 197 |
| Naive B-cell compartment (n=197) |
57.1
|
| Transitional B-cells (n=197) |
1.3
|
| Naive B-cells (n=197) |
55.5
|
| Memory including double-negative (n=57) |
63.2
|
| Memory excluding double-negative (n=196) |
49.7
|
| Pre-switch memory B-cells (n=197) |
11.6
|
| Post-switch memory B-cells (n=197) |
17.2
|
| IgG-positive class-switched B-cells (n=196) |
10
|
| IgA-positive class-switched B-cells (n=196) |
8.0
|
| Double-negative B-cells (n=57) |
6.6
|
| Plasmablasts (n=197) |
0.3
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 25 |
| Naive B-cell compartment (n=25) |
65.9
|
| Transitional B-cells (n=25) |
1.6
|
| Naive B-cells (n=25) |
61.9
|
| Memory including double-negative (n=4) |
45.1
|
| Memory excluding double-negative (n=25) |
41.5
|
| Pre-switch memory B-cells (n=25) |
9.1
|
| Post-switch memory B-cells (n=25) |
16.1
|
| IgG-positive class-switched B-cells (n=25) |
8.7
|
| IgA-positive class-switched B-cells (n=25) |
7.7
|
| Double-negative B-cells (n=4) |
7.5
|
| Plasmablasts (n=25) |
0.3
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT1 Population; n = number of data pairs included in the analysis. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 217 |
| Measure Pairs | 192 |
| Naive B-cell compartment (n=192) |
-0.02258
|
| Transitional B-cells (n=192) |
-0.00949
|
| Naive B-cells (n=192) |
-0.01920
|
| Memory B-cells (n=62) |
-0.03148
|
| Pre-switch memory B-cells (n=192) |
0.03221
|
| Post-switch memory B-cells (n=192) |
0.05419
|
| IgG-positive class-switched B-cells (n=192) |
0.08864
|
| IgA-positive class-switched B-cells (n=192) |
0.01041
|
| Double-negative B-cells (n=62) |
-0.02134
|
| Plasmablasts (n=192) |
0.00397
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Naive B-cell compartment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7559 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Transitional B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8961 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Naive B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7915 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8081 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Pre-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6574 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Post-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4553 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | IgG-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2215 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | IgA-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8860 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Double-negative B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8693 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Plasmablasts | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9564 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population; n = number of data pairs included in the analysis. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 213 |
| Measure Pairs | 199 |
| Week 16, Naive B-cell compartment (n=199) |
0.00007
|
| Week 16, Transitional B-cells (n=199) |
-0.06529
|
| Week 16, Naive B-cells (n=199) |
0.02334
|
| Week 16, Memory B-cells (n=75) |
0.03478
|
| Week 16, Pre-switch memory B-cells (n=199) |
-0.01889
|
| Week 16, Post-switch memory B-cells (n=199) |
-0.04161
|
| Week 16, IgG-positive class-switched (n=199) |
-0.06235
|
| Week 16, IgA-positive class-switched (n=199) |
-0.06492
|
| Week 16, Double-negative B-cells (n=75) |
-0.04352
|
| Week 16, Plasmablasts (n=199) |
-0.13161
|
| Week 24, Naive B-cell compartment (n=162) |
-0.18469
|
| Week 24, Transitional B-cells (n=162) |
-0.21966
|
| Week 24, Naive B-cells (n=162) |
-0.15683
|
| Week 24, Memory B-cells (n=76) |
0.15135
|
| Week 24, Pre-switch memory B-cells (n=162) |
0.08074
|
| Week 24, Post-switch memory B-cells (n=162) |
0.10798
|
| Week 24, IgG-positive class-switched (n=161) |
0.10752
|
| Week 24, IgA-positive class-switched (n=162) |
0.11023
|
| Week 24, Double-negative B-cells (n=76) |
0.05609
|
| Week 24, Plasmablasts (n=162) |
0.07468
|
| Week 32, Naive B-cell compartment (n=179) |
-0.12635
|
| Week 32, Transitional B-cells (n=179) |
-0.09234
|
| Week 32, Naive B-cells (n=179) |
-0.11114
|
| Week 32, Memory B-cells (n=88) |
0.05361
|
| Week 32, Pre-switch memory B-cells (n=179) |
0.12265
|
| Week 32, Post-switch memory B-cells (n=179) |
0.05867
|
| Week 32, IgG-positive class-switched (n=181) |
0.06381
|
| Week 32, IgA-positive class-switched (n=181) |
0.06036
|
| Week 32, Double-negative B-cells (n=90) |
-0.06310
|
| Week 32, Plasmablasts (n=179) |
0.02205
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Naive B-cell compartment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9993 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Transitional B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3596 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Naive B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7435 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7671 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Pre-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7912 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Post-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5595 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, IgG-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3817 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, IgA-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3623 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Double-negative B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7108 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Plasmablasts | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0639 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 24, Naive B-cell compartment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0186 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 24, Transitional B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0050 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 24, Naive B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0463 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 24, Memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1919 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 24, Pre-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3071 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 24, Post-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1714 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 24, IgG-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1746 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 24, IgA-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1626 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 24, Double-negative B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6304 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 24, Plasmablasts | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3449 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 32, Naive B-cell compartment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0919 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 32, Transitional B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2189 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 32, Naive B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1386 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 32, Memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6199 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 32, Pre-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1019 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 32, Post-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4353 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 32, IgG-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3934 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 32, IgA-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4196 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 32, Double-negative B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5546 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 32, Plasmablasts | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7695 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population; n = number of data pairs included in the analysis. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 27 |
| Measure Pairs | 24 |
| Week 16, Naive B-cell compartment (n=24) |
0.09611
|
| Week 16, Transitional B-cells (n=24) |
0.08571
|
| Week 16, Naive B-cells (n=24) |
0.00870
|
| Week 16, Memory B-cells (n=6) |
-0.60000
|
| Week 16, Pre-switch memory B-cells (n=24) |
-0.15217
|
| Week 16, Post-switch memory B-cells (n=24) |
-0.04004
|
| Week 16, IgG-positive class-switched (n=24) |
-0.07528
|
| Week 16, IgA-positive class-switched (n=24) |
0.27049
|
| Week 16, Double-negative B-cells (n=6) |
-0.14286
|
| Week 16, Plasmablasts (n=24) |
0.13232
|
| Week 32, Naive B-cell compartment (n=0) |
NA
|
| Week 32, Transitional B-cells (n=0) |
NA
|
| Week 32, Naive B-cells (n=0) |
NA
|
| Week 32, Memory B-cells (n=0) |
NA
|
| Week 32, Pre-switch memory B-cells (n=0) |
NA
|
| Week 32, Post-switch memory B-cells (n=0) |
NA
|
| Week 32, IgG-positive class-switched (n=0) |
NA
|
| Week 32, IgA-positive class-switched (n=0) |
NA
|
| Week 32, Double-negative B-cells (n=0) |
NA
|
| Week 32, Plasmablasts (n=0) |
NA
|
| Week 40, Naive B-cell compartment (n=2) |
1.00000
|
| Week 40, Transitional B-cells (n=2) |
-1.00000
|
| Week 40, Naive B-cells (n=2) |
1.00000
|
| Week 40, Memory B-cells (n=0) |
NA
|
| Week 40, Pre-switch memory B-cells (n=2) |
1.00000
|
| Week 40, Post-switch memory B-cells (n=2) |
1.00000
|
| Week 40, IgG-positive class-switched (n=2) |
1.00000
|
| Week 40, IgA-positive class-switched (n=2) |
1.00000
|
| Week 40, Double-negative B-cells (n=0) |
NA
|
| Week 40, Plasmablasts (n=2) |
1.00000
|
| Week 48, Naive B-cell compartment (n=5) |
0.30000
|
| Week 48, Transitional B-cells (n=5) |
-0.60000
|
| Week 48, Naive B-cells (n=5) |
0.30000
|
| Week 48, Memory B-cells (n=1) |
NA
|
| Week 48, Pre-switch memory B-cells (n=5) |
0.60000
|
| Week 48, Post-switch memory B-cells (n=5) |
0.20000
|
| Week 48, IgG-positive class-switched (n=5) |
0.20000
|
| Week 48, IgA-positive class-switched (n=5) |
0.50000
|
| Week 48, Double-negative B-cells (n=1) |
NA
|
| Week 48, Plasmablasts (n=5) |
0.10000
|
| Week 66, Naive B-cell compartment (n=10) |
0.12727
|
| Week 66, Transitional B-cells (n=10) |
-0.03030
|
| Week 66, Naive B-cells (n=10) |
0.04242
|
| Week 66, Memory B-cells (n=3) |
1.00000
|
| Week 66, Pre-switch memory B-cells (n=10) |
-0.03030
|
| Week 66, Post-switch memory B-cells (n=10) |
0.16364
|
| Week 66, IgG-positive class-switched (n=10) |
0.07295
|
| Week 66, IgA-positive class-switched (n=10) |
0.12805
|
| Week 66, Double-negative B-cells (n=3) |
1.00000
|
| Week 66, Plasmablasts (n=10) |
0.30909
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Naive B-cell compartment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6551 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Transitional B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6905 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Naive B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9678 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2080 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Pre-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4778 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Post-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8526 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, IgG-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7266 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, IgA-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2011 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Double-negative B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7872 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 16, Plasmablasts | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5377 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 48, Naive B-cell compartment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6238 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 48, Transitional B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2848 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 48, Naive B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6238 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 48, Pre-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2848 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 48, Post-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7471 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 48, IgG-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7471 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 48, IgA-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3910 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 48, Plasmablasts | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8729 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 66, Naive B-cell compartment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7261 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 66, Transitional B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9338 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 66, Naive B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9074 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 66, Memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 66, Pre-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9338 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 66, Post-switch memory B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6515 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 66, IgG-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8413 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 66, IgA-positive class-switched B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7244 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 66, Double-negative B-cells | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | TCZ/TCZ or TCZ/RTX |
|---|---|---|
| Comments | Week 66, Plasmablasts | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3848 |
| Comments | ||
| Method | Spearman Rank-Order Correlation | |
| Comments | Probability values for the Spearman correlation were calculated as [square root of (n minus 2) x [square root of (r^2 divided by 1 minus r^2)]. | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Employed participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 241 |
| Due to RA, Baseline (n=241) |
1.03
(2.30)
|
| Due to RA, Week 16 (n=221) |
0.39
(1.51)
|
| Due to other reasons, Baseline (n=233) |
0.14
(0.87)
|
| Due to other reasons, Week 16 (n=222) |
0.32
(1.26)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 513 |
| Physical functioning, Baseline (n=511) |
49.6
(23.7)
|
| Physical functioning, Week 16 (n=473) |
64.1
(25.5)
|
| Role (physical), Baseline (n=508) |
12.9
(18.1)
|
| Role (physical), Week 16 (n=472) |
29.9
(21.4)
|
| Bodily pain, Baseline (n=512) |
31.3
(18.2)
|
| Bodily pain, Week 16 (n=474) |
55.3
(17.8)
|
| General health, Baseline (n=504) |
43.6
(16.7)
|
| General health, Week 16 (n=468) |
54.3
(18.3)
|
| Vitality, Baseline (n=512) |
44.0
(19.7)
|
| Vitality, Week 16 (n=474) |
58.1
(20.4)
|
| Social functioning, Baseline (n=507) |
68.1
(24.8)
|
| Social functioning, Week 16 (n=464) |
80.1
(21.6)
|
| Role (emotional), Baseline (n=505) |
55.9
(45.0)
|
| Role (emotional), Week 16 (n=472) |
70.9
(42.1)
|
| Mental health, Baseline (n=513) |
63.5
(18.7)
|
| Mental health, Week 16 (n=474) |
72.3
(17.9)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 470 |
| Physical functioning (n=466) |
14.3
(21.8)
|
| Role (physical) (n=461) |
17.0
(22.0)
|
| Bodily pain (n=470) |
23.9
(21.1)
|
| General health (n=454) |
10.4
(18.5)
|
| Vitality (n=468) |
13.9
(19.3)
|
| Social functioning (n=456) |
12.0
(23.8)
|
| Role (emotional) (n=459) |
14.7
(46.1)
|
| Mental health (n=468) |
8.7
(16.8)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 188 |
| Physical functioning (n=188) |
3.6
(16.6)
|
| Role (physical) (n=187) |
2.0
(20.6)
|
| Bodily pain (n=188) |
3.2
(16.5)
|
| General health (n=184) |
2.6
(14.3)
|
| Vitality (n=186) |
2.7
(14.2)
|
| Social functioning (n=184) |
-0.3
(19.6)
|
| Role (emotional) (n=184) |
5.5
(42.3)
|
| Mental health (n=186) |
0.7
(15.3)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 26 |
| Physical functioning (n=26) |
2.5
(20.0)
|
| Role (physical) (n=24) |
-1.0
(21.5)
|
| Bodily pain (n=26) |
10.6
(20.8)
|
| General health (n=24) |
5.2
(18.1)
|
| Vitality (n=26) |
1.0
(9.3)
|
| Social functioning (n=24) |
-3.1
(17.4)
|
| Role (emotional) (n=24) |
2.8
(35.3)
|
| Mental health (n=26) |
3.4
(10.7)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 513 |
| Baseline (n=513) |
1.24
(0.67)
|
| Week 16 (n=472) |
0.75
(0.67)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants with evaluable data at the designated visit were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 466 |
| Mean (Standard Deviation) [units on a scale] |
-0.48
(0.58)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population. Participants with evaluable data at the designated visit were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 187 |
| Mean (Standard Deviation) [units on a scale] |
-0.06
(0.34)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population. Participants with evaluable data at the designated visit were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 26 |
| Mean (Standard Deviation) [units on a scale] |
-0.10
(0.39)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 519 |
| Number [percentage of participants] |
61.1
11.8%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 510 |
| FACIT-F TOI, Baseline (n=498) |
66.2
(20.6)
|
| FACIT-F TOI, Week 16 (n=460) |
80.8
(19.3)
|
| FACIT-G total, Baseline (n=498) |
71.1
(15.7)
|
| FACIT-G total, Week 16 (n=462) |
82.6
(15.9)
|
| FACIT-F total, Baseline (n=494) |
103.8
(25.5)
|
| FACIT-F total, Week 16 (n=458) |
121.9
(25.3)
|
| FACIT-F fatigue, Baseline (n=510) |
32.7
(11.6)
|
| FACIT-F fatigue, Week 16 (n=475) |
39.2
(10.6)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 467 |
| FACIT-F TOI (n=445) |
14.2
(17.9)
|
| FACIT-G total (n=445) |
10.8
(13.6)
|
| FACIT-F total (n=439) |
17.5
(21.8)
|
| FACIT-F fatigue (n=467) |
6.6
(9.9)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 186 |
| FACIT-F TOI (n=172) |
1.7
(12.9)
|
| FACIT-G total (n=174) |
1.1
(9.2)
|
| FACIT-F total (n=170) |
2.0
(15.1)
|
| FACIT-F fatigue (n=186) |
0.8
(7.4)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT3 Population. Participants with evaluable data at the designated visit were included. |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX |
|---|---|
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. |
| Measure Participants | 26 |
| FACIT-F TOI |
2.9
(9.8)
|
| FACIT-G total |
3.0
(8.3)
|
| FACIT-F total |
4.4
(12.5)
|
| FACIT-F fatigue |
1.4
(5.8)
|
Adverse Events
| Time Frame | Up to 66 weeks | |
|---|---|---|
| Adverse Event Reporting Description | Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX). | |
| Arm/Group Title | TCZ/TCZ or TCZ/RTX | |
| Arm/Group Description | All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18. | |
All Cause Mortality |
||
| TCZ/TCZ or TCZ/RTX | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| TCZ/TCZ or TCZ/RTX | ||
| Affected / at Risk (%) | # Events | |
| Total | 54/519 (10.4%) | |
| Blood and lymphatic system disorders | ||
| Leukopenia | 1/519 (0.2%) | |
| Neutropenia | 1/519 (0.2%) | |
| Thrombocytopenia | 1/519 (0.2%) | |
| Cardiac disorders | ||
| Acute myocardial infarction | 1/519 (0.2%) | |
| Atrial fibrillation | 1/519 (0.2%) | |
| Atrioventricular block complete | 1/519 (0.2%) | |
| Coronary artery disease | 1/519 (0.2%) | |
| Myocardial infarction | 1/519 (0.2%) | |
| Gastrointestinal disorders | ||
| Abdominal pain | 2/519 (0.4%) | |
| Abdominal pain lower | 1/519 (0.2%) | |
| Diarrhoea | 1/519 (0.2%) | |
| Gastrointestinal perforation | 1/519 (0.2%) | |
| Gastrooesophageal reflux disease | 1/519 (0.2%) | |
| General disorders | ||
| Fatigue | 1/519 (0.2%) | |
| Oedema peripheral | 1/519 (0.2%) | |
| Immune system disorders | ||
| Hypersensitivity | 2/519 (0.4%) | |
| Infections and infestations | ||
| Bronchitis | 3/519 (0.6%) | |
| Diverticulitis | 2/519 (0.4%) | |
| Pneumonia | 2/519 (0.4%) | |
| Abscess limb | 1/519 (0.2%) | |
| Anal abscess | 1/519 (0.2%) | |
| Gangrene | 1/519 (0.2%) | |
| Infection | 1/519 (0.2%) | |
| Localised infection | 1/519 (0.2%) | |
| Lower respiratory tract infection bacterial | 1/519 (0.2%) | |
| Respiratory tract infection | 1/519 (0.2%) | |
| Tonsillitis | 1/519 (0.2%) | |
| Wound infection | 1/519 (0.2%) | |
| Injury, poisoning and procedural complications | ||
| Fall | 2/519 (0.4%) | |
| Contusion | 1/519 (0.2%) | |
| Craniocerebral injury | 1/519 (0.2%) | |
| Infusion related reaction | 1/519 (0.2%) | |
| Joint dislocation | 1/519 (0.2%) | |
| Overdose | 1/519 (0.2%) | |
| Road traffic accident | 1/519 (0.2%) | |
| Tendon rupture | 1/519 (0.2%) | |
| Thoracic vertebral fracture | 1/519 (0.2%) | |
| Wound | 1/519 (0.2%) | |
| Hip fracture | 1/519 (0.2%) | |
| Lower limb fracture | 1/519 (0.2%) | |
| Investigations | ||
| Alanine aminotransferase increased | 1/519 (0.2%) | |
| Fibrin D dimer increased | 1/519 (0.2%) | |
| Liver function test abnormal | 1/519 (0.2%) | |
| Musculoskeletal and connective tissue disorders | ||
| Bursitis | 3/519 (0.6%) | |
| Rheumatoid arthritis | 2/519 (0.4%) | |
| Joint destruction | 1/519 (0.2%) | |
| Musculoskeletal chest pain | 1/519 (0.2%) | |
| Osteoarthritis | 1/519 (0.2%) | |
| Sacroiliitis | 1/519 (0.2%) | |
| Spinal column stenosis | 1/519 (0.2%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Laryngeal squamous cell carcinoma | 1/519 (0.2%) | |
| Malignant melanoma | 1/519 (0.2%) | |
| Nervous system disorders | ||
| Dizziness | 1/519 (0.2%) | |
| Intracranial haematoma | 1/519 (0.2%) | |
| Migraine | 1/519 (0.2%) | |
| Renal and urinary disorders | ||
| Haematuria | 1/519 (0.2%) | |
| Nephrolithiasis | 1/519 (0.2%) | |
| Urinary retention | 1/519 (0.2%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Allergic cough | 1/519 (0.2%) | |
| Asthma | 1/519 (0.2%) | |
| Hyperventilation | 1/519 (0.2%) | |
| Vascular disorders | ||
| Haematoma | 1/519 (0.2%) | |
| Hypertension | 1/519 (0.2%) | |
| Hypertensive crisis | 1/519 (0.2%) | |
Other (Not Including Serious) Adverse Events |
||
| TCZ/TCZ or TCZ/RTX | ||
| Affected / at Risk (%) | # Events | |
| Total | 104/519 (20%) | |
| Infections and infestations | ||
| Nasopharyngitis | 77/519 (14.8%) | |
| Vascular disorders | ||
| Hypertension | 30/519 (5.8%) | |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-LaRoche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01332994
Other Study ID Numbers:
- ML22985
First Posted:
Apr 11, 2011
Last Update Posted:
Sep 7, 2015
Last Verified:
Aug 1, 2015