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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
519
1 g intravenously at Week 16 and 18
8 mg/kg intravenously every 4 weeks for 12 weeks.
8 mg/kg intravenously every 4 weeks from Week 16 to Week 28
Unnamed facility
Aachen, Germany
Unnamed facility
Bad Aibling, Germany
Unnamed facility
Bad Bramstedt, Germany
Unnamed facility
Bad Nauheim, Germany
Unnamed facility
Bad Staffelstein, Germany
Unnamed facility
Bayreuth, Germany
Percentage of Participants Achieving Remission at Week 16 According to DAS28
The DAS28 was calculated as \[0.28 times (x) the square root of number of swollen joints\] plus (+) \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of erythrocyte sedimentation rate (ESR)\] + \[0.014 x Visual Analog Scale (VAS) patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score \<2.6 at the assessment visit.
Time frame: Week 16
Percentage of Participants Achieving Remission According to DAS28 at Weeks 4, 8, and 12
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score \<2.6 at the assessment visit.
Time frame: Weeks 4, 8, and 12
Percentage of Participants Achieving Remission According to DAS28 at Weeks 16, 20, 24, and 28 Among Participants Treated With 8 Courses of Tocilizumab
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score \<2.6 at the assessment visit.
Time frame: Weeks 16, 20, 24, and 28
Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Participants Treated With 8 Courses of Tocilizumab
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score \<2.6 at the assessment visit.
Time frame: Week 32
Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Nonresponding Participants Treated With Rituximab
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score \<2.6 at the assessment visit.
Time frame: Week 32
Percentage of Participants Achieving Low Disease Activity Score (LDAS) According to DAS28
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x the patient global assessment of disease activity using a VAS\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. LDAS was defined as a DAS28 score \<3.2 at the assessment visit.
Time frame: Week 16
Percentage of Participants Achieving LDAS According to DAS28 Among Among Nonresponding Participants Treated With Rituximab
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x the patient global assessment of disease activity using a VAS\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. LDAS was defined as a DAS28 score \<3.2 at the assessment visit.
Time frame: Week 32
Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Week 16
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions \>1.2 points from Baseline to the assessment visit were considered clinically relevant.
Time frame: Baseline and Week 16
Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Weeks 4, 8, and 12
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions \>1.2 points from Baseline to the assessment visit were considered clinically relevant.
Time frame: Baseline and Weeks 4, 8, and 12
Percentage of Participants Achieving a Clinically Relevant Reduction in DAS28 From Week 16 to Week 32 Among Nonresponding Participants Treated With Rituximab
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions \>1.2 points from the reference visit (Week 16) to the assessment visit were considered clinically relevant.
Time frame: Weeks 16 and 32
DAS28 Scores During and After Treatment
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
Time frame: Baseline and Weeks 4, 8, 12, 16
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, and 32
DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
Time frame: Baseline and Weeks 4, 8, 12, 16, 24, and 32
DAS28 Scores During Safety Follow-Up Among Nonresponding Participants Treated With Rituximab
The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
Time frame: Weeks 40, 48, 56, and 66
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from Baseline. Participants with a score ≤3.2 and reduction of \>1.2 points were assessed as having a 'good' response. Participants with a score \>3.2 with reduction of \>1.2 points, or a score ≤5.1 with reduction of \>0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score \>5.1 with reduction of \>0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
Time frame: Baseline and Weeks 4, 8, 12, and 16
Percentage of Participants Achieving a Response According to EULAR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit (Week 16). Participants with a score ≤3.2 and reduction of \>1.2 points were assessed as having a 'good' response. Participants with a score \>3.2 with reduction of \>1.2 points, or a score ≤5.1 with reduction of \>0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score \>5.1 with reduction of \>0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
Time frame: Weeks 16 and 32
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from Baseline. Participants with a score ≤3.2 and reduction of \>1.2 points were assessed as having a 'good' response. Participants with a score \>3.2 with reduction of \>1.2 points, or a score ≤5.1 with reduction of \>0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score \>5.1 with reduction of \>0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
Time frame: Baseline and Weeks 20, 24, 28, and 32
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16
Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate a swollen joint count (SJC) ranging from 0 to 66 swollen joints and a tender joint count (TJC) ranging from 0 to 68 tender joints. Response was defined as a reduction from Baseline of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, Health Assessment Questionnaire Disability Index (HAQ-DI), or C-reactive protein (CRP); plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
Time frame: Baseline and Weeks 4, 8, 12, and 16
Percentage of Participants Achieving a Response According to ACR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab
Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate an SJC ranging from 0 to 66 swollen joints and a TJC ranging from 0 to 68 tender joints. Response was defined as a reduction from the reference visit (Week 16) of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, HAQ-DI, or CRP; plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
Time frame: Weeks 16 and 32
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate an SJC ranging from 0 to 66 swollen joints and a TJC ranging from 0 to 68 tender joints. Response was defined as a reduction from Baseline of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, HAQ-DI, or CRP; plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
Time frame: Baseline and Weeks 20, 24, 28, and 32
Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16
The CDAI was calculated as \[SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
Time frame: Baseline and Weeks 4, 8, 12, and 16
Change From Week 16 to 32 in CDAI and SDAI Scores Among Nonresponding Participants Treated With Rituximab
The CDAI was calculated as \[SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
Time frame: Weeks 16 and 32
Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
The CDAI was calculated as \[SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
Time frame: Baseline and Weeks 20, 24, 28, and 32
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, and 16
Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change from Baseline was calculated as \[mean hemoglobin at the assessment visit minus mean hemoglobin at Baseline\] and expressed in grams per liter (g/L).
Time frame: Baseline and Weeks 4, 8, 12, and 16
Change From Baseline in CRP at Weeks 4, 8, 12, and 16
Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change from Baseline was calculated as \[mean CRP at the assessment visit minus mean CRP at Baseline\] and expressed in milligrams per deciliter (mg/dL).
Time frame: Baseline and Weeks 4, 8, 12, and 16
Change From Baseline in ESR at Weeks 4, 8, 12, and 16
Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change from Baseline was calculated as \[mean ESR at the assessment visit minus mean ESR at Baseline\] and expressed in millimeters per hour (mm/h).
Time frame: Baseline and Weeks 4, 8, 12, and 16
Change in Hemoglobin From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change was calculated as \[mean hemoglobin at Week 32 minus mean hemoglobin at Week 16\] and expressed in g/L.
Time frame: Weeks 16 and 32
Change in CRP From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change was calculated as \[mean CRP at Week 32 minus mean CRP at Week 16\] and expressed in mg/dL.
Time frame: Weeks 16 and 32
Change in ESR From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab
Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change was calculated as \[mean ESR at Week 32 minus mean ESR at Week 16\] and expressed in mm/h.
Time frame: Weeks 16 and 32
Change From Baseline in Hemoglobin at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change from Baseline was calculated as \[mean hemoglobin at the assessment visit minus mean hemoglobin at Baseline\] and expressed in g/L.
Time frame: Baseline and Weeks 20, 24, 28, and 32
Change From Baseline in CRP at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change from Baseline was calculated as \[mean CRP at the assessment visit minus mean CRP at Baseline\] and expressed in mg/dL.
Time frame: Baseline and Weeks 20, 24, 28, and 32
Change From Baseline in ESR at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change from Baseline was calculated as \[mean ESR at the assessment visit minus mean ESR at Baseline\] and expressed in mm/h.
Time frame: Baseline and Weeks 20, 24, 28, and 32
Percentage of Participants Withdrawing From the Study for Insufficient Therapeutic Response
Study discontinuation was documented by reason for each participant prematurely withdrawing from the study. The percentage of participants was calculated as the number withdrawing for insufficient therapeutic response divided by the total number of participants who began treatment.
Time frame: Baseline to Week 16
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation \[CD\] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
Time frame: Baseline
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation \[CD\] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
Time frame: Baseline
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation \[CD\] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
Time frame: Baseline
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline to Week 16 in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) \>0.2, with greater values indicating a stronger correlation.
Time frame: Baseline and Week 16
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) \>0.2, with greater values indicating a stronger correlation.
Time frame: Baseline and Weeks 16, 24, and 32
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab
Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) \>0.2, with greater values indicating a stronger correlation.
Time frame: Baseline and Weeks 16, 32, 40, 48, and 66
Mean Number of Work Days Missed Per Week
Work days missed were documented by reason (either rheumatoid arthritis \[RA\] or other reasons) for each participant over the preceding 7-day period. The mean number of work days missed was calculated by averaging the number of days missed per week among all participants.
Time frame: Baseline and Week 16
Quality of Life as Assessed Using Short Form 36 (SF-36)
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants.
Time frame: Baseline and Week 16
Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as \[mean score at Week 16 minus mean score at Baseline\].
Time frame: Baseline and Week 16
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as \[mean score at Week 32 minus mean score at Week 16\].
Time frame: Weeks 16 and 32
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab
The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as \[mean score at Week 32 minus mean score at Week 16\].
Time frame: Weeks 16 and 32
Quality of Life as Assessed Using HAQ-DI
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants.
Time frame: Baseline and Week 16
Change From Baseline in Quality of Life as Assessed Using HAQ-DI at Week 16
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as \[mean score at Week 16 minus mean score at Baseline\].
Time frame: Baseline and Week 16
Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Participants Treated With 8 Courses of Tocilizumab
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as \[mean score at Week 32 minus the mean score at Week 16\].
Time frame: Weeks 16 and 32
Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Nonresponding Participants Treated With Rituximab
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as \[mean score at Week 32 minus the mean score at Week 16\].
Time frame: Weeks 16 and 32
Percentage of Participants Achieving a Response According to HAQ-DI Criteria
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. Response was defined as a change in index score \>0.22 from Baseline to Week 16.
Time frame: Baseline and Week 16
Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT)
The FACIT-F evaluates quality of life using 5 categories: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and fatigue (FS). Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-General (FACIT-G; range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-Fatigue (FACIT-F) trial outcome index (TOI; range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants.
Time frame: Baseline and Week 16
Change From Baseline in Quality of Life as Assessed Using FACIT at Week 16
The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as \[mean score at Week 16 minus mean score at Baseline\].
Time frame: Baseline and Week 16
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Participants Treated With 8 Courses of Tocilizumab
The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as \[mean score at Week 32 minus mean score at Week 16\].
Time frame: Weeks 16 and 32
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Nonresponding Participants Treated With Rituximab
The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as \[mean score at Week 32 minus mean score at Week 16\].
Time frame: Weeks 16 and 32
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Berlin, Germany
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Berlin, Germany
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