Rheumatoid Arthritis
Conditions
Brief summary
This 3 arm study assessed the efficacy of rituximab (MabThera®/Rituxan®) in the prevention of progression of structural joint damage in participants with active rheumatoid arthritis who had an inadequate clinical response to methotrexate. Participants were randomized to receive rituximab 500 mg intravenously (iv), rituximab 1000 mg iv, or placebo iv on days 1 and 15 every 24 weeks in the main study; all participants received concomitant methotrexate at a stable dose of 12.5-25 mg/week throughout the study. Further courses of rituximab were provided to eligible participants. Structural joint damage was assessed by magnetic resonance imaging (MRI) at baseline and at intervals during the study.
Detailed description
There were 3 phases in the study: A 52 week long main study, a study extension phase, and a 48 week long safety follow-up phase. The first course of treatment with placebo or rituximab was initiated on Day 1 of the 52 week long main study. A second course of treatment was initiated after Week 24, if the participant met eligibility criteria. After Week 52, eligible participants received further treatment courses at intervals ≥ 6 months in the study extension phase. No treatments were administered in the safety follow-up phase. Participants had to meet the following eligibility criteria to receive rituximab in the study extension phase. * Minimum of 24 weeks had passed since the first infusion of the last course of study medication. * C-reactive protein-based Disease Activity Score 28 (DAS28-CRP) ≥ 2.6. * Absolute neutrophil count not below 1.5 x 103/μL. * Patient had not developed contraindications for receiving rituximab, such as: 1. Any new or uncontrolled concomitant disease such as, but not limited to, cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders. 2. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection. 3. Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization, or treatment with iv anti-infectives within 4 weeks prior to infusion or completion of oral anti-infectives within 2 weeks prior to infusion. * Patient was not pregnant or breast feeding. * Patients who entered the study and were found to be hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (HBcAb) positive, were to be negative for hepatitis B viral DNA (\< 29 IU/mL) and were to have aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) results within the last 12 weeks.
Interventions
BIOLOGICALRituximab
Rituximab was supplied as a sterile liquid for iv administration.
DRUGPlacebo
Placebo was supplied as a sterile liquid in single-use vials for iv administration.
DRUGMethylprednisolone
DRUGMethotrexate
DRUGFolic acid or folate
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients, 18-80 years of age. * Active rheumatoid arthritis for ≥ 3 months and ≤ 10 years. * Evidence of erosive disease and/or clinical synovitis in a signal joint. * Inadequate response to 12.5-25 mg/week methotrexate for ≥ 12 weeks.
Exclusion criteria
* Rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis. - Any surgical procedure within 12 weeks prior to baseline. * Previous treatment with a biologic agent or with a B cell modulating or cell depleting therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Week 24 | Baseline to Week 24 | The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more erosion. A negative change score indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52 | Baseline to Week 52 | The synovitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images of 3 wrist regions and 5 metacarpophalangeal joints in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 3 with each integer unit increment representing a 33% enhancement of the maximum volume of enhancing tissue in the synovial compartment using the following scale: 0.0=normal, no synovitis; 0.5=1-17% estimated volume of enhancement; 1.0=18-33%; 1.5=34-50%; 2.0=51-67%; 2.5=68-83%; 3.0=84-100% estimated volume of enhancement. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more synovitis. A negative change score indicates improvement. |
| Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52 | Baseline to Week 52 | The osteitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Each location was scored in 0.5 increments from 0 to 3 with each integer unit increment representing a 33% increase in the volume of the peripheral 1 cm of original (eroded + residual) articular bone using the following scale: 0.0=normal, no osteitis; 0.5=1-17% involvement of original articular bone; 1.0=18-33%; 1.5=34-50%; 2.0=51-67%; 2.5=68-83%; 3.0=84-100% involvement of original articular bone. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more synovitis. A negative change score indicates improvement. |
| Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52 | Baseline to Week 52 | No newly eroded joints was defined as no new erosions in joints which were scored 0 at baseline. The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion. |
| Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Baseline to Week 52 | There were 2 definitions of no progression/no worsening in bone erosion. A participant met the criterion for definition 1 when there was a change in the magnetic resonance imaging erosion score ≤ 0. A participant met the criteria for definition 2 when there was either (1) no change from Baseline in the MRI erosion score, (2) an increase in erosion score and the size of the increase in score was smaller than the smallest detectable change, or (3) a drop in the erosion score. The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. |
| Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Baseline to Week 52 | There were 2 definitions of improvement in synovitis. A participant met the criterion for definition 1 when there was a drop in the magnetic resonance imaging synovitis score from Baseline \> 0.5. A participant met the criterion for definition 2 when there was a drop in the magnetic resonance imaging synovitis score from Baseline \> than the smallest detectable change. The synovitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI (RAMRIS) scoring system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. |
| Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Baseline to Week 52 | There were 2 definitions of improvement in osteitis. A participant met the criterion for definition 1 when there was a drop in the magnetic resonance imaging osteitis score from Baseline \> 0.5. A participant met the criterion for definition 2 when there was a drop in the magnetic resonance imaging osteitis score from Baseline \> than the smallest detectable change. The osteitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI (RAMRIS) scoring system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. |
| Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52 | Baseline to Week 52 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, C-reactive protein level (CRP), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. |
| Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52 | Baseline to Week 52 | The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more erosion. A negative change score indicates improvement. |
| Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52 | Baseline to Week 52 | The percentage of participants who had low rheumatic arthritis disease activity at Weeks 24 and 52, as measured by a DAS28 score ≤ 3.2, is reported. DAS28 is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]), and CRP = C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. |
| Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52 | Baseline to Week 52 | The percentage of participants in remission of their rheumatic arthritis at Weeks 24 and 52, as measured by a DAS28 score \< 2.6, is reported. DAS28 is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]), and CRP = C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. |
| Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Baseline to Week 52 | Improvement must be seen in tender and swollen joint counts (28 assessed joints; Joints were evaluated and classified as swollen or not swollen and tender or not tender based on pressure and joint manipulation upon physical examination) and in at least 3 |
| Percentage of Participants Achieving a Major Clinical Response at Week 52 | Baseline to Week 52 | A major clinical response was defined as an improvement of at least 70% in the American College of Rheumatology score from Baseline at Week 52. Improvement must be seen in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate participant and physician assessments of participant disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line no disease activity \[symptom-free and no arthritis symptoms\] and the extreme right end maximum disease activity); participant assessment of pain in previous the 24 hours on a VAS (extreme left end of the line no pain and the extreme right end unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein level. |
| Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Baseline to Week 52 | Correlation coefficients of magnetic resonance imaging erosion, synovitis, and osteitis scores and clinical outcome measures of swollen joint count (SJC), tender joint count (TJC), C-reactive protein level (CRP), erythrocyte sedimentation rate (ESR), a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (GH), Disease Activity Score 28-C-reactive protein (DAS28-CRP), and Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) are reported. Not all of these variables were specified as primary or secondary Outcome Measures in the study protocol and were not individually analyzed. |
| Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Baseline to Week 52 | The HAQ-DI assesses how well the patient is able to perform 8 activities: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The patient answers 20 questions with 1 of 4 responses with the past week as the time frame: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The highest score for any question in a category determines the category score. The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement. |
| Adverse Events (AEs), Laboratory Parameters, C-reactive Protein, ESR. | Throughout study | — |
| Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Baseline to Week 52 | Change of the DAS28 score from Baseline was used to determine the EULAR responses. For a post-Baseline score ≤ 3.2, a change from Baseline of \< -1.2 was a good response, \< -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-Baseline score \> 3.2 to ≤ 5.1, a change from Baseline of \< -0.6 was a moderate response and ≥ -0.6 was no response. For a post-Baseline score \> 5.1, a change from Baseline \< -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-Baseline scores \> 3.2. DAS28=(0.56×√(TJC28))+(0.28×√(SJC28))+(0.7×log(CRP))+(0.014×GH), where TJC28=tender joint count (JC) and SJC28=swollen JC (28 joints), GH=a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end=no disease activity, right end=maximum disease activity), and CRP=C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. |
Countries
Argentina, Brazil, Canada, Czechia, Denmark, Estonia, France, Germany, Greece, Latvia, Lithuania, Netherlands, Norway, Romania, Russia, Serbia, Spain, Switzerland, Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab 500 mg Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. | 62 |
| Rituximab 1000 mg Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. | 60 |
| Placebo Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. | 63 |
| Total | 185 |
Baseline characteristics
| Characteristic | Rituximab 500 mg | Rituximab 1000 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 48.7 years STANDARD_DEVIATION 11.1 | 50.7 years STANDARD_DEVIATION 11.65 | 50.3 years STANDARD_DEVIATION 11.94 | 49.9 years STANDARD_DEVIATION 11.54 |
| Sex: Female, Male Female | 45 Participants | 50 Participants | 48 Participants | 143 Participants |
| Sex: Female, Male Male | 17 Participants | 10 Participants | 15 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 62 | 24 / 60 | 20 / 63 | 0 / 50 | 0 / 47 | 0 / 41 | 0 / 57 | 0 / 54 | 0 / 54 |
| serious Total, serious adverse events | 3 / 62 | 4 / 60 | 5 / 63 | 3 / 50 | 5 / 47 | 2 / 41 | 0 / 57 | 1 / 54 | 0 / 54 |
Outcome results
Primary
Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Week 24
The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more erosion. A negative change score indicates improvement.
Time frame: Baseline to Week 24
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab 500 mg | Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Week 24 | 0.13 Units on a scale | Standard Deviation 2.258 |
| Rituximab 1000 mg | Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Week 24 | 0.39 Units on a scale | Standard Deviation 1.807 |
| Placebo | Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Week 24 | 1.33 Units on a scale | Standard Deviation 2.235 |
Secondary
Adverse Events (AEs), Laboratory Parameters, C-reactive Protein, ESR.
Time frame: Throughout study
Secondary
Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52
The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, C-reactive protein level (CRP), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 500 mg | Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52 | Week 24 (n = 63, 62, 59) | -1.714 Units on a scale | Standard Deviation 1.2204 |
| Rituximab 500 mg | Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) | -2.055 Units on a scale | Standard Deviation 1.1844 |
| Rituximab 1000 mg | Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52 | Week 24 (n = 63, 62, 59) | -1.683 Units on a scale | Standard Deviation 1.0158 |
| Rituximab 1000 mg | Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) | -1.801 Units on a scale | Standard Deviation 1.0443 |
| Placebo | Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52 | Week 24 (n = 63, 62, 59) | -0.752 Units on a scale | Standard Deviation 1.1834 |
| Placebo | Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) | -0.747 Units on a scale | Standard Deviation 1.2557 |
Secondary
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52
The HAQ-DI assesses how well the patient is able to perform 8 activities: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The patient answers 20 questions with 1 of 4 responses with the past week as the time frame: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The highest score for any question in a category determines the category score. The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 500 mg | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 24 (n = 63, 62, 59) | -0.425 Units on a scale | Standard Deviation 0.5606 |
| Rituximab 500 mg | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) | -0.520 Units on a scale | Standard Deviation 0.5873 |
| Rituximab 1000 mg | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 24 (n = 63, 62, 59) | -0.439 Units on a scale | Standard Deviation 0.477 |
| Rituximab 1000 mg | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) | -0.417 Units on a scale | Standard Deviation 0.445 |
| Placebo | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 24 (n = 63, 62, 59) | -0.194 Units on a scale | Standard Deviation 0.5849 |
| Placebo | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) | -0.177 Units on a scale | Standard Deviation 0.5943 |
Secondary
Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52
The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more erosion. A negative change score indicates improvement.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 500 mg | Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52 | Week 12 (n = 58, 58, 56) | 0.42 Units on a scale | Standard Deviation 1.693 |
| Rituximab 500 mg | Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52 | Week 52 (n = 56, 57, 58) | 0.11 Units on a scale | Standard Deviation 2.623 |
| Rituximab 1000 mg | Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52 | Week 12 (n = 58, 58, 56) | 0.13 Units on a scale | Standard Deviation 1.764 |
| Rituximab 1000 mg | Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52 | Week 52 (n = 56, 57, 58) | -0.30 Units on a scale | Standard Deviation 2.372 |
| Placebo | Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52 | Week 12 (n = 58, 58, 56) | 0.33 Units on a scale | Standard Deviation 4.122 |
| Placebo | Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52 | Week 52 (n = 56, 57, 58) | 3.02 Units on a scale | Standard Deviation 4.456 |
Secondary
Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52
The osteitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Each location was scored in 0.5 increments from 0 to 3 with each integer unit increment representing a 33% increase in the volume of the peripheral 1 cm of original (eroded + residual) articular bone using the following scale: 0.0=normal, no osteitis; 0.5=1-17% involvement of original articular bone; 1.0=18-33%; 1.5=34-50%; 2.0=51-67%; 2.5=68-83%; 3.0=84-100% involvement of original articular bone. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more synovitis. A negative change score indicates improvement.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 500 mg | Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 24 (n = 61, 59, 59) | -2.91 Units on a scale | Standard Deviation 5.687 |
| Rituximab 500 mg | Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 12 (n = 58, 58, 56) | -2.11 Units on a scale | Standard Deviation 5.049 |
| Rituximab 500 mg | Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 52 (n = 61, 59, 59) | -4.75 Units on a scale | Standard Deviation 7.413 |
| Rituximab 1000 mg | Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 24 (n = 61, 59, 59) | -2.86 Units on a scale | Standard Deviation 5.976 |
| Rituximab 1000 mg | Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 12 (n = 58, 58, 56) | -1.88 Units on a scale | Standard Deviation 5.366 |
| Rituximab 1000 mg | Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 52 (n = 61, 59, 59) | -3.83 Units on a scale | Standard Deviation 6.255 |
| Placebo | Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 12 (n = 58, 58, 56) | -0.14 Units on a scale | Standard Deviation 3.94 |
| Placebo | Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 52 (n = 61, 59, 59) | -0.22 Units on a scale | Standard Deviation 6.39 |
| Placebo | Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 24 (n = 61, 59, 59) | 0.07 Units on a scale | Standard Deviation 5.574 |
Secondary
Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52
The synovitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images of 3 wrist regions and 5 metacarpophalangeal joints in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 3 with each integer unit increment representing a 33% enhancement of the maximum volume of enhancing tissue in the synovial compartment using the following scale: 0.0=normal, no synovitis; 0.5=1-17% estimated volume of enhancement; 1.0=18-33%; 1.5=34-50%; 2.0=51-67%; 2.5=68-83%; 3.0=84-100% estimated volume of enhancement. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more synovitis. A negative change score indicates improvement.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 500 mg | Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 24 (n = 61, 59, 59) | -1.14 Units on a scale | Standard Deviation 1.923 |
| Rituximab 500 mg | Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 12 (n = 58, 58, 56) | -0.50 Units on a scale | Standard Deviation 1.701 |
| Rituximab 500 mg | Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 52 (n = 61, 59, 59) | -2.03 Units on a scale | Standard Deviation 2.562 |
| Rituximab 1000 mg | Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 24 (n = 61, 59, 59) | -1.81 Units on a scale | Standard Deviation 2.289 |
| Rituximab 1000 mg | Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 12 (n = 58, 58, 56) | -1.15 Units on a scale | Standard Deviation 1.866 |
| Rituximab 1000 mg | Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 52 (n = 61, 59, 59) | -2.73 Units on a scale | Standard Deviation 3.12 |
| Placebo | Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 12 (n = 58, 58, 56) | -0.22 Units on a scale | Standard Deviation 2.05 |
| Placebo | Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 52 (n = 61, 59, 59) | -0.01 Units on a scale | Standard Deviation 2.7 |
| Placebo | Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52 | Week 24 (n = 61, 59, 59) | 0.20 Units on a scale | Standard Deviation 2.257 |
Secondary
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Correlation coefficients of magnetic resonance imaging erosion, synovitis, and osteitis scores and clinical outcome measures of swollen joint count (SJC), tender joint count (TJC), C-reactive protein level (CRP), erythrocyte sedimentation rate (ESR), a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (GH), Disease Activity Score 28-C-reactive protein (DAS28-CRP), and Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) are reported. Not all of these variables were specified as primary or secondary Outcome Measures in the study protocol and were not individually analyzed.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and TJC - Week 24 | 0.336 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and SJC - Week 24 | 0.341 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and SJC - Week 52 | 0.287 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and SJC - Week 24 | 0.329 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and SJC - Week 52 | 0.168 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and SJC - Week 24 | 0.407 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and SJC - Week 52 | 0.265 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and TJC - Week 24 | 0.364 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and TJC - Week 52 | 0.275 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and TJC - Week 52 | 0.142 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and TJC - Week 24 | 0.355 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and TJC - Week 52 | 0.245 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and CRP - Week 24 | 0.185 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and CRP - Week 52 | 0.055 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and CRP - Week 24 | 0.030 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and CRP - Week 52 | -0.077 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and CRP - Week 24 | -0.031 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and CRP - Week 52 | 0.005 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and ESR - Week 24 | 0.321 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and ESR - Week 52 | 0.127 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and ESR - Week 24 | 0.182 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and ESR - Week 52 | 0.185 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and ESR - Week 24 | 0.044 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and ESR - Week 52 | -0.041 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and GH - Week 24 | 0.206 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and GH - Week 52 | 0.063 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and GH - Week 24 | 0.186 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and GH - Week 52 | -0.026 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and GH - Week 24 | 0.274 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and GH - Week 52 | 0.106 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-CRP - Week 24 | 0.420 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-CRP - Week 52 | 0.238 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-CRP - Week 24 | 0.393 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-CRP - Week 52 | 0.149 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-CRP - Week 24 | 0.380 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-CRP - Week 52 | 0.139 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-ESR - Week 24 | 0.429 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-ESR - Week 52 | 0.244 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-ESR - Week 24 | 0.398 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-ESR - Week 52 | 0.198 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-ESR - Week 24 | 0.353 Correlation coefficient |
| Rituximab 500 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-ESR - Week 52 | 0.108 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-ESR - Week 52 | 0.180 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and GH - Week 24 | 0.122 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and SJC - Week 24 | 0.425 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-CRP - Week 52 | 0.150 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and ESR - Week 52 | 0.248 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and SJC - Week 52 | 0.234 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-ESR - Week 52 | 0.147 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-CRP - Week 52 | 0.143 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and SJC - Week 24 | 0.389 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and ESR - Week 24 | 0.043 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and GH - Week 52 | 0.052 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and SJC - Week 52 | 0.188 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and ESR - Week 24 | 0.136 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and CRP - Week 24 | -0.057 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and SJC - Week 24 | 0.354 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and ESR - Week 52 | 0.116 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-CRP - Week 24 | 0.209 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and SJC - Week 52 | 0.192 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-ESR - Week 52 | 0.172 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-CRP - Week 24 | 0.198 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and TJC - Week 24 | 0.115 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and GH - Week 24 | 0.043 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and ESR - Week 52 | 0.188 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and TJC - Week 52 | 0.067 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-ESR - Week 24 | 0.255 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and TJC - Week 24 | 0.174 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and GH - Week 52 | -0.009 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-ESR - Week 24 | 0.332 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and TJC - Week 52 | 0.036 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and CRP - Week 52 | 0.085 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-CRP - Week 52 | 0.127 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and TJC - Week 24 | 0.118 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and CRP - Week 24 | 0.090 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and GH - Week 24 | 0.221 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and TJC - Week 52 | 0.048 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and ESR - Week 24 | 0.214 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-ESR - Week 24 | 0.231 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and CRP - Week 24 | -0.024 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and GH - Week 52 | -0.037 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-CRP - Week 24 | 0.349 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and CRP - Week 52 | 0.098 Correlation coefficient |
| Rituximab 1000 mg | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and CRP - Week 52 | -0.010 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and CRP - Week 52 | 0.352 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and CRP - Week 24 | 0.192 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-ESR - Week 52 | 0.356 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and CRP - Week 52 | 0.311 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and CRP - Week 24 | 0.040 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-CRP - Week 52 | 0.500 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and CRP - Week 52 | 0.119 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and ESR - Week 24 | 0.197 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and ESR - Week 52 | 0.314 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-CRP - Week 24 | 0.351 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and ESR - Week 24 | 0.358 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-ESR - Week 52 | 0.514 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and ESR - Week 52 | 0.360 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and ESR - Week 24 | 0.148 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-CRP - Week 52 | 0.356 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and ESR - Week 52 | 0.205 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and GH - Week 24 | 0.326 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and GH - Week 52 | 0.316 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-ESR - Week 24 | 0.439 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and GH - Week 24 | 0.206 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and GH - Week 52 | 0.286 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and SJC - Week 24 | 0.446 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and GH - Week 24 | 0.205 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and SJC - Week 52 | 0.355 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-ESR - Week 52 | 0.473 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and SJC - Week 24 | 0.566 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and SJC - Week 52 | 0.574 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and GH - Week 52 | 0.136 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and SJC - Week 24 | 0.370 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and DAS28-ESR - Week 24 | 0.353 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and SJC - Week 52 | 0.398 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and TJC - Week 24 | 0.298 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-CRP - Week 24 | 0.457 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and TJC - Week 52 | 0.425 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and TJC - Week 24 | 0.282 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and TJC - Week 52 | 0.421 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and TJC - Week 24 | 0.288 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and DAS28-CRP - Week 52 | 0.498 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Osteitis score and TJC - Week 52 | 0.371 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-ESR - Week 24 | 0.438 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Erosion score and CRP - Week 24 | 0.006 Correlation coefficient |
| Placebo | Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures | Synovitis score and DAS28-CRP - Week 24 | 0.437 Correlation coefficient |
Secondary
Percentage of Participants Achieving a Major Clinical Response at Week 52
A major clinical response was defined as an improvement of at least 70% in the American College of Rheumatology score from Baseline at Week 52. Improvement must be seen in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate participant and physician assessments of participant disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line no disease activity \[symptom-free and no arthritis symptoms\] and the extreme right end maximum disease activity); participant assessment of pain in previous the 24 hours on a VAS (extreme left end of the line no pain and the extreme right end unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein level.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab 500 mg | Percentage of Participants Achieving a Major Clinical Response at Week 52 | 6.5 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants Achieving a Major Clinical Response at Week 52 | 6.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving a Major Clinical Response at Week 52 | 1.6 Percentage of participants |
Secondary
Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52
The percentage of participants in remission of their rheumatic arthritis at Weeks 24 and 52, as measured by a DAS28 score \< 2.6, is reported. DAS28 is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]), and CRP = C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 500 mg | Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52 | Week 24 | 21.0 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52 | Week 52 | 25.8 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52 | Week 24 | 28.3 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52 | Week 52 | 25.0 Percentage of participants |
| Placebo | Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52 | Week 24 | 12.7 Percentage of participants |
| Placebo | Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52 | Week 52 | 7.9 Percentage of participants |
Secondary
Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52
Improvement must be seen in tender and swollen joint counts (28 assessed joints; Joints were evaluated and classified as swollen or not swollen and tender or not tender based on pressure and joint manipulation upon physical examination) and in at least 3
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 500 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 24 - ACR20 response | 51.6 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 24 - ACR50 response | 24.2 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 24 - ACR70 response | 11.3 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 52 - ACR20 response | 67.7 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 52 - ACR50 response | 37.1 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 52 - ACR70 response | 17.7 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 52 - ACR70 response | 16.7 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 24 - ACR20 response | 51.7 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 52 - ACR20 response | 68.3 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 52 - ACR50 response | 35.0 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 24 - ACR50 response | 26.7 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 24 - ACR70 response | 8.3 Percentage of participants |
| Placebo | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 24 - ACR50 response | 11.1 Percentage of participants |
| Placebo | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 24 - ACR70 response | 1.6 Percentage of participants |
| Placebo | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 52 - ACR70 response | 6.3 Percentage of participants |
| Placebo | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 52 - ACR20 response | 28.6 Percentage of participants |
| Placebo | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 24 - ACR20 response | 28.6 Percentage of participants |
| Placebo | Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52 | Week 52 - ACR50 response | 14.3 Percentage of participants |
Secondary
Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52
Change of the DAS28 score from Baseline was used to determine the EULAR responses. For a post-Baseline score ≤ 3.2, a change from Baseline of \< -1.2 was a good response, \< -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-Baseline score \> 3.2 to ≤ 5.1, a change from Baseline of \< -0.6 was a moderate response and ≥ -0.6 was no response. For a post-Baseline score \> 5.1, a change from Baseline \< -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-Baseline scores \> 3.2. DAS28=(0.56×√(TJC28))+(0.28×√(SJC28))+(0.7×log(CRP))+(0.014×GH), where TJC28=tender joint count (JC) and SJC28=swollen JC (28 joints), GH=a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end=no disease activity, right end=maximum disease activity), and CRP=C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 500 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 24 - No response | 33.9 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 24 - Moderate response | 37.1 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 24 - Good response | 29.0 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) - No response | 21.0 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) - Moderate response | 45.2 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) - Good response | 33.9 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) - Good response | 37.3 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 24 - No response | 22.0 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) - No response | 13.6 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) - Moderate response | 49.2 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 24 - Moderate response | 42.4 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 24 - Good response | 35.6 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 24 - Moderate response | 22.2 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 24 - Good response | 19.0 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) - Good response | 7.9 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) - No response | 60.3 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 24 - No response | 58.7 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52 | Week 52 (n = 63, 62, 59) - Moderate response | 31.7 Percentage of participants |
Secondary
Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52
There were 2 definitions of improvement in osteitis. A participant met the criterion for definition 1 when there was a drop in the magnetic resonance imaging osteitis score from Baseline \> 0.5. A participant met the criterion for definition 2 when there was a drop in the magnetic resonance imaging osteitis score from Baseline \> than the smallest detectable change. The osteitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI (RAMRIS) scoring system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 500 mg | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 24 (Definition 1) | 50.0 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 24 (Definition 2) | 50.0 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 52 (Definition 1) | 58.1 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 52 (Definition 2) | 58.1 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 52 (Definition 2) | 51.7 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 24 (Definition 1) | 51.7 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 52 (Definition 1) | 51.7 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 24 (Definition 2) | 51.7 Percentage of participants |
| Placebo | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 52 (Definition 2) | 27.0 Percentage of participants |
| Placebo | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 24 (Definition 2) | 22.2 Percentage of participants |
| Placebo | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 52 (Definition 1) | 27.0 Percentage of participants |
| Placebo | Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52 | Week 24 (Definition 1) | 22.2 Percentage of participants |
Secondary
Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52
There were 2 definitions of improvement in synovitis. A participant met the criterion for definition 1 when there was a drop in the magnetic resonance imaging synovitis score from Baseline \> 0.5. A participant met the criterion for definition 2 when there was a drop in the magnetic resonance imaging synovitis score from Baseline \> than the smallest detectable change. The synovitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI (RAMRIS) scoring system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 500 mg | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 24 (Definition 1) | 41.9 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 24 (Definition 2) | 41.9 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 52 (Definition 1) | 54.8 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 52 (Definition 2) | 54.8 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 52 (Definition 2) | 60.0 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 24 (Definition 1) | 56.7 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 52 (Definition 1) | 60.0 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 24 (Definition 2) | 56.7 Percentage of participants |
| Placebo | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 52 (Definition 2) | 25.4 Percentage of participants |
| Placebo | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 24 (Definition 2) | 22.2 Percentage of participants |
| Placebo | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 52 (Definition 1) | 25.4 Percentage of participants |
| Placebo | Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52 | Week 24 (Definition 1) | 22.2 Percentage of participants |
Secondary
Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52
The percentage of participants who had low rheumatic arthritis disease activity at Weeks 24 and 52, as measured by a DAS28 score ≤ 3.2, is reported. DAS28 is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]), and CRP = C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 500 mg | Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52 | Week 24 | 33.9 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52 | Week 52 | 37.1 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52 | Week 24 | 36.7 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52 | Week 52 | 38.3 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52 | Week 24 | 19.0 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52 | Week 52 | 9.5 Percentage of participants |
Secondary
Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52
No newly eroded joints was defined as no new erosions in joints which were scored 0 at baseline. The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 500 mg | Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52 | Week 24 | 77.4 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52 | Week 52 | 77.4 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52 | Week 52 | 40 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52 | Week 24 | 73.3 Percentage of participants |
| Placebo | Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52 | Week 24 | 55.5 Percentage of participants |
| Placebo | Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52 | Week 52 | 60.3 Percentage of participants |
Secondary
Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52
There were 2 definitions of no progression/no worsening in bone erosion. A participant met the criterion for definition 1 when there was a change in the magnetic resonance imaging erosion score ≤ 0. A participant met the criteria for definition 2 when there was either (1) no change from Baseline in the MRI erosion score, (2) an increase in erosion score and the size of the increase in score was smaller than the smallest detectable change, or (3) a drop in the erosion score. The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 500 mg | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 24 (Definition 1) | 50.0 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 24 (Definition 2) | 88.7 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 52 (Definition 1) | 48.4 Percentage of participants |
| Rituximab 500 mg | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 52 (Definition 2) | 85.5 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 52 (Definition 2) | 93.3 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 24 (Definition 1) | 51.7 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 52 (Definition 1) | 55.0 Percentage of participants |
| Rituximab 1000 mg | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 24 (Definition 2) | 96.7 Percentage of participants |
| Placebo | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 52 (Definition 2) | 55.6 Percentage of participants |
| Placebo | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 24 (Definition 2) | 81.0 Percentage of participants |
| Placebo | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 52 (Definition 1) | 27.0 Percentage of participants |
| Placebo | Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52 | Week 24 (Definition 1) | 33.3 Percentage of participants |