Rheumatoid Arthritis
Conditions
Brief summary
This study will evaluate the safety and effectiveness of MabThera (rituximab) in patients with active rheumatoid arthritis who are receiving methotrexate, and who have a previous or current inadequate response to one prior anti-TNF therapy. All patients will receive MabThera 1000 mg as an intravenous infusion on days 1 and 15. After the initial study phase of 24 weeks, eligible patients may receive one re-treatment with MabThera. The anticipated time on study treatment is 48 weeks.
Interventions
DRUGrituximab
1000 mg intravenously on Days 1 and 15
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients, 18-80 years of age * Moderate to severe active rheumatoid arthritis * Inadequate response to a single previous or current treatment with an anti-TNF agent * Methotrexate for at least 12 weeks, at a stable dose over the past 4 weeks
Exclusion criteria
* Previous treatment with MabThera * Use of an anti-TNF agent within past 8 weeks (4 in the case of etanercept) * Concurrent treatment with any Disease Modifying Anti-Rheumatic Drug (DMARD) other than methotrexate * Active infection, or history of serious or chronic infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary | Days 1, 2, 15, and 16 and Week 48 of Initial treatment period | Percentage of participants who reported an AE or serious AE (SAE), a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | ACR20/50/70, defined as ≥20 percent (%), 50%, or 70% improvement, respectively, compared to baseline in tender joint count (TJC) and swollen joint count (SJC), and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and an acute phase reactant (erythrocyte sedimentation rate \[ESR\] or C-Reactive Protein \[CRP\]). If CRP was missing or not done, then ESR was used. |
| Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | Complete clinical response was defined as having an ACR70 for at least 13 weeks. |
| Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period | Weeks 12 and 24 of Re-treatment period | ACR20/50/70, defined as ≥20%, 50%, or 70% improvement, respectively, compared to baseline in TJC and SJC, and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; HAQ-DI; and an acute phase reactant (ESR or CRP). If CRP was missing or not done, then ESR was used. |
| Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | Complete clinical response was defined as having an ACR70 for at least 13 weeks. |
| Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | The EULAR response criteria were based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score less than or equal to \[≤\]3.2), moderate (DAS28 score greater than \[\>\]3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria. |
| Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | The EULAR response criteria were based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria. |
| Change From Baseline in DAS28 During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria. A change of 1.2 units in DAS28 in an individual participant was considered a significant change. |
| Change From Baseline in DAS28 During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | The DAS28 scoring used 4 core components: SJC, TJC, Patient Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria. A change of 1.2 units in DAS28 in an individual participant was considered a significant change. |
| Change From Baseline in SJC During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees. |
| Change From Baseline in SJC During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees. |
| Change From Baseline in TJC During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees. |
| Change From Baseline in TJC During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees. |
| Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | Physician Global Assessment of Disease Activity was measured using a 100-mm visual analog scale (VAS) where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The physician marked the line and the distance from the left edge was measured in mm. |
| Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | Physician Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The physician marked the line and the distance from the left edge was measured in mm. |
| Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary | Days 1, 2, 15, and 16 and Week 48 of Re-treatment period | Percentage of participants who reported an AE or SAE, a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died. |
| Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period and Week 4 after last maintenance | Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The participant was asked to marked the line and the distance from the left edge was measured in mm. |
| Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain. The participant was asked to mark the line and the distance from the left edge was measured in mm. |
| Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain. The participant was asked to mark the line and the distance from the left edge was measured in mm. |
| Change From Baseline HAQ-DI Score During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities. Participants report amount of difficulty in performing 2-3 specific subcategory items. Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do). The highest component score in each of the 8 categories determined the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3). The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability). HAQ-DI not computed if \> 2 categories were missing. |
| Change From Baseline HAQ-DI Score During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities. Participants report amount of difficulty in performing 2-3 specific subcategory items. Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do). The highest component score in each of the 8 categories determines the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3). The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability). HAQ-DI not computed if \>2 categories were missing. |
| Change From Baseline in ESR During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | ESR was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr. |
| Change From Baseline in ESR During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | ESR was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr. |
| Change From Baseline in CRP During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | CRP levels were measured in milligrams/liter (mg/L) and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L. |
| Change From Baseline CRP During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | CRP levels were measured in mg/L and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L. |
| Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria. |
| Percentage of Participants With Disease Remission According to DAS28 in the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale. The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue. Score changes of 4 points or more were considered clinically meaningful. The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring. |
| Change From Baseline in FACIT-F Total Score During the Re-Treatment Period | Weeks 12 and 24 of Re-treatment period | Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale. The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue. Score changes of 4 points or more were considered clinically meaningful. The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring. |
| Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period | Weeks 4, 12, 24, 36, and 48 of Initial treatment period | Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The participant was asked to marked the line and the distance from the left edge was measured in mm. |
Countries
Canada, Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab + MTX Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48. | 120 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Initial Treatment Period | Adverse Event | 1 |
| Initial Treatment Period | Lack of Efficacy | 5 |
| Initial Treatment Period | Protocol Violation | 1 |
| Initial Treatment Period | Withdrawal by Subject | 1 |
| Re-Treatment Period | Adverse Event | 2 |
| Re-Treatment Period | Lack of Efficacy | 3 |
| Re-Treatment Period | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Rituximab + MTX |
|---|---|
| Age, Continuous | 55.6 years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 87 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 102 / 120 | 53 / 77 |
| serious Total, serious adverse events | 12 / 120 | 7 / 77 |
Outcome results
Primary
Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary
Percentage of participants who reported an AE or serious AE (SAE), a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.
Time frame: Days 1, 2, 15, and 16 and Week 48 of Initial treatment period
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary | With an AE | 85.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary | With a drug-related AE | 41.7 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary | With an acute infusion reaction | 20.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary | With AE leading to study drug discontinuation | 4.2 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary | With an SAE | 10.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary | With infections | 47.5 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary | With a serious infections | 2.5 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary | Who died | 0 percentage of participants |
Secondary
Change From Baseline CRP During the Re-Treatment Period
CRP levels were measured in mg/L and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline CRP During the Re-Treatment Period | Baseline (n=119) | 25.6 mg/L | Standard Deviation 28.87 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline CRP During the Re-Treatment Period | Change at Week 12 (n=70) | -16.9 mg/L | Standard Deviation 27.15 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline CRP During the Re-Treatment Period | Change at Week 24 (n=67) | -15.3 mg/L | Standard Deviation 26.62 |
Secondary
Change From Baseline HAQ-DI Score During the Initial Treatment Period
HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities. Participants report amount of difficulty in performing 2-3 specific subcategory items. Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do). The highest component score in each of the 8 categories determined the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3). The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability). HAQ-DI not computed if \> 2 categories were missing.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline HAQ-DI Score During the Initial Treatment Period | Baseline (n=120) | 1.7 scores on a scale | Standard Deviation 0.57 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline HAQ-DI Score During the Initial Treatment Period | Change at Week 4 (n=117) | -0.2 scores on a scale | Standard Deviation 0.36 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline HAQ-DI Score During the Initial Treatment Period | Change at Week 12 (n=116) | -0.3 scores on a scale | Standard Deviation 0.46 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline HAQ-DI Score During the Initial Treatment Period | Change at Week 24 (n=108) | -0.4 scores on a scale | Standard Deviation 0.48 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline HAQ-DI Score During the Initial Treatment Period | Change at Week 36 (n=68) | -0.3 scores on a scale | Standard Deviation 0.53 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline HAQ-DI Score During the Initial Treatment Period | Change at Week 48 (n=34) | -0.4 scores on a scale | Standard Deviation 0.56 |
Comparison: Baseline vs Week 24p-value: <0.001Wilcoxon Signed Rank test
Secondary
Change From Baseline HAQ-DI Score During the Re-Treatment Period
HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities. Participants report amount of difficulty in performing 2-3 specific subcategory items. Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do). The highest component score in each of the 8 categories determines the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3). The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability). HAQ-DI not computed if \>2 categories were missing.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline HAQ-DI Score During the Re-Treatment Period | Baseline (n=120) | 1.7 scores on a scale | Standard Deviation 0.57 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline HAQ-DI Score During the Re-Treatment Period | Change at Week 12 (n=73) | -0.5 scores on a scale | Standard Deviation 0.6 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline HAQ-DI Score During the Re-Treatment Period | Change at Week 24 (n=72) | -0.5 scores on a scale | Standard Deviation 0.62 |
Secondary
Change From Baseline in CRP During the Initial Treatment Period
CRP levels were measured in milligrams/liter (mg/L) and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in CRP During the Initial Treatment Period | Baseline (n=119) | 25.6 mg/L | Standard Deviation 28.87 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in CRP During the Initial Treatment Period | Change at Week 4 (n=110) | -7.9 mg/L | Standard Deviation 17.44 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in CRP During the Initial Treatment Period | Change at Week 12 (n=113) | -11.9 mg/L | Standard Deviation 31.97 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in CRP During the Initial Treatment Period | Change at Week 24 (n=108) | -16.1 mg/L | Standard Deviation 24.82 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in CRP During the Initial Treatment Period | Change at Week 36 (n=67) | -9.1 mg/L | Standard Deviation 25.74 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in CRP During the Initial Treatment Period | Change at Week 48 (n=34) | -7.6 mg/L | Standard Deviation 27.06 |
Comparison: Baseline vs Week 24p-value: <0.001Wilcoxon Signed Rank test
Secondary
Change From Baseline in DAS28 During the Initial Treatment Period
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria. A change of 1.2 units in DAS28 in an individual participant was considered a significant change.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population; n (number) = number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in DAS28 During the Initial Treatment Period | Baseline (n=117) | 6.4 scores on a scale | Standard Deviation 1.1 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in DAS28 During the Initial Treatment Period | Change at Week 4 (n=112) | -1.1 scores on a scale | Standard Deviation 0.8 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in DAS28 During the Initial Treatment Period | Change at Week 12 (n=108) | -1.7 scores on a scale | Standard Deviation 1.2 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in DAS28 During the Initial Treatment Period | Change at Week 24 (n=105) | -2.0 scores on a scale | Standard Deviation 1.2 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in DAS28 During the Initial Treatment Period | Change at Week 36 (n=66) | -1.7 scores on a scale | Standard Deviation 1.7 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in DAS28 During the Initial Treatment Period | Change at Week 48 (n=33) | -2.1 scores on a scale | Standard Deviation 1.6 |
Comparison: Week 4p-value: <0.001t-test, 1 sided
Comparison: Week 12p-value: <0.001t-test, 1 sided
Comparison: Week 24p-value: <0.001t-test, 1 sided
Comparison: Week 36p-value: <0.001t-test, 1 sided
Comparison: Week 48p-value: <0.001t-test, 1 sided
Secondary
Change From Baseline in DAS28 During the Re-Treatment Period
The DAS28 scoring used 4 core components: SJC, TJC, Patient Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria. A change of 1.2 units in DAS28 in an individual participant was considered a significant change.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in DAS28 During the Re-Treatment Period | Baseline (n=117) | 6.4 scores on a scale | Standard Deviation 1.1 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in DAS28 During the Re-Treatment Period | Change at Week 12 (n=70) | -2.3 scores on a scale | Standard Deviation 1.3 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in DAS28 During the Re-Treatment Period | Change at Week 24 (n=65) | -2.2 scores on a scale | Standard Deviation 1.4 |
Secondary
Change From Baseline in ESR During the Initial Treatment Period
ESR was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in ESR During the Initial Treatment Period | Baseline (n=120) | 37.0 mm/hr | Standard Deviation 27.84 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in ESR During the Initial Treatment Period | Change at Week 4 (n=112) | -4.5 mm/hr | Standard Deviation 13.57 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in ESR During the Initial Treatment Period | Change at Week 12 (n=112) | -11.3 mm/hr | Standard Deviation 20.6 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in ESR During the Initial Treatment Period | Change at Week 24 (n=107) | -16.0 mm/hr | Standard Deviation 20.36 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in ESR During the Initial Treatment Period | Change at Week 36 (n=68) | -9.2 mm/hr | Standard Deviation 22.29 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in ESR During the Initial Treatment Period | Change at Week 48 (n=34) | -12.0 mm/hr | Standard Deviation 17.93 |
Comparison: Baseline vs Week 24p-value: <0.001Wilcoxon Signed Rank test
Secondary
Change From Baseline in ESR During the Re-Treatment Period
ESR was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in ESR During the Re-Treatment Period | Baseline (n=120) | 37.0 mm/hr | Standard Deviation 27.84 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in ESR During the Re-Treatment Period | Change at Week 12 (n=73) | -17.9 mm/hr | Standard Deviation 22.07 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in ESR During the Re-Treatment Period | Change at Week 24 (n=67) | -18.7 mm/hr | Standard Deviation 23.05 |
Secondary
Change From Baseline in FACIT-F Total Score During the Re-Treatment Period
Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale. The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue. Score changes of 4 points or more were considered clinically meaningful. The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in FACIT-F Total Score During the Re-Treatment Period | Baseline (n=120) | 28.9 scores on a scale | Standard Deviation 10.22 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in FACIT-F Total Score During the Re-Treatment Period | Change at Week 12 (n=73) | -8.3 scores on a scale | Standard Deviation 12.64 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in FACIT-F Total Score During the Re-Treatment Period | Change at Week 24 (n=72) | -8.9 scores on a scale | Standard Deviation 11.72 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period
Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale. The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue. Score changes of 4 points or more were considered clinically meaningful. The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period | Baseline (n=120) | 28.9 scores on a scale | Standard Deviation 10.22 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period | Change at Week 4 (n=116) | -5.4 scores on a scale | Standard Deviation 8.19 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period | Change at Week 12 (n=116) | -7.3 scores on a scale | Standard Deviation 10.38 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period | Change at Week 24 (n=108) | -9.1 scores on a scale | Standard Deviation 9.9 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period | Change at Week 36 (n=68) | -8.6 scores on a scale | Standard Deviation 11.71 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period | Change at Week 48 (n=34) | -10.9 scores on a scale | Standard Deviation 10.68 |
Comparison: Baseline vs Week 12p-value: <0.001t-test, 1 sided
Comparison: Baseline vs Week 24p-value: <0.001Wilcoxon Signed Rank test
Secondary
Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period
Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The participant was asked to marked the line and the distance from the left edge was measured in mm.
Time frame: Weeks 12 and 24 of Re-treatment period and Week 4 after last maintenance
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period | Baseline (n=120) | 67.5 mm | Standard Deviation 22.73 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period | Change at Week 12 (n=72) | -32.6 mm | Standard Deviation 29.2 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period | Change at Week 24 (n=72) | -30.7 mm | Standard Deviation 28.7 |
Secondary
Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period
Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The participant was asked to marked the line and the distance from the left edge was measured in mm.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period | Baseline (n=120) | 67.5 mm | Standard Deviation 22.73 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period | Change at Week 4 (n=117) | -19.7 mm | Standard Deviation 21.5 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period | Change at Week 12 (n=116) | -26.3 mm | Standard Deviation 26.84 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period | Change at Week 24 (n=109) | -29.2 mm | Standard Deviation 25.72 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period | Change at Week 36 (n=68) | -23.8 mm | Standard Deviation 30.42 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period | Change at Week 48 (n=34) | -28.5 mm | Standard Deviation 22.92 |
Comparison: Baseline vs Week 24p-value: <0.001Wilcoxon Signed Rank test
Secondary
Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period
Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain. The participant was asked to mark the line and the distance from the left edge was measured in mm.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period | Change at Week 4 (n=117) | -17.5 mm | Standard Deviation 21.8 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period | Change at Week 12 (n=113) | -24.0 mm | Standard Deviation 25.31 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period | Change at Week 24 (n=108) | -25.7 mm | Standard Deviation 25.4 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period | Baseline (n=120) | 60.2 mm | Standard Deviation 22.85 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period | Change at Week 36 (n=68) | -18.0 mm | Standard Deviation 29.18 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period | Change at Week 48 (n=33) | -22.6 mm | Standard Deviation 20.07 |
Comparison: Baseline vs Week 24p-value: <0.001t-test, 1 sided
Secondary
Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period
Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain. The participant was asked to mark the line and the distance from the left edge was measured in mm.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period | Baseline (n=120) | 60.2 mm | Standard Deviation 22.85 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period | Change at Week 12 (n=72) | -28.3 mm | Standard Deviation 28.02 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period | Change at Week 24 (n=72) | -26.6 mm | Standard Deviation 27.61 |
Secondary
Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period
Physician Global Assessment of Disease Activity was measured using a 100-mm visual analog scale (VAS) where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The physician marked the line and the distance from the left edge was measured in mm.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period | Baseline (n=120) | 68.6 mm | Standard Deviation 17.34 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period | Change at Week 4 (n=117) | -22.0 mm | Standard Deviation 21.67 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period | Change at Week 12 (n=116) | -31.4 mm | Standard Deviation 24.28 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period | Change at Week 24 (n=109) | -35.1 mm | Standard Deviation 24.45 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period | Change at Week 36 (n=68) | -28.6 mm | Standard Deviation 28.68 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period | Change at Week 48 (n=34) | -35.9 mm | Standard Deviation 25.18 |
Comparison: Baseline vs Week 24p-value: <0.001t-test, 1 sided
Secondary
Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period
Physician Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The physician marked the line and the distance from the left edge was measured in mm.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period | Baseline (n=120) | 68.6 mm | Standard Deviation 17.34 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period | Change at Week 12 (n=73) | -35.5 mm | Standard Deviation 25.95 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period | Change at Week 24 (n=69) | -41.5 mm | Standard Deviation 24.43 |
Secondary
Change From Baseline in SJC During the Initial Treatment Period
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in SJC During the Initial Treatment Period | Baseline (n=117) | 13.7 swollen joints | Standard Deviation 5.33 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in SJC During the Initial Treatment Period | Change at Week 4 (n=115) | -3.6 swollen joints | Standard Deviation 4.45 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in SJC During the Initial Treatment Period | Change at Week 12 (n=113) | -5.7 swollen joints | Standard Deviation 4.97 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in SJC During the Initial Treatment Period | Change at Week 24 (n=106) | -7.1 swollen joints | Standard Deviation 5.66 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in SJC During the Initial Treatment Period | Change at Week 36 (n=67) | -5.6 swollen joints | Standard Deviation 6.5 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in SJC During the Initial Treatment Period | Change at Week 48 (n=33) | -7.7 swollen joints | Standard Deviation 5.56 |
Comparison: Baseline vs Week 24p-value: <0.001Wilcoxon Signed-Rank test
Secondary
Change From Baseline in SJC During the Re-Treatment Period
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given vist.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in SJC During the Re-Treatment Period | Baseline (n=117) | 13.7 swollen joints | Standard Deviation 5.33 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in SJC During the Re-Treatment Period | Change at Week 12 (n=71) | -7.6 swollen joints | Standard Deviation 6.07 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in SJC During the Re-Treatment Period | Change at Week 24 (n=69) | -7.7 swollen joints | Standard Deviation 5.43 |
Secondary
Change From Baseline in TJC During the Initial Treatment Period
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population; n=number of participants assessed for the specific parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in TJC During the Initial Treatment Period | Baseline (n=117) | 16.1 tender joints | Standard Deviation 6.62 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in TJC During the Initial Treatment Period | Change at Week 4 (n=115) | -6.3 tender joints | Standard Deviation 5.95 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in TJC During the Initial Treatment Period | Change at Week 12 (n=113) | -7.8 tender joints | Standard Deviation 6.68 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in TJC During the Initial Treatment Period | Change at Week 24 (n=106) | -9.0 tender joints | Standard Deviation 6.42 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in TJC During the Initial Treatment Period | Change at Week 36 (n=67) | -7.4 tender joints | Standard Deviation 8.35 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in TJC During the Initial Treatment Period | Change at Week 48 (n=33) | -7.8 tender joints | Standard Deviation 8.31 |
Comparison: Baseline vs Week 24p-value: <0.001t-test, 1 sided
Secondary
Change From Baseline in TJC During the Re-Treatment Period
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in TJC During the Re-Treatment Period | Baseline (n=117) | 16.1 tender joints | Standard Deviation 6.62 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in TJC During the Re-Treatment Period | Change at Week 12 (n=71) | -9.4 tender joints | Standard Deviation 7.54 |
| Initial Treatment Period: Rituximab + MTX | Change From Baseline in TJC During the Re-Treatment Period | Change at Week 24 (n=69) | -9.7 tender joints | Standard Deviation 6.92 |
Secondary
Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period
ACR20/50/70, defined as ≥20%, 50%, or 70% improvement, respectively, compared to baseline in TJC and SJC, and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; HAQ-DI; and an acute phase reactant (ESR or CRP). If CRP was missing or not done, then ESR was used.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period | ACR70, Week 24 | 9.1 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period | ACR20, Week 12 | 54.5 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period | ACR20, Week 24 | 58.4 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period | ACR50, Week 12 | 26.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period | ACR50, Week 24 | 28.6 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period | ACR70, Week 12 | 6.5 percentage of participants |
Secondary
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period
ACR20/50/70, defined as ≥20 percent (%), 50%, or 70% improvement, respectively, compared to baseline in tender joint count (TJC) and swollen joint count (SJC), and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and an acute phase reactant (erythrocyte sedimentation rate \[ESR\] or C-Reactive Protein \[CRP\]). If CRP was missing or not done, then ESR was used.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR20, Week 4 | 31.7 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR20, Week 12 | 50.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR20, Week 24 | 54.2 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR20, Week 36 | 25.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR20, Week 48 | 15.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR50, Week 4 | 5.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR50, Week 12 | 22.5 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR50, Week 24 | 25.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR50, Week 36 | 11.7 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR50, Week 48 | 9.2 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR70, Week 4 | 0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR70, Week 12 | 4.2 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR70, Week 24 | 5.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR70, Week 36 | 5.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period | ACR70, Week 48 | 4.2 percentage of participants |
Comparison: ACR20: Week 12 versus (vs) Week 4p-value: 0.253Regression, Logistic
Comparison: ACR20: Week 24 vs Week 4p-value: 0.005Regression, Logistic
Comparison: ACR50: Week 12 vs Week 4p-value: 0.023Regression, Logistic
Comparison: ACR50: Week 24 vs. Week 4p-value: 0.001Regression, Logistic
Secondary
Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period
The EULAR response criteria were based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period | Week 12: Good | 20.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period | Week 12: Moderate | 53.2 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period | Week 12: Good/Moderate | 74.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period | Week 12: None | 22.1 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period | Week 24: Good | 19.5 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period | Week 24: Moderate | 48.1 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period | Week 24: Good/Moderate | 67.5 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period | Week 24: None | 26.0 percentage of participants |
Secondary
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period
The EULAR response criteria were based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score less than or equal to \[≤\]3.2), moderate (DAS28 score greater than \[\>\]3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 4: Good | 4.2 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 4: Moderate | 47.5 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 4: Good/Moderate | 51.7 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 4: None | 46.7 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 12: Good | 9.2 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 12: Moderate | 55.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 12: Good/Moderate | 64.2 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 12: None | 33.3 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 24: Good | 17.5 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 24: Moderate | 50.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 24: Good/Moderate | 67.5 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 24: None | 26.7 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 36: Good | 10.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 36: Moderate | 24.2 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 36: Good/Moderate | 35.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 36: None | 23.3 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 48: Good | 8.3 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 48: Moderate | 10.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 48: Good/Moderate | 19.2 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period | Week 48: None | 10.0 percentage of participants |
Comparison: Good vs Moderate vs None: Week 12 vs Week 4p-value: 0.667Regression, Logistic
Comparison: Good vs Moderate vs None: Week 24 vs Week 4p-value: <0.001Regression, Logistic
Comparison: Good/Moderate vs None: Week 12 vs Week 4p-value: 0.44Regression, Logistic
Comparison: Good/Moderate vs None: Week 24 vs Week 4p-value: 0.012Regression, Logistic
Secondary
Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary
Percentage of participants who reported an AE or SAE, a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.
Time frame: Days 1, 2, 15, and 16 and Week 48 of Re-treatment period
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary | With an SAE | 9.1 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary | With an AE | 68.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary | With a drug-related AE | 27.3 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary | With an acute infusion reaction | 13.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary | With AE leading to study drug discontinuation | 1.3 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary | With infections | 27.3 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary | With a serious infections | 2.6 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary | Who died | 0 percentage of participants |
Secondary
Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Initial Treatment Period
Complete clinical response was defined as having an ACR70 for at least 13 weeks.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Initial Treatment Period | 4.2 percentage of participants |
Secondary
Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Re-Treatment Period
Complete clinical response was defined as having an ACR70 for at least 13 weeks.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Re-Treatment Period | 1.3 percentage of participants |
Secondary
Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
Time frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period | Week 4 | 0.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period | Week 12 | 5.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period | Week 24 | 5.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period | Week 36 | 5.8 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period | Week 48 | 5.8 percentage of participants |
Secondary
Percentage of Participants With Disease Remission According to DAS28 in the Re-Treatment Period
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
Time frame: Weeks 12 and 24 of Re-treatment period
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Disease Remission According to DAS28 in the Re-Treatment Period | Week 12 | 5.0 percentage of participants |
| Initial Treatment Period: Rituximab + MTX | Percentage of Participants With Disease Remission According to DAS28 in the Re-Treatment Period | Week 24 | 4.2 percentage of participants |