Rheumatoid Arthritis
Conditions
Brief summary
This study will evaluate the efficacy and safety of various treatment and retreatment regimens of MabThera. All patients will receive concomitant methotrexate, 10-25mg once weekly either orally or parenterally. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals.
Interventions
DRUGrituximab [MabThera/Rituxan]
500mg iv in days 1 and 15, and 500mg iv on days 168 and 182
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 No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients \>=18 years of age; * RA for \>=6 months; * receiving outpatient treatment; * inadequate response to methotrexate, having received and tolerated it for \>=12 weeks, with a stable dose for \>=4 weeks.
Exclusion criteria
* rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA; * inflammatory joint disease other than RA, or other systemic autoimmune disorder; * diagnosis of juvenile arthritis, or RA before the age of 16; * previous treatment with \>1 biologic agent, any cell-depleting therapies, or concurrent treatment with any biologic agent or DMARD other than methotrexate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20) | Week 48 | ACR20 defined as overall score of ≥20 in ACR number (ACRn) calculation. Overall score defined as lowest percent improvement from baseline (BL) of following 3 measures: tender joint count (TJC; 68 joints), swollen joint count (SJC: 66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (visual analog assessment \[VAS\]), Health Assessment Questionnaire (HAQ), and C-Reactive Protein (CRP). If CRP missing, erythrocyte sedimentation rate (ESR) was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. Last observation carried forward (LOCF) for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR20 set to Non-Responder if ACRn missing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR): Adjusted Mean Change From BL at Week 48 | BL, Week 48 | DAS28 was calculated according to the following formula: DAS28 equals (=) \[0.56 multiplied by (\*) the square root (√) of TJC\] plus (+) \[0.28 \* √ of SJC\] + (0.70 \* the natural logarithm (ln) ESR in millimeters per hour (mm/h)\] + \[0.014 \* participant's global assessment of disease activity (GH)\]. DAS28-ESR ≥ 5.1 = high disease activity, DAS28-ESR less than or equal to (≤) 3.2 = low disease activity, DAS28-ESR less than (\<) 2.6 = remission. |
| Percentage of Participants With ACR 50% Improvement Criteria (ACR50) Response at Week 48 | Week 48 | ACR50 was defined as an overall score of 50 in the ACRn calculation. Overall score defined as lowest percent improvement from BL of following 3 measures: TJC (68 joints), SJC (66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (VAS), HAQ, and CRP. If CRP missing, ESR was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. LOCF for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR50 set to Non-Responder if ACRn missing. |
| Percentage of Participants With a ACR 70% Improvement Criteria (ACR70) Response at Week 48 | Week 48 | ACR70 was defined as an overall score of 70 in the ACRn calculation. The Overall score defined as lowest percent improvement from BL of following 3 measures: TJC (68 joints), SJC (66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (VAS), HAQ, and CRP. If CRP missing, ESR was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. LOCF for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR70 set to Non-Responder if ACRn missing. |
| Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Surface expression of CD19 in the absence of CD27 expression was assessed by FACS analysis as a marker of naive B lymphocyte count. |
| Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category | Week 48 | EULAR responses were categorized according to DAS28-ESR score. DAS28-ESR ≤ 3.2 at Week 48 and a change from BL to Week 48 \< -1.2 = good response, DAS28-ESR ≤ 3.2 or greater than (\>) 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 \< -0.6 and ≥ -1.2 = moderate response, DAS28-ESR \> 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 \< -1.2 = moderate response, DAS28-ESR \> 5.1 at Week 48 and a change from BL to Week 48 \< -1.2 = moderate response, DAS28-ESR ≤ 3.2 or \> 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 ≥ -0.6 = no response, DAS28-ESR \> 5.1 at Week 48 and a change from BL to Week 48 \< -0.6 and ≥ -1.2 or ≥ -0.6 = no response. |
| Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48 | BL, Week 48 | FACIT-F scores were obtained from a 13 question self-administered participant questionnaire designed to measure the degree of fatigue experienced by participants in the previous 7 days. Participants responded to the questions using a value between 0 and 4, where 0 indicated not at all and 4 indicated very much. 11 of the 13 questions were negatively stated; indicating the higher the score of the participant's response, the greater their fatigue. These questions were calculated as 4 minus the participants' response, so that a higher score indicated an improvement in health. The scores for the 2 positively stated questions were not changed. The participants' responses were summed to result in an overall score, which are scored 0 to 52 (52 = highest level of functioning). A positive change from BL indicated improvement. |
| Short-Form 36 Health Survey (SF-36) Score | BL, Week (Wk) 24 and 48 | SF-36 scores were obtained by scoring participants' responses to a 36 item questionnaire. SF-36 evaluated 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health from a range of 1 (better) to 5 (worst). The score for each section was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). These 8 aspects were summarized as physical and mental component scores. |
| Change in SF-36 Score From BL | BL, Weeks 24 and 48 | SF-36 scores were obtained by scoring participants' responses to a 36 item questionnaire. SF-36 evaluated 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health from a range of 1 (better) to 5 (worst). The score for each section was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). These 8 aspects were summarized as physical and mental component scores. |
| Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL) | Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment). | Cfirst values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2. |
| Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL | Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment). | Csecond values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2. |
| Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days | Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment). | t1/2 values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2. |
| Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL) | BL | Surface expression of CD19 was assessed by fluorescence-activated cell sorting (FACS) analysis as a marker of absolute B lymphocyte count. |
| Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | BL, Days 1 and 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Surface expression of CD19 was assessed by FACS analysis as a marker of absolute B lymphocyte count. The LLN was defined as \< 80 cells/µL. |
| Peripheral CD20+ B Cell Count in Cells/µL | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Surface expression of CD20 was assessed by FACS analysis as a marker of mature and memory B lymphocyte count. |
| Peripheral CD22+ B Cell Count in Cells/µL | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Surface expression of CD22 was assessed by FACS analysis as a marker of mature lymphocyte count. |
| Peripheral CD19+CD27+ B Cell Count in Cells/µL | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Simultaneous surface expression of CD19 and CD27 was assessed by FACS analysis as a marker of memory B lymphocyte count. |
| Change From BL in Peripheral CD3+ T Cell Count | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Surface expression of CD3 was assessed by FACS analysis as a marker of absolute T lymphocyte count. The normal range of CD3+ T cells was defined as 723-2737 cells/µL. |
| Peripheral CD4+ T Cell Count in Cells/µL | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Surface expression of CD4 was assessed by FACS analysis as a marker of T helper cell count. The normal range of CD4+ T cells was defined as 404-1612 cells/µL. |
| Peripheral CD3+ T Cell Count in Cells/µL | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Surface expression of CD3 was assessed by FACS analysis as a marker of absolute T lymphocyte count. The normal range of CD3+ T cells was defined as 723-2737 cells/µL. |
| Peripheral CD8+ T Cell Count in Cells/µL | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Surface expression of CD8 was assessed by FACS analysis as a marker of cytotoxic T lymphocyte count. The normal range of CD8+ T cells was defined as 220-1129 cells/µL. |
| Change From BL in Peripheral CD8+ Cell Count | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Surface expression of CD8 was assessed by FACS analysis as a marker of cytotoxic T lymphocyte count. The normal range of CD8+ T cells was defined as 220-1129 cells/µL. |
| Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Simultaneous surface expression of CD16 and CD56 was assessed by FACS analysis as a marker of NK cell count. |
| Change From BL in Peripheral CD16+56+ Cell Count | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Simultaneous surface expression of CD16 and CD56 was assessed by FACS analysis as a marker of NK cell count. |
| Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, Weeks 24 and 48 | The LLNs for total Ig, IgA, IgG, and IgM were defined as 6.75 grams per liter (g/L), 0.70 g/L, 65 g/L, and 0.40 g/L, respectively. |
| Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative | BL, Weeks 8, 24, and 48 | Percentage of participants who were RF seropositive at BL who became RF seronegative over the course of the study. RF seropositive status was defined as RF ≥ 20 international units (IU) per mL. RF seronegative status was defined as RF \< 20 IU/mL. |
| Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL) | BL | — |
| Change From BL in Anti-CCP Antibody Titers in U/mL | Weeks 8, 24, and 48 | — |
| Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | The LLN for C3 protein was defined as \<0.9 grams per liter (g/L). |
| Change From BL in Complement C3 Protein Level in g/L | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | The LLN of C3 protein was defined as \<0.9 g/L. |
| Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | — |
| Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | The LLN of C4 protein was defined as \< 0.1 g/L. |
| Change From BL in Complement C4 Protein Level in g/L | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | — |
| Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | — |
| Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | BL, Weeks 24 and 48 | A participant was defined as being HACA positive if the HACA serum level was ≥ 5 relative units (RU) per mL and the physician comment read that participant was immunodepletable with rituximab. |
| Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | BL, Weeks 24 and 48 | ANA titers were obtained by the following serum dilution schema: negative = negative, borderline = 1 diluted to (:) 40 or 1:80, and positive ≥ 1:160. The change categories were defined for the change from BL to Weeks 24 and 48 according to this schema. Negative to borderline was defined as any change from negative to borderline as no dilution is given for negative results. Negative to positive was defined as at least a two-fold positive change in dilution from BL. Borderline to negative was defined as any change from borderline to negative as no dilution is given for negative results. Borderline to positive was defined as at least a two-fold positive change in dilution from BL. Positive to borderline was defined as at least a two-fold negative change in dilution from BL. Positive to negative was defined as at least a two-fold negative change in dilution from BL. Unchanged was defined as any difference in dilution less than two-fold. |
| Percentage of Participants With Positive Recall Antigen Antibody Titers | BL, Weeks 24 and 48 | A positive titer result to recall antigens was defined as a serum antibody level equal to or above the following protective levels: tetanus toxoid ≥ 0.1 IU/mL, influenza A \> 12 U/mL, influenza B \> 12 U/mL, and streptococcus (S.) pneumococcus ≥ 1.0 mg/L. |
| Change From BL in Peripheral CD4+ T Cell Count | BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48 | Surface expression of CD4 was assessed by FACS analysis as a marker of T helper cell count. The normal range of CD4+ T cells was defined as 404-1612 cells/µL. |
Countries
Australia, Belgium, Brazil, Canada, China, Finland, France, Germany, Hungary, Italy, Netherlands, New Zealand, Slovakia, South Africa, Spain, Taiwan, Thailand, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Low Dose + Methotrexate Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. | 134 |
| Rituximab Escalated Dose + Methotrexate Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. | 119 |
| Rituximab High Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. | 93 |
| Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment. | 6 |
| Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment. | 25 |
| Total | 377 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 | 1 | 1 | 0 |
| Overall Study | Lack of Efficacy | 4 | 4 | 2 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 5 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Rituximab Low Dose + Methotrexate | Rituximab Escalated Dose + Methotrexate | Rituximab High Dose + Methotrexate | Rituximab/Placebo + Methotrexate | Rituximab Decreased Dose + Methotrexate | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 53.58 years STANDARD_DEVIATION 12.805 | 52.32 years STANDARD_DEVIATION 12.115 | 51.26 years STANDARD_DEVIATION 12.179 | 51.83 years STANDARD_DEVIATION 6.274 | 52.32 years STANDARD_DEVIATION 8.882 | 52.48 years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 110 Participants | 90 Participants | 77 Participants | 4 Participants | 16 Participants | 297 Participants |
| Sex: Female, Male Male | 24 Participants | 29 Participants | 16 Participants | 2 Participants | 9 Participants | 80 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 120 / 134 | 103 / 119 | 88 / 93 | 6 / 6 | 22 / 25 |
| serious Total, serious adverse events | 15 / 134 | 21 / 119 | 16 / 93 | 1 / 6 | 3 / 25 |
Outcome results
Primary
Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20)
ACR20 defined as overall score of ≥20 in ACR number (ACRn) calculation. Overall score defined as lowest percent improvement from baseline (BL) of following 3 measures: tender joint count (TJC; 68 joints), swollen joint count (SJC: 66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (visual analog assessment \[VAS\]), Health Assessment Questionnaire (HAQ), and C-Reactive Protein (CRP). If CRP missing, erythrocyte sedimentation rate (ESR) was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. Last observation carried forward (LOCF) for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR20 set to Non-Responder if ACRn missing
Time frame: Week 48
Population: ITT-M2 population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20) | 64.2 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20) | 63.9 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20) | 72.0 percentage of participants |
p-value: 0.815695% CI: [-0.13, 0.1]Cochran-Mantel-Haenszel
p-value: 0.241995% CI: [-0.05, 0.19]Cochran-Mantel-Haenszel
Secondary
Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL)
Time frame: BL
Population: SAP. 3, 3, and 2 participants were not analyzed for this outcome measure from the Low Dose, Escalated Dose, and High Dose, groups, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL) | 205.39 U/mL | Standard Deviation 374.203 |
| Rituximab Escalated Dose + Methotrexate | Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL) | 179.01 U/mL | Standard Deviation 255.251 |
| Rituximab High Dose + Methotrexate | Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL) | 263.61 U/mL | Standard Deviation 477.554 |
| Rituximab/Placebo + Methotrexate | Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL) | 184.77 U/mL | Standard Deviation 304.169 |
| Rituximab Decreased Dose + Methotrexate | Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL) | 310.94 U/mL | Standard Deviation 334.849 |
Secondary
Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | BL Postdose (n=27,21,22) | -326.9 g/L | Standard Deviation 3990.88 |
| Rituximab Low Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | Day 15 Predose (n=18,10,14) | -1176.8 g/L | Standard Deviation 4494.98 |
| Rituximab Low Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | Day 15 Postdose (n=18,10,14) | -1117.7 g/L | Standard Deviation 4347.64 |
| Rituximab Low Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | Wk 4 (n=14,9,11) | 103.9 g/L | Standard Deviation 749.79 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | Wk 4 (n=14,9,11) | -124.2 g/L | Standard Deviation 921.23 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | BL Postdose (n=27,21,22) | -92.8 g/L | Standard Deviation 836.55 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | Day 15 Postdose (n=18,10,14) | -285.4 g/L | Standard Deviation 403.44 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | Day 15 Predose (n=18,10,14) | -17.1 g/L | Standard Deviation 389.94 |
| Rituximab High Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | Wk 4 (n=14,9,11) | -142.4 g/L | Standard Deviation 504.95 |
| Rituximab High Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | Day 15 Predose (n=18,10,14) | 1054.1 g/L | Standard Deviation 5409.76 |
| Rituximab High Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | Day 15 Postdose (n=18,10,14) | -164.9 g/L | Standard Deviation 740.91 |
| Rituximab High Dose + Methotrexate | Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L | BL Postdose (n=27,21,22) | 1319.9 g/L | Standard Deviation 5104.05 |
Secondary
Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | BL Postdose (n=26,21,22) | -1424.3 g/L | Standard Deviation 3801.86 |
| Rituximab Low Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | Day 15 Predose (n=18,10,14) | -971.3 g/L | Standard Deviation 3149.08 |
| Rituximab Low Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | Day 15 Postdose (n=18,10,14) | -1885.3 g/L | Standard Deviation 2458.08 |
| Rituximab Low Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | Wk 4 (n=14,8,10) | 629.8 g/L | Standard Deviation 5993.96 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | Wk 4 (n=14,8,10) | 260.4 g/L | Standard Deviation 1450.4 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | BL Postdose (n=26,21,22) | -480.1 g/L | Standard Deviation 3137.12 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | Day 15 Postdose (n=18,10,14) | -333.0 g/L | Standard Deviation 706.11 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | Day 15 Predose (n=18,10,14) | 3004.9 g/L | Standard Deviation 10300.68 |
| Rituximab High Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | Wk 4 (n=14,8,10) | 109.8 g/L | Standard Deviation 1566.68 |
| Rituximab High Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | Day 15 Predose (n=18,10,14) | 3.5 g/L | Standard Deviation 1832.62 |
| Rituximab High Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | Day 15 Postdose (n=18,10,14) | -1011.1 g/L | Standard Deviation 1574.01 |
| Rituximab High Dose + Methotrexate | Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L | BL Postdose (n=26,21,22) | -3749.1 g/L | Standard Deviation 13498.79 |
Secondary
Change From BL in Anti-CCP Antibody Titers in U/mL
Time frame: Weeks 8, 24, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 8 (n=127,112,85,6,24) | -42.97 U/mL | Standard Deviation 94.873 |
| Rituximab Low Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 48 (n=116,102,87,4,22) | -72.99 U/mL | Standard Deviation 151.086 |
| Rituximab Low Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 24 (n=117,107,82,4,24) | -68.23 U/mL | Standard Deviation 158.951 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 24 (n=117,107,82,4,24) | -56.76 U/mL | Standard Deviation 144.256 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 8 (n=127,112,85,6,24) | -46.84 U/mL | Standard Deviation 140.589 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 48 (n=116,102,87,4,22) | -82.51 U/mL | Standard Deviation 223.577 |
| Rituximab High Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 24 (n=117,107,82,4,24) | -72.96 U/mL | Standard Deviation 219.466 |
| Rituximab High Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 8 (n=127,112,85,6,24) | -70.39 U/mL | Standard Deviation 265.694 |
| Rituximab High Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 48 (n=116,102,87,4,22) | -127.21 U/mL | Standard Deviation 307.981 |
| Rituximab/Placebo + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 8 (n=127,112,85,6,24) | -33.80 U/mL | Standard Deviation 58.443 |
| Rituximab/Placebo + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 48 (n=116,102,87,4,22) | -28.98 U/mL | Standard Deviation 42.881 |
| Rituximab/Placebo + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 24 (n=117,107,82,4,24) | -70.33 U/mL | Standard Deviation 149.881 |
| Rituximab Decreased Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 24 (n=117,107,82,4,24) | -64.32 U/mL | Standard Deviation 89.763 |
| Rituximab Decreased Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 8 (n=127,112,85,6,24) | -18.67 U/mL | Standard Deviation 54.228 |
| Rituximab Decreased Dose + Methotrexate | Change From BL in Anti-CCP Antibody Titers in U/mL | Wk 48 (n=116,102,87,4,22) | -81.57 U/mL | Standard Deviation 167.012 |
Secondary
Change From BL in Complement C3 Protein Level in g/L
The LLN of C3 protein was defined as \<0.9 g/L.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | BL Postdose (n=119,102,84) | -0.0469 g/L | Standard Deviation 0.17761 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Predose (n=120,105,80) | -0.0423 g/L | Standard Deviation 0.20915 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Postdose (n=118,104,79) | -0.0413 g/L | Standard Deviation 0.18365 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Wk 4 (n=118,105,78) | -0.0137 g/L | Standard Deviation 0.22743 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | BL Pre Retreatment (n=115,98,83) | -0.0621 g/L | Standard Deviation 0.21365 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | BL Post Retreatment (n=113,97,78) | -0.0889 g/L | Standard Deviation 0.21974 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Pre Retreatment (n=115,97,81) | -0.0953 g/L | Standard Deviation 0.20329 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Post Retreatment (n=113,99,82) | -0.1048 g/L | Standard Deviation 0.20255 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Postdose (n=118,104,79) | -0.0235 g/L | Standard Deviation 0.19255 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Pre Retreatment (n=115,97,81) | -0.0580 g/L | Standard Deviation 0.26221 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Wk 4 (n=118,105,78) | 0.0279 g/L | Standard Deviation 0.20724 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | BL Pre Retreatment (n=115,98,83) | -0.0225 g/L | Standard Deviation 0.20578 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | BL Post Retreatment (n=113,97,78) | -0.0673 g/L | Standard Deviation 0.2115 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | BL Postdose (n=119,102,84) | -0.0563 g/L | Standard Deviation 0.16277 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Predose (n=120,105,80) | -0.0143 g/L | Standard Deviation 0.17514 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Post Retreatment (n=113,99,82) | -0.0979 g/L | Standard Deviation 0.23505 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Postdose (n=118,104,79) | -0.1094 g/L | Standard Deviation 0.2186 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Predose (n=120,105,80) | -0.0773 g/L | Standard Deviation 0.17876 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | BL Postdose (n=119,102,84) | -0.0802 g/L | Standard Deviation 0.12774 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Wk 4 (n=118,105,78) | -0.0596 g/L | Standard Deviation 0.18186 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Pre Retreatment (n=115,97,81) | -0.1374 g/L | Standard Deviation 0.19296 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | BL Post Retreatment (n=113,97,78) | -0.1395 g/L | Standard Deviation 0.21823 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | BL Pre Retreatment (n=115,98,83) | -0.0864 g/L | Standard Deviation 0.19814 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C3 Protein Level in g/L | Day 15 Post Retreatment (n=113,99,82) | -0.1533 g/L | Standard Deviation 0.21412 |
Secondary
Change From BL in Complement C4 Protein Level in g/L
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | BL Postdose (n=119,102,84) | -0.0187 g/L | Standard Deviation 0.0495 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Predose (n=120,105,80) | -0.0139 g/L | Standard Deviation 0.06109 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Postdose (n=117,104,79) | -0.0126 g/L | Standard Deviation 0.0533 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Wk 4 (n=118,104,78) | 0.0020 g/L | Standard Deviation 0.06441 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | BL Pre Retreatment (n=115,98,83) | 0.0046 g/L | Standard Deviation 0.06671 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | BL Post Retreatment (n=113,97,77) | -0.0017 g/L | Standard Deviation 0.05998 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Pre Retreatment (n=115,97,81) | -0.0049 g/L | Standard Deviation 0.0612 |
| Rituximab Low Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Post Retreatment (n=113,99,82) | -0.0079 g/L | Standard Deviation 0.06431 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Postdose (n=117,104,79) | -0.0071 g/L | Standard Deviation 0.04819 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Pre Retreatment (n=115,97,81) | 0.0138 g/L | Standard Deviation 0.12093 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Wk 4 (n=118,104,78) | 0.0069 g/L | Standard Deviation 0.05476 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | BL Pre Retreatment (n=115,98,83) | 0.0214 g/L | Standard Deviation 0.06848 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | BL Post Retreatment (n=113,97,77) | 0.0064 g/L | Standard Deviation 0.05432 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | BL Postdose (n=119,102,84) | -0.0170 g/L | Standard Deviation 0.04048 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Predose (n=120,105,80) | -0.0089 g/L | Standard Deviation 0.04479 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Post Retreatment (n=113,99,82) | -0.0014 g/L | Standard Deviation 0.05706 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Postdose (n=117,104,79) | -0.0320 g/L | Standard Deviation 0.04947 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Predose (n=120,105,80) | -0.0230 g/L | Standard Deviation 0.0433 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | BL Postdose (n=119,102,84) | -0.0220 g/L | Standard Deviation 0.0271 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Wk 4 (n=118,104,78) | -0.0020 g/L | Standard Deviation 0.08212 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Pre Retreatment (n=115,97,81) | -0.0142 g/L | Standard Deviation 0.05015 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | BL Post Retreatment (n=113,97,77) | -0.0068 g/L | Standard Deviation 0.05746 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | BL Pre Retreatment (n=115,98,83) | 0.0128 g/L | Standard Deviation 0.12884 |
| Rituximab High Dose + Methotrexate | Change From BL in Complement C4 Protein Level in g/L | Day 15 Post Retreatment (n=113,99,82) | -0.0168 g/L | Standard Deviation 0.05079 |
Secondary
Change From BL in Peripheral CD16+56+ Cell Count
Simultaneous surface expression of CD16 and CD56 was assessed by FACS analysis as a marker of NK cell count.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 28 (n=115,94,84) | 30.3 cells/µL | Standard Deviation 103.95 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 8 (n=121,105,87) | 25.7 cells/µL | Standard Deviation 88.56 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 40 (n=113,96,81) | 53.6 cells/µL | Standard Deviation 125.06 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 24 (n=109,100,82) | 13.2 cells/µL | Standard Deviation 89.73 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 16 (n=117,105,88) | 29.1 cells/µL | Standard Deviation 96.16 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | BL Postdose (n=115,106,82) | -72.2 cells/µL | Standard Deviation 92.33 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Day 15 Postdose (n=116,102,86) | -0.2 cells/µL | Standard Deviation 91.95 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Day 15 Predose (n=122,107,84) | 4.0 cells/µL | Standard Deviation 72.79 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 32 (n=116,99,85) | 41.0 cells/µL | Standard Deviation 109.6 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 4 (n=122,105,84) | 8.8 cells/µL | Standard Deviation 81.85 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 48 (n=110,96,80) | 34.7 cells/µL | Standard Deviation 94.33 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 16 (n=117,105,88) | 17.2 cells/µL | Standard Deviation 73.16 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | BL Postdose (n=115,106,82) | -60.5 cells/µL | Standard Deviation 93.63 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Day 15 Predose (n=122,107,84) | 4.5 cells/µL | Standard Deviation 74.48 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Day 15 Postdose (n=116,102,86) | 8.8 cells/µL | Standard Deviation 104.11 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 4 (n=122,105,84) | 15.6 cells/µL | Standard Deviation 80.56 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 8 (n=121,105,87) | 15.1 cells/µL | Standard Deviation 82.02 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 24 (n=109,100,82) | 28.8 cells/µL | Standard Deviation 86.61 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 28 (n=115,94,84) | 29.5 cells/µL | Standard Deviation 95.65 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 32 (n=116,99,85) | 39.8 cells/µL | Standard Deviation 90.37 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 40 (n=113,96,81) | 38.8 cells/µL | Standard Deviation 101.55 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 48 (n=110,96,80) | 39.8 cells/µL | Standard Deviation 87.49 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 40 (n=113,96,81) | 40.6 cells/µL | Standard Deviation 90.44 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 28 (n=115,94,84) | 24.8 cells/µL | Standard Deviation 81.95 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Day 15 Postdose (n=116,102,86) | -2.7 cells/µL | Standard Deviation 84.49 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | BL Postdose (n=115,106,82) | -83.2 cells/µL | Standard Deviation 84.98 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 32 (n=116,99,85) | 19.0 cells/µL | Standard Deviation 82.51 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Day 15 Predose (n=122,107,84) | -1.4 cells/µL | Standard Deviation 64.87 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 16 (n=117,105,88) | 12.3 cells/µL | Standard Deviation 80.04 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 8 (n=121,105,87) | 4.8 cells/µL | Standard Deviation 61.94 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 48 (n=110,96,80) | 38.9 cells/µL | Standard Deviation 85.59 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 24 (n=109,100,82) | 8.0 cells/µL | Standard Deviation 76.78 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD16+56+ Cell Count | Wk 4 (n=122,105,84) | 3.4 cells/µL | Standard Deviation 79.93 |
Secondary
Change From BL in Peripheral CD3+ T Cell Count
Surface expression of CD3 was assessed by FACS analysis as a marker of absolute T lymphocyte count. The normal range of CD3+ T cells was defined as 723-2737 cells/µL.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 28 (n=115,94,84) | 41.4 cells/µL | Standard Deviation 599.47 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 8 (n=121,105,87) | 3.4 cells/µL | Standard Deviation 548.8 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 40 (n=113,96,81) | 33.5 cells/µL | Standard Deviation 517.7 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 24 (n=109,100,82) | 78.1 cells/µL | Standard Deviation 511.99 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 16 (n=117,105,88) | -24.5 cells/µL | Standard Deviation 517.71 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | BL Postdose (n=115,106,82) | -1000.6 cells/µL | Standard Deviation 576.77 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Day 15 Postdose (n=116,102,86) | -952.6 cells/µL | Standard Deviation 572.95 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Day 15 Predose (n=122,107,84) | 25.2 cells/µL | Standard Deviation 478.94 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 32 (n=116,99,85) | 47.9 cells/µL | Standard Deviation 557.67 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 4 (n=122,105,84) | -31.9 cells/µL | Standard Deviation 427.92 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 48 (n=110,96,80) | -9.4 cells/µL | Standard Deviation 538.12 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 16 (n=117,105,88) | 81.8 cells/µL | Standard Deviation 436.08 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | BL Postdose (n=115,106,82) | -968.8 cells/µL | Standard Deviation 539.8 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Day 15 Predose (n=122,107,84) | 40.8 cells/µL | Standard Deviation 435.72 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Day 15 Postdose (n=116,102,86) | -897.3 cells/µL | Standard Deviation 535.33 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 4 (n=122,105,84) | -19.6 cells/µL | Standard Deviation 450.67 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 8 (n=121,105,87) | 98.8 cells/µL | Standard Deviation 496.83 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 24 (n=109,100,82) | 47.7 cells/µL | Standard Deviation 448.72 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 28 (n=115,94,84) | 20.1 cells/µL | Standard Deviation 379.99 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 32 (n=116,99,85) | 51.2 cells/µL | Standard Deviation 412.36 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 40 (n=113,96,81) | 65.1 cells/µL | Standard Deviation 511.46 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 48 (n=110,96,80) | 20.3 cells/µL | Standard Deviation 431.58 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 40 (n=113,96,81) | -12.7 cells/µL | Standard Deviation 421.39 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 28 (n=115,94,84) | -0.4 cells/µL | Standard Deviation 488.79 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Day 15 Postdose (n=116,102,86) | -965.9 cells/µL | Standard Deviation 500.78 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | BL Postdose (n=115,106,82) | -1065.4 cells/µL | Standard Deviation 513.18 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 32 (n=116,99,85) | -18.4 cells/µL | Standard Deviation 439.47 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Day 15 Predose (n=122,107,84) | 34.0 cells/µL | Standard Deviation 463.99 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 16 (n=117,105,88) | -47.4 cells/µL | Standard Deviation 506.89 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 8 (n=121,105,87) | -23.6 cells/µL | Standard Deviation 429.32 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 48 (n=110,96,80) | -12.4 cells/µL | Standard Deviation 502.2 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 24 (n=109,100,82) | -0.8 cells/µL | Standard Deviation 444.81 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD3+ T Cell Count | Wk 4 (n=122,105,84) | -53.3 cells/µL | Standard Deviation 476.03 |
Secondary
Change From BL in Peripheral CD4+ T Cell Count
Surface expression of CD4 was assessed by FACS analysis as a marker of T helper cell count. The normal range of CD4+ T cells was defined as 404-1612 cells/µL.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 28 (n=115,94,84) | 42.8 cells/µL | Standard Deviation 446.65 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 8 (n=121,105,87) | 7.9 cells/µL | Standard Deviation 418.85 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 40 (n=113,96,81) | 14.9 cells/µL | Standard Deviation 375.97 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 24 (n=109,100,82) | 72.6 cells/µL | Standard Deviation 395.29 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 16 (n=117,105,88) | -24.3 cells/µL | Standard Deviation 377.76 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | BL Postdose (n=115,106,82) | -744.6 cells/µL | Standard Deviation 454.55 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Day 15 Postdose (n=116,102,86) | -732.2 cells/µL | Standard Deviation 449.99 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Day 15 Predose (n=122,107,84) | 24.3 cells/µL | Standard Deviation 355.22 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 32 (n=116,99,85) | 38.4 cells/µL | Standard Deviation 419.78 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 4 (n=122,105,84) | -16.1 cells/µL | Standard Deviation 330.2 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 48 (n=110,96,80) | -8.5 cells/µL | Standard Deviation 399.48 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 16 (n=117,105,88) | 64.0 cells/µL | Standard Deviation 349.16 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | BL Postdose (n=115,106,82) | -738.1 cells/µL | Standard Deviation 393.02 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Day 15 Predose (n=122,107,84) | 38.9 cells/µL | Standard Deviation 306.89 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Day 15 Postdose (n=116,102,86) | -696.5 cells/µL | Standard Deviation 392.37 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 4 (n=122,105,84) | -4.2 cells/µL | Standard Deviation 345.57 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 8 (n=121,105,87) | 84.1 cells/µL | Standard Deviation 370.64 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 24 (n=109,100,82) | 37.3 cells/µL | Standard Deviation 312.15 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 28 (n=115,94,84) | 13.5 cells/µL | Standard Deviation 276.55 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 32 (n=116,99,85) | 39.2 cells/µL | Standard Deviation 305.18 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 40 (n=113,96,81) | 39.5 cells/µL | Standard Deviation 356.89 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 48 (n=110,96,80) | 15.2 cells/µL | Standard Deviation 320.98 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 40 (n=113,96,81) | -6.4 cells/µL | Standard Deviation 331.87 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 28 (n=115,94,84) | 7.4 cells/µL | Standard Deviation 377.73 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Day 15 Postdose (n=116,102,86) | -749.4 cells/µL | Standard Deviation 401.01 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | BL Postdose (n=115,106,82) | -801.2 cells/µL | Standard Deviation 416.45 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 32 (n=116,99,85) | -8.4 cells/µL | Standard Deviation 337.42 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Day 15 Predose (n=122,107,84) | 36.0 cells/µL | Standard Deviation 359.92 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 16 (n=117,105,88) | -33.4 cells/µL | Standard Deviation 407.52 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 8 (n=121,105,87) | -4.4 cells/µL | Standard Deviation 343.31 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 48 (n=110,96,80) | -10.1 cells/µL | Standard Deviation 366.44 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 24 (n=109,100,82) | -0.7 cells/µL | Standard Deviation 336.19 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD4+ T Cell Count | Wk 4 (n=122,105,84) | -36.2 cells/µL | Standard Deviation 368.83 |
Secondary
Change From BL in Peripheral CD8+ Cell Count
Surface expression of CD8 was assessed by FACS analysis as a marker of cytotoxic T lymphocyte count. The normal range of CD8+ T cells was defined as 220-1129 cells/µL.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 28 (n=115,94,84) | -3.5 cells/µL | Standard Deviation 183.31 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 8 (n=121,105,87) | -6.6 cells/µL | Standard Deviation 157.14 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 40 (n=113,96,81) | 11.9 cells/µL | Standard Deviation 174.03 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 24 (n=109,100,82) | 2.1 cells/µL | Standard Deviation 150.31 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 16 (n=117,105,88) | -1.2 cells/µL | Standard Deviation 176.58 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | BL Postdose (n=115,106,82) | -256.2 cells/µL | Standard Deviation 190.92 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Day 15 Postdose (n=116,102,86) | -222.4 cells/µL | Standard Deviation 180.5 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Day 15 Predose (n=122,107,84) | -1.5 cells/µL | Standard Deviation 140.66 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 32 (n=116,99,85) | 3.6 cells/µL | Standard Deviation 163.2 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 4 (n=122,105,84) | -17.3 cells/µL | Standard Deviation 127.14 |
| Rituximab Low Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 48 (n=110,96,80) | -6.1 cells/µL | Standard Deviation 168.67 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 16 (n=117,105,88) | 18.0 cells/µL | Standard Deviation 117.74 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | BL Postdose (n=115,106,82) | -229.0 cells/µL | Standard Deviation 183.97 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Day 15 Predose (n=122,107,84) | 2.6 cells/µL | Standard Deviation 167.12 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Day 15 Postdose (n=116,102,86) | -201.4 cells/µL | Standard Deviation 176.3 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 4 (n=122,105,84) | -18.0 cells/µL | Standard Deviation 128.02 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 8 (n=121,105,87) | 16.3 cells/µL | Standard Deviation 148.14 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 24 (n=109,100,82) | 14.3 cells/µL | Standard Deviation 160.58 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 28 (n=115,94,84) | 7.2 cells/µL | Standard Deviation 139.69 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 32 (n=116,99,85) | 11.6 cells/µL | Standard Deviation 144.92 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 40 (n=113,96,81) | 22.3 cells/µL | Standard Deviation 197.32 |
| Rituximab Escalated Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 48 (n=110,96,80) | 2.2 cells/µL | Standard Deviation 143.87 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 40 (n=113,96,81) | -8.5 cells/µL | Standard Deviation 112.07 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 28 (n=115,94,84) | -7.3 cells/µL | Standard Deviation 130.24 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Day 15 Postdose (n=116,102,86) | -215.5 cells/µL | Standard Deviation 140.77 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | BL Postdose (n=115,106,82) | -262.3 cells/µL | Standard Deviation 148.57 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 32 (n=116,99,85) | -8.6 cells/µL | Standard Deviation 129.83 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Day 15 Predose (n=122,107,84) | -5.0 cells/µL | Standard Deviation 122.68 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 16 (n=117,105,88) | -16.3 cells/µL | Standard Deviation 114.9 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 8 (n=121,105,87) | -21.3 cells/µL | Standard Deviation 101.94 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 48 (n=110,96,80) | -10.1 cells/µL | Standard Deviation 150.14 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 24 (n=109,100,82) | 0.4 cells/µL | Standard Deviation 130.37 |
| Rituximab High Dose + Methotrexate | Change From BL in Peripheral CD8+ Cell Count | Wk 4 (n=122,105,84) | -17.6 cells/µL | Standard Deviation 124.74 |
Secondary
Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48
FACIT-F scores were obtained from a 13 question self-administered participant questionnaire designed to measure the degree of fatigue experienced by participants in the previous 7 days. Participants responded to the questions using a value between 0 and 4, where 0 indicated not at all and 4 indicated very much. 11 of the 13 questions were negatively stated; indicating the higher the score of the participant's response, the greater their fatigue. These questions were calculated as 4 minus the participants' response, so that a higher score indicated an improvement in health. The scores for the 2 positively stated questions were not changed. The participants' responses were summed to result in an overall score, which are scored 0 to 52 (52 = highest level of functioning). A positive change from BL indicated improvement.
Time frame: BL, Week 48
Population: ITT-M2 population. 9, 4, 2, and 1 participants were not evaluated for this outcome measure from the Low Dose, Escalated Dose, High Dose, and Decreased Dose groups, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48 | 6.605 score on a scale | Standard Deviation 10.1529 |
| Rituximab Escalated Dose + Methotrexate | Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48 | 8.109 score on a scale | Standard Deviation 10.2876 |
| Rituximab High Dose + Methotrexate | Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48 | 8.364 score on a scale | Standard Deviation 9.8368 |
| Rituximab/Placebo + Methotrexate | Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48 | 2.000 score on a scale | Standard Deviation 16.025 |
| Rituximab Decreased Dose + Methotrexate | Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48 | 6.192 score on a scale | Standard Deviation 12.0081 |
Secondary
Change in SF-36 Score From BL
SF-36 scores were obtained by scoring participants' responses to a 36 item questionnaire. SF-36 evaluated 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health from a range of 1 (better) to 5 (worst). The score for each section was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). These 8 aspects were summarized as physical and mental component scores.
Time frame: BL, Weeks 24 and 48
Population: ITT-M2 population, n = number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Mental Health Score: Wk 24 (n=115,107,85) | 5.173 score on a scale | Standard Deviation 10.516 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Bodily Pain Score: Wk 48 (n=116,101,87) | 9.815 score on a scale | Standard Deviation 9.4616 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | General Health Score: Wk 24 (n=112,108,85) | 4.941 score on a scale | Standard Deviation 8.8122 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | General Health Score: Wk 48 (n=115,100,87) | 6.470 score on a scale | Standard Deviation 8.9736 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Bodily Pain Score: Wk 24 (n=115,106,85) | 8.180 score on a scale | Standard Deviation 9.7621 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Mental Health Score: Wk 48 (n=116,101,86) | 6.607 score on a scale | Standard Deviation 10.6356 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Physical Functioning Score: Wk 24 (n=111,108,85) | 5.517 score on a scale | Standard Deviation 7.6418 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Physical Functioning Score: Wk 48 (n=114,102,88) | 6.529 score on a scale | Standard Deviation 8.6382 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Emotional Role Score: Wk 24 (n=113,108,85) | 5.951 score on a scale | Standard Deviation 11.9256 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Emotional Role Score: Wk 48 (n=114,101,86) | 6.445 score on a scale | Standard Deviation 14.0187 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Physical Role Score: Wk 24 (n=113,108,84) | 6.473 score on a scale | Standard Deviation 9.1079 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Physical Role Score: Wk 48 (n=115,101,87) | 7.347 score on a scale | Standard Deviation 10.0663 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Social Functioning Score: Wk 24 (n=115,108,86 | 5.786 score on a scale | Standard Deviation 9.8861 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Social Functioning Score: Wk 48 (n=116,102,88) | 7.382 score on a scale | Standard Deviation 10.9376 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Vitality Score: Wk 24 (n=115,108,86) | 6.796 score on a scale | Standard Deviation 10.7057 |
| Rituximab Low Dose + Methotrexate | Change in SF-36 Score From BL | Vitality Score: Wk 48 (n=116,102,86) | 9.088 score on a scale | Standard Deviation 10.6821 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Mental Health Score: Wk 48 (n=116,101,86) | 4.979 score on a scale | Standard Deviation 12.3225 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Physical Functioning Score: Wk 24 (n=111,108,85) | 6.261 score on a scale | Standard Deviation 8.2243 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Physical Functioning Score: Wk 48 (n=114,102,88) | 6.318 score on a scale | Standard Deviation 9.8785 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Social Functioning Score: Wk 48 (n=116,102,88) | 7.807 score on a scale | Standard Deviation 11.188 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Emotional Role Score: Wk 24 (n=113,108,85) | 4.571 score on a scale | Standard Deviation 12.5182 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Emotional Role Score: Wk 48 (n=114,101,86) | 6.350 score on a scale | Standard Deviation 12.4357 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Vitality Score: Wk 48 (n=116,102,86) | 7.479 score on a scale | Standard Deviation 10.235 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Physical Role Score: Wk 24 (n=113,108,84) | 5.994 score on a scale | Standard Deviation 9.7472 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Bodily Pain Score: Wk 24 (n=115,106,85) | 7.914 score on a scale | Standard Deviation 8.7302 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Vitality Score: Wk 24 (n=115,108,86) | 6.495 score on a scale | Standard Deviation 10.2488 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Bodily Pain Score: Wk 48 (n=116,101,87) | 9.323 score on a scale | Standard Deviation 9.3335 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Physical Role Score: Wk 48 (n=115,101,87) | 7.493 score on a scale | Standard Deviation 9.8317 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | General Health Score: Wk 24 (n=112,108,85) | 4.996 score on a scale | Standard Deviation 8.7345 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | General Health Score: Wk 48 (n=115,100,87) | 6.340 score on a scale | Standard Deviation 8.9124 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Mental Health Score: Wk 24 (n=115,107,85) | 4.138 score on a scale | Standard Deviation 11.5165 |
| Rituximab Escalated Dose + Methotrexate | Change in SF-36 Score From BL | Social Functioning Score: Wk 24 (n=115,108,86 | 7.070 score on a scale | Standard Deviation 11.1663 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Physical Role Score: Wk 24 (n=113,108,84) | 6.385 score on a scale | Standard Deviation 9.6101 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Mental Health Score: Wk 48 (n=116,101,86) | 4.939 score on a scale | Standard Deviation 11.0695 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Social Functioning Score: Wk 24 (n=115,108,86 | 6.722 score on a scale | Standard Deviation 9.8518 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | General Health Score: Wk 24 (n=112,108,85) | 4.812 score on a scale | Standard Deviation 8.1955 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Physical Functioning Score: Wk 24 (n=111,108,85) | 7.081 score on a scale | Standard Deviation 9.4105 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Vitality Score: Wk 48 (n=116,102,86) | 7.200 score on a scale | Standard Deviation 10.3652 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Bodily Pain Score: Wk 24 (n=115,106,85) | 11.948 score on a scale | Standard Deviation 10.2846 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Physical Functioning Score: Wk 48 (n=114,102,88) | 8.577 score on a scale | Standard Deviation 10.9439 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Physical Role Score: Wk 48 (n=115,101,87) | 7.873 score on a scale | Standard Deviation 9.6133 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Mental Health Score: Wk 24 (n=115,107,85) | 5.312 score on a scale | Standard Deviation 8.1965 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Emotional Role Score: Wk 24 (n=113,108,85) | 7.180 score on a scale | Standard Deviation 12.0934 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Social Functioning Score: Wk 48 (n=116,102,88) | 7.713 score on a scale | Standard Deviation 11.3046 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Bodily Pain Score: Wk 48 (n=116,101,87) | 12.712 score on a scale | Standard Deviation 10.3962 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Emotional Role Score: Wk 48 (n=114,101,86) | 7.142 score on a scale | Standard Deviation 13.4771 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | General Health Score: Wk 48 (n=115,100,87) | 6.241 score on a scale | Standard Deviation 8.4496 |
| Rituximab High Dose + Methotrexate | Change in SF-36 Score From BL | Vitality Score: Wk 24 (n=115,108,86) | 6.534 score on a scale | Standard Deviation 8.8644 |
Secondary
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR): Adjusted Mean Change From BL at Week 48
DAS28 was calculated according to the following formula: DAS28 equals (=) \[0.56 multiplied by (\*) the square root (√) of TJC\] plus (+) \[0.28 \* √ of SJC\] + (0.70 \* the natural logarithm (ln) ESR in millimeters per hour (mm/h)\] + \[0.014 \* participant's global assessment of disease activity (GH)\]. DAS28-ESR ≥ 5.1 = high disease activity, DAS28-ESR less than or equal to (≤) 3.2 = low disease activity, DAS28-ESR less than (\<) 2.6 = remission.
Time frame: BL, Week 48
Population: ITT-M2 population. Two participants from the Low Dose group and 1 participant from the Escalated Dose group were not evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rituximab Low Dose + Methotrexate | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR): Adjusted Mean Change From BL at Week 48 | -2.13 score on a scale |
| Rituximab Escalated Dose + Methotrexate | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR): Adjusted Mean Change From BL at Week 48 | -2.19 score on a scale |
| Rituximab High Dose + Methotrexate | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR): Adjusted Mean Change From BL at Week 48 | -2.42 score on a scale |
p-value: 0.7127ANOVA
p-value: 0.1018ANOVA
Secondary
Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL)
Cfirst values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2.
Time frame: Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment).
Population: ITT-M2 population, n = number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL) | First Course (n=121,112,91) | 165 µg/mL | Standard Deviation 42 |
| Rituximab Low Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL) | Second Course (n=120,105,84) | 177 µg/mL | Standard Deviation 41 |
| Rituximab Escalated Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL) | First Course (n=121,112,91) | 163 µg/mL | Standard Deviation 39 |
| Rituximab Escalated Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL) | Second Course (n=120,105,84) | 345 µg/mL | Standard Deviation 92 |
| Rituximab High Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL) | First Course (n=121,112,91) | 317 µg/mL | Standard Deviation 94 |
| Rituximab High Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL) | Second Course (n=120,105,84) | 350 µg/mL | Standard Deviation 86 |
Secondary
Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL
Csecond values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2.
Time frame: Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment).
Population: ITT-M2 population, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL | First course (n=130,116,90) | 194 µg/mL | Standard Deviation 65 |
| Rituximab Low Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL | Second course (n=121,107,88) | 209 µg/mL | Standard Deviation 70 |
| Rituximab Escalated Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL | First course (n=130,116,90) | 190 µg/mL | Standard Deviation 57 |
| Rituximab Escalated Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL | Second course (n=121,107,88) | 380 µg/mL | Standard Deviation 139 |
| Rituximab High Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL | First course (n=130,116,90) | 373 µg/mL | Standard Deviation 116 |
| Rituximab High Dose + Methotrexate | Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL | Second course (n=121,107,88) | 392 µg/mL | Standard Deviation 123 |
Secondary
Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative
Percentage of participants who were RF seropositive at BL who became RF seronegative over the course of the study. RF seropositive status was defined as RF ≥ 20 international units (IU) per mL. RF seronegative status was defined as RF \< 20 IU/mL.
Time frame: BL, Weeks 8, 24, and 48
Population: RF seropositive participants from the ITT-M2 population, n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative | Wk 24 (n=83,79,56) | 22.9 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative | Wk 8 (n=93,84,60) | 9.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative | Wk 48 (n=85,78,60) | 30.6 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative | Wk 24 (n=83,79,56) | 21.5 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative | Wk 8 (n=93,84,60) | 9.5 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative | Wk 48 (n=85,78,60) | 30.8 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative | Wk 8 (n=93,84,60) | 5.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative | Wk 48 (n=85,78,60) | 23.3 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative | Wk 24 (n=83,79,56) | 16.1 percentage of participants |
Secondary
Percentage of Participants With a ACR 70% Improvement Criteria (ACR70) Response at Week 48
ACR70 was defined as an overall score of 70 in the ACRn calculation. The Overall score defined as lowest percent improvement from BL of following 3 measures: TJC (68 joints), SJC (66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (VAS), HAQ, and CRP. If CRP missing, ESR was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. LOCF for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR70 set to Non-Responder if ACRn missing.
Time frame: Week 48
Population: ITT-M2 population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a ACR 70% Improvement Criteria (ACR70) Response at Week 48 | 20 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a ACR 70% Improvement Criteria (ACR70) Response at Week 48 | 19 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a ACR 70% Improvement Criteria (ACR70) Response at Week 48 | 23 percentage of participants |
Secondary
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers
ANA titers were obtained by the following serum dilution schema: negative = negative, borderline = 1 diluted to (:) 40 or 1:80, and positive ≥ 1:160. The change categories were defined for the change from BL to Weeks 24 and 48 according to this schema. Negative to borderline was defined as any change from negative to borderline as no dilution is given for negative results. Negative to positive was defined as at least a two-fold positive change in dilution from BL. Borderline to negative was defined as any change from borderline to negative as no dilution is given for negative results. Borderline to positive was defined as at least a two-fold positive change in dilution from BL. Positive to borderline was defined as at least a two-fold negative change in dilution from BL. Positive to negative was defined as at least a two-fold negative change in dilution from BL. Unchanged was defined as any difference in dilution less than two-fold.
Time frame: BL, Weeks 24 and 48
Population: SAP, n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Borderline to Negative (n=112,102,86,4,22) | 23.2 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Positive to Negative (n=112,102,86,4,22) | 4.5 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Negative to Borderline (n=113,107,80,4,24) | 7.1 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Positive to Borderline (n=113,107,80,4,24) | 0.9 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Unchanged (n=113,107,80,4,24) | 77.9 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Unchanged (n=112,102,86,4,22) | 64.3 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Positive to Borderline (n=112,102,86,4,22) | 5.4 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Borderline to Positive (n=113,107,80,4,24) | 0.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Positive to Negative (n=113,107,80,4,24) | 0.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Negative to Borderline (n=112,102,86,4,22) | 2.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Borderline to Negative (n=113,107,80,4,24) | 14.2 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Borderline to Positive (n=112,102,86,4,22) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Unchanged (n=112,102,86,4,22) | 66.7 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Unchanged (n=113,107,80,4,24) | 79.4 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Borderline to Negative (n=113,107,80,4,24) | 16.8 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Negative to Borderline (n=112,102,86,4,22) | 2.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Negative to Borderline (n=113,107,80,4,24) | 1.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Positive to Negative (n=112,102,86,4,22) | 2.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Borderline to Positive (n=113,107,80,4,24) | 0.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Borderline to Negative (n=112,102,86,4,22) | 24.5 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Positive to Borderline (n=112,102,86,4,22) | 3.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Positive to Borderline (n=113,107,80,4,24) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Borderline to Positive (n=112,102,86,4,22) | 1.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Positive to Negative (n=113,107,80,4,24) | 0.9 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Positive to Negative (n=112,102,86,4,22) | 3.5 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Negative to Borderline (n=113,107,80,4,24) | 7.5 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Borderline to Negative (n=113,107,80,4,24) | 11.3 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Borderline to Positive (n=113,107,80,4,24) | 1.3 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Positive to Borderline (n=113,107,80,4,24) | 6.3 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Positive to Negative (n=113,107,80,4,24) | 1.3 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Unchanged (n=113,107,80,4,24) | 72.5 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Negative to Borderline (n=112,102,86,4,22) | 2.3 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Borderline to Negative (n=112,102,86,4,22) | 16.3 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Borderline to Positive (n=112,102,86,4,22) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Positive to Borderline (n=112,102,86,4,22) | 7.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Unchanged (n=112,102,86,4,22) | 70.9 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Unchanged (n=113,107,80,4,24) | 75.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Negative to Borderline (n=113,107,80,4,24) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Borderline to Negative (n=112,102,86,4,22) | 50.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Positive to Negative (n=113,107,80,4,24) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Borderline to Positive (n=112,102,86,4,22) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Positive to Borderline (n=113,107,80,4,24) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Unchanged (n=112,102,86,4,22) | 50.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Positive to Borderline (n=112,102,86,4,22) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Borderline to Positive (n=113,107,80,4,24) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Borderline to Negative (n=113,107,80,4,24) | 25.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Positive to Negative (n=112,102,86,4,22) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Negative to Borderline (n=112,102,86,4,22) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Unchanged (n=113,107,80,4,24) | 95.8 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Positive to Borderline (n=112,102,86,4,22) | 4.5 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Negative to Borderline (n=113,107,80,4,24) | 4.2 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Borderline to Negative (n=112,102,86,4,22) | 9.1 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Borderline to Negative (n=113,107,80,4,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Positive to Borderline (n=113,107,80,4,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Unchanged (n=112,102,86,4,22) | 86.4 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Positive to Negative (n=113,107,80,4,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Borderline to Positive (n=112,102,86,4,22) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Negative to Borderline (n=112,102,86,4,22) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 24, Borderline to Positive (n=113,107,80,4,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers | Wk 48, Positive to Negative (n=112,102,86,4,22) | 0.0 percentage of participants |
Secondary
Percentage of Participants With ACR 50% Improvement Criteria (ACR50) Response at Week 48
ACR50 was defined as an overall score of 50 in the ACRn calculation. Overall score defined as lowest percent improvement from BL of following 3 measures: TJC (68 joints), SJC (66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (VAS), HAQ, and CRP. If CRP missing, ESR was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. LOCF for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR50 set to Non-Responder if ACRn missing.
Time frame: Week 48
Population: ITT-M2 population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants With ACR 50% Improvement Criteria (ACR50) Response at Week 48 | 39 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With ACR 50% Improvement Criteria (ACR50) Response at Week 48 | 39 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With ACR 50% Improvement Criteria (ACR50) Response at Week 48 | 48 percentage of participants |
Secondary
Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category
EULAR responses were categorized according to DAS28-ESR score. DAS28-ESR ≤ 3.2 at Week 48 and a change from BL to Week 48 \< -1.2 = good response, DAS28-ESR ≤ 3.2 or greater than (\>) 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 \< -0.6 and ≥ -1.2 = moderate response, DAS28-ESR \> 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 \< -1.2 = moderate response, DAS28-ESR \> 5.1 at Week 48 and a change from BL to Week 48 \< -1.2 = moderate response, DAS28-ESR ≤ 3.2 or \> 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 ≥ -0.6 = no response, DAS28-ESR \> 5.1 at Week 48 and a change from BL to Week 48 \< -0.6 and ≥ -1.2 or ≥ -0.6 = no response.
Time frame: Week 48
Population: ITT-M2 population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category | Moderate | 50.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category | None | 26.9 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category | Good | 22.4 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category | Moderate | 55.5 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category | None | 27.7 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category | Good | 16.8 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category | None | 10.8 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category | Good | 26.9 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category | Moderate | 62.4 percentage of participants |
p-value: 0.5029Cochran-Mantel-Haenszel
p-value: 0.0495Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN
The LLN for C3 protein was defined as \<0.9 grams per liter (g/L).
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Postdose (n=122,113,82) | 0.8 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Post Retreatment (n=119,107,88) | 5.9 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Pre Retreatment (n=121,105,88) | 6.6 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Week 4 (n=121,113,83) | 3.3 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Predose (n=127,108,86) | 3.1 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Pre Retreatment (n=120,105,86) | 6.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Predose (n=124,115,84) | 2.4 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Postdose (n=122,109,87) | 3.3 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Post Retreatment (n=118,103,82) | 4.2 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Week 4 (n=121,113,83) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Predose (n=127,108,86) | 0.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Postdose (n=122,109,87) | 2.8 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Predose (n=124,115,84) | 0.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Postdose (n=122,113,82) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Pre Retreatment (n=121,105,88) | 1.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Post Retreatment (n=118,103,82) | 2.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Pre Retreatment (n=120,105,86) | 1.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Post Retreatment (n=119,107,88) | 4.7 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Predose (n=124,115,84) | 2.4 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Predose (n=127,108,86) | 1.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Post Retreatment (n=118,103,82) | 7.3 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Postdose (n=122,109,87) | 5.7 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Post Retreatment (n=119,107,88) | 8.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Week 4 (n=121,113,83) | 1.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Postdose (n=122,113,82) | 2.4 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | Day 15 Pre Retreatment (n=120,105,86) | 7.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN | BL Pre Retreatment (n=121,105,88) | 3.4 percentage of participants |
Secondary
Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN
The LLN of C4 protein was defined as \< 0.1 g/L.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Postdose (n=121,113,81) | 2.5 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Post Retreatment (n=119,107,88) | 2.5 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Pre Retreatment (n=121,105,88) | 1.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Wk 4 (n=121,111,81) | 1.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Predose (n=127,108,86) | 2.4 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Pre Retreatment (n=120,105,86) | 1.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Predose (n=124,115,83) | 2.4 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Postdose (n=122,109,87) | 4.9 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Post Retreatment (n=118,103,81) | 1.7 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Wk 4 (n=121,111,81) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Predose (n=127,108,86) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Postdose (n=122,109,87) | 0.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Predose (n=124,115,83) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Postdose (n=121,113,81) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Pre Retreatment (n=121,105,88) | 1.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Post Retreatment (n=118,103,81) | 1.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Pre Retreatment (n=120,105,86) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Post Retreatment (n=119,107,88) | 0.9 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Predose (n=124,115,83) | 2.4 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Predose (n=127,108,86) | 1.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Post Retreatment (n=118,103,81) | 1.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Postdose (n=122,109,87) | 2.3 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Post Retreatment (n=119,107,88) | 1.1 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Wk 4 (n=121,111,81) | 2.5 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Postdose (n=121,113,81) | 1.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | Day 15 Pre Retreatment (n=120,105,86) | 1.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN | BL Pre Retreatment (n=121,105,88) | 1.1 percentage of participants |
Secondary
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN)
Surface expression of CD19 was assessed by FACS analysis as a marker of absolute B lymphocyte count. The LLN was defined as \< 80 cells/µL.
Time frame: BL, Days 1 and 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: ITT-M2 population, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 16 (n=122,112,91,6,23) | 0.8 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 24 (n=114,107,87,4,24) | 7.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 1 Postdose (n=118,109,85,5,23) | 0.8 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 32 (n=122,107,88,5,24) | 2.5 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 4 (n=127,111,87,6,24) | 0.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 40 (n=118,103,84,4,23) | 0.8 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 48 (n=118,105,89,4,22) | 5.9 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 15 Postdose (n=121,108,89,6,23) | 0.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 28 (n=121,103,86,6,25) | 0.8 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 8 (n=126,111,90,6,23) | 0.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 15 Predose (n=127,114,87,5,24) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 8 (n=126,111,90,6,23) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 24 (n=114,107,87,4,24) | 6.5 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 16 (n=122,112,91,6,23) | 0.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 15 Predose (n=127,114,87,5,24) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 1 Postdose (n=118,109,85,5,23) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 40 (n=118,103,84,4,23) | 1.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 15 Postdose (n=121,108,89,6,23) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 48 (n=118,105,89,4,22) | 1.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 32 (n=122,107,88,5,24) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 4 (n=127,111,87,6,24) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 28 (n=121,103,86,6,25) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 16 (n=122,112,91,6,23) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 1 Postdose (n=118,109,85,5,23) | 2.4 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 15 Predose (n=127,114,87,5,24) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 15 Postdose (n=121,108,89,6,23) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 4 (n=127,111,87,6,24) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 8 (n=126,111,90,6,23) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 24 (n=114,107,87,4,24) | 4.6 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 28 (n=121,103,86,6,25) | 2.3 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 32 (n=122,107,88,5,24) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 40 (n=118,103,84,4,23) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 48 (n=118,105,89,4,22) | 5.6 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 4 (n=127,111,87,6,24) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 1 Postdose (n=118,109,85,5,23) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 15 Predose (n=127,114,87,5,24) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 48 (n=118,105,89,4,22) | 50.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 40 (n=118,103,84,4,23) | 50.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 15 Postdose (n=121,108,89,6,23) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 16 (n=122,112,91,6,23) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 28 (n=121,103,86,6,25) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 32 (n=122,107,88,5,24) | 20.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 8 (n=126,111,90,6,23) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 24 (n=114,107,87,4,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 1 Postdose (n=118,109,85,5,23) | 8.7 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 24 (n=114,107,87,4,24) | 12.5 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 4 (n=127,111,87,6,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 28 (n=121,103,86,6,25) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 15 Postdose (n=121,108,89,6,23) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 48 (n=118,105,89,4,22) | 13.6 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 32 (n=122,107,88,5,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Day 15 Predose (n=127,114,87,5,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 40 (n=118,103,84,4,23) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 16 (n=122,112,91,6,23) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) | Wk 8 (n=126,111,90,6,23) | 0.0 percentage of participants |
Secondary
Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers
A participant was defined as being HACA positive if the HACA serum level was ≥ 5 relative units (RU) per mL and the physician comment read that participant was immunodepletable with rituximab.
Time frame: BL, Weeks 24 and 48
Population: SAP, n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | BL (n=131,115,91,6,25) | 0.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | Wk 48 (n=115,104,87,4,22) | 4.3 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | Wk 24 (n=118,109,86,4,24) | 5.1 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | Wk 24 (n=118,109,86,4,24) | 7.3 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | BL (n=131,115,91,6,25) | 0.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | Wk 48 (n=115,104,87,4,22) | 1.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | Wk 24 (n=118,109,86,4,24) | 2.3 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | BL (n=131,115,91,6,25) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | Wk 48 (n=115,104,87,4,22) | 2.3 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | BL (n=131,115,91,6,25) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | Wk 48 (n=115,104,87,4,22) | 25.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | Wk 24 (n=118,109,86,4,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | Wk 24 (n=118,109,86,4,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | BL (n=131,115,91,6,25) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers | Wk 48 (n=115,104,87,4,22) | 0.0 percentage of participants |
Secondary
Percentage of Participants With Positive Recall Antigen Antibody Titers
A positive titer result to recall antigens was defined as a serum antibody level equal to or above the following protective levels: tetanus toxoid ≥ 0.1 IU/mL, influenza A \> 12 U/mL, influenza B \> 12 U/mL, and streptococcus (S.) pneumococcus ≥ 1.0 mg/L.
Time frame: BL, Weeks 24 and 48
Population: SAP, n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Wk 24 (n=118,107,83,4,24) | 72.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Wk 24 (n=114,105,79,4,23) | 94.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Day 1 Predose (n=125,110,88,6,25) | 94.4 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Day 1 Predose (n=130,114,91,6,25) | 100.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Wk 48 (n=116,105,89,4,22) | 100.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Wk 48 (n=114,101,87,4,22) | 94.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Day 1 Predose (n=129,114,88,6,25) | 94.6 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Wk 48 (n=112,100,88,4,21) | 94.6 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Wk 24 (n=118,108,83,4,24) | 100.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Day 1 Predose (n=131,115,91,6,25) | 77.1 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Wk 24 (n=114,107,82,4,24) | 93.9 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Wk 48 (n=118,105,89,4,22) | 71.2 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Wk 48 (n=114,101,87,4,22) | 94.1 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Wk 48 (n=116,105,89,4,22) | 100.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Wk 24 (n=114,107,82,4,24) | 97.2 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Day 1 Predose (n=131,115,91,6,25) | 70.4 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Day 1 Predose (n=125,110,88,6,25) | 98.2 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Wk 24 (n=114,105,79,4,23) | 94.3 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Wk 48 (n=112,100,88,4,21) | 97.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Wk 24 (n=118,107,83,4,24) | 69.2 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Day 1 Predose (n=129,114,88,6,25) | 94.7 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Day 1 Predose (n=130,114,91,6,25) | 100.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Wk 48 (n=118,105,89,4,22) | 66.7 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Wk 24 (n=118,108,83,4,24) | 100.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Wk 24 (n=114,105,79,4,23) | 96.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Day 1 Predose (n=125,110,88,6,25) | 89.8 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Wk 24 (n=114,107,82,4,24) | 90.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Wk 48 (n=112,100,88,4,21) | 89.8 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Day 1 Predose (n=130,114,91,6,25) | 100.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Wk 24 (n=118,108,83,4,24) | 100.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Wk 48 (n=116,105,89,4,22) | 100.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Day 1 Predose (n=131,115,91,6,25) | 75.8 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Wk 24 (n=118,107,83,4,24) | 73.5 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Wk 48 (n=118,105,89,4,22) | 73.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Day 1 Predose (n=129,114,88,6,25) | 97.7 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Wk 48 (n=114,101,87,4,22) | 96.6 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Wk 48 (n=116,105,89,4,22) | 100.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Day 1 Predose (n=125,110,88,6,25) | 100.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Wk 24 (n=118,107,83,4,24) | 75.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Wk 24 (n=118,108,83,4,24) | 100.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Wk 48 (n=118,105,89,4,22) | 75.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Day 1 Predose (n=130,114,91,6,25) | 100.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Wk 48 (n=114,101,87,4,22) | 100.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Day 1 Predose (n=129,114,88,6,25) | 100.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Wk 48 (n=112,100,88,4,21) | 100.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Wk 24 (n=114,107,82,4,24) | 100.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Wk 24 (n=114,105,79,4,23) | 100.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Day 1 Predose (n=131,115,91,6,25) | 66.7 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Wk 48 (n=116,105,89,4,22) | 100.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Day 1 Predose (n=129,114,88,6,25) | 96.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Day 1 Predose (n=125,110,88,6,25) | 92.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Wk 24 (n=118,107,83,4,24) | 62.5 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Wk 24 (n=114,107,82,4,24) | 91.7 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Day 1 Predose (n=130,114,91,6,25) | 100.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Wk 48 (n=114,101,87,4,22) | 100.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | S. Pneumococcus, Wk 24 (n=118,108,83,4,24) | 100.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Wk 48 (n=118,105,89,4,22) | 54.5 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Tetanus Toxoid, Day 1 Predose (n=131,115,91,6,25) | 84.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Rubella, Wk 48 (n=112,100,88,4,21) | 95.2 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Positive Recall Antigen Antibody Titers | Varicella, Wk 24 (n=114,105,79,4,23) | 95.7 percentage of participants |
Secondary
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN
The LLNs for total Ig, IgA, IgG, and IgM were defined as 6.75 grams per liter (g/L), 0.70 g/L, 65 g/L, and 0.40 g/L, respectively.
Time frame: BL, Weeks 24 and 48
Population: ITT-M2 population, n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgM <LLN (n=117,109,83,4,24) | 7.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total Ig <LLN (n=131,113,93,6,25) | 0.8 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgG <LLN (n=117,105,89,4,22) | 1.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgA <LLN (n=131,113,93,6,25) | 0.8 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgM <LLN (n=131,113,93,6,25) | 0.8 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgA <LLN (n=117,109,83,4,24) | 0.0 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgG <LLN (n=117,109,83,4,24) | 0.9 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgA <LLN (n=117,105,89,4,22) | 1.7 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total Ig <LLN (n=117,105,89,4,22) | 0.9 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total Ig <LLN (n=117,109,83,4,24) | 0.9 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgG <LLN (n=131,113,93,6,25) | 2.3 percentage of participants |
| Rituximab Low Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgM <LLN (n=117,105,89,4,22) | 13.7 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgG <LLN (n=131,113,93,6,25) | 0.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgA <LLN (n=117,109,83,4,24) | 0.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgG <LLN (n=117,109,83,4,24) | 0.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgA <LLN (n=131,113,93,6,25) | 0.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total Ig <LLN (n=131,113,93,6,25) | 0.9 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total Ig <LLN (n=117,105,89,4,22) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgG <LLN (n=117,105,89,4,22) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgM <LLN (n=117,109,83,4,24) | 7.3 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgA <LLN (n=117,105,89,4,22) | 1.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgM <LLN (n=131,113,93,6,25) | 0.0 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgM <LLN (n=117,105,89,4,22) | 13.3 percentage of participants |
| Rituximab Escalated Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total Ig <LLN (n=117,109,83,4,24) | 0.9 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgG <LLN (n=117,105,89,4,22) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total Ig <LLN (n=131,113,93,6,25) | 1.1 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgA <LLN (n=131,113,93,6,25) | 2.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgG <LLN (n=131,113,93,6,25) | 2.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgM <LLN (n=131,113,93,6,25) | 1.1 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total Ig <LLN (n=117,109,83,4,24) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgA <LLN (n=117,109,83,4,24) | 1.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgG <LLN (n=117,109,83,4,24) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgM <LLN (n=117,109,83,4,24) | 6.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total Ig <LLN (n=117,105,89,4,22) | 0.0 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgA <LLN (n=117,105,89,4,22) | 2.2 percentage of participants |
| Rituximab High Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgM <LLN (n=117,105,89,4,22) | 10.1 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgA <LLN (n=117,105,89,4,22) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgM <LLN (n=117,109,83,4,24) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgG <LLN (n=131,113,93,6,25) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total Ig <LLN (n=117,105,89,4,22) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgA <LLN (n=131,113,93,6,25) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgG <LLN (n=117,105,89,4,22) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total Ig <LLN (n=117,109,83,4,24) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgM <LLN (n=131,113,93,6,25) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgA <LLN (n=117,109,83,4,24) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total Ig <LLN (n=131,113,93,6,25) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgG <LLN (n=117,109,83,4,24) | 0.0 percentage of participants |
| Rituximab/Placebo + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgM <LLN (n=117,105,89,4,22) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgG <LLN (n=117,109,83,4,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgM <LLN (n=117,109,83,4,24) | 16.7 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgM <LLN (n=131,113,93,6,25) | 4.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgM <LLN (n=117,105,89,4,22) | 18.2 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total Ig <LLN (n=117,105,89,4,22) | 4.5 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgG <LLN (n=131,113,93,6,25) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgA <LLN (n=117,105,89,4,22) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total IgA <LLN (n=131,113,93,6,25) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 48, total IgG <LLN (n=117,105,89,4,22) | 4.5 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total IgA <LLN (n=117,109,83,4,24) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | BL, total Ig <LLN (n=131,113,93,6,25) | 0.0 percentage of participants |
| Rituximab Decreased Dose + Methotrexate | Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN | Wk 24, total Ig <LLN (n=117,109,83,4,24) | 0.0 percentage of participants |
Secondary
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL
Simultaneous surface expression of CD16 and CD56 was assessed by FACS analysis as a marker of NK cell count.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | BL Predose (n=127,110,90) | 172.3 cells/µL | Standard Deviation 102.58 |
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 99.2 cells/µL | Standard Deviation 51.46 |
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 175.7 cells/µL | Standard Deviation 95.76 |
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 170.8 cells/µL | Standard Deviation 100.96 |
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 180.1 cells/µL | Standard Deviation 103.51 |
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 197.7 cells/µL | Standard Deviation 107.89 |
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 201.7 cells/µL | Standard Deviation 115.66 |
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 188.8 cells/µL | Standard Deviation 93.43 |
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 203.4 cells/µL | Standard Deviation 120.7 |
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 212.5 cells/µL | Standard Deviation 127.77 |
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 222.4 cells/µL | Standard Deviation 145.8 |
| Rituximab Low Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 208.4 cells/µL | Standard Deviation 117.23 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 216.2 cells/µL | Standard Deviation 128.45 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | BL Predose (n=127,110,90) | 173.5 cells/µL | Standard Deviation 100.55 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 193.8 cells/µL | Standard Deviation 120.85 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 200.1 cells/µL | Standard Deviation 119.07 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 111.7 cells/µL | Standard Deviation 56.35 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 189.3 cells/µL | Standard Deviation 105.93 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 213.0 cells/µL | Standard Deviation 127.08 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 180.6 cells/µL | Standard Deviation 114.27 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 201.8 cells/µL | Standard Deviation 120.24 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 182.0 cells/µL | Standard Deviation 110.95 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 181.8 cells/µL | Standard Deviation 103.36 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 219.0 cells/µL | Standard Deviation 130.92 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 173.7 cells/µL | Standard Deviation 96.23 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 173.2 cells/µL | Standard Deviation 94.15 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 193.8 cells/µL | Standard Deviation 93.87 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 177.8 cells/µL | Standard Deviation 92.23 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 184.1 cells/µL | Standard Deviation 87.33 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 182.6 cells/µL | Standard Deviation 99.76 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 214.8 cells/µL | Standard Deviation 122.52 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | BL Predose (n=127,110,90) | 174.3 cells/µL | Standard Deviation 99.82 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 92.4 cells/µL | Standard Deviation 52.96 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 200.8 cells/µL | Standard Deviation 114.49 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 168.8 cells/µL | Standard Deviation 84.38 |
| Rituximab High Dose + Methotrexate | Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 212.2 cells/µL | Standard Deviation 111.62 |
Secondary
Peripheral CD19+CD27+ B Cell Count in Cells/µL
Simultaneous surface expression of CD19 and CD27 was assessed by FACS analysis as a marker of memory B lymphocyte count.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | BL Predose (n=113,98,75) | 41.4 cells/µL | Standard Deviation 41.79 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | BL Postdose (n=105,94,72) | 4.6 cells/µL | Standard Deviation 2.85 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Day 15 Predose (n=112,99,75) | 5.1 cells/µL | Standard Deviation 4.65 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Day 15 Postdose (n=103,89,70) | 3.0 cells/µL | Standard Deviation 0.2 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 4 (n=110,92,74) | 4.6 cells/µL | Standard Deviation 3.56 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 8 (n=110,92,75) | 4.6 cells/µL | Standard Deviation 2.98 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 16 (n=104,93,75) | 5.5 cells/µL | Standard Deviation 4.2 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 24 (n=97,91,67) | 6.8 cells/µL | Standard Deviation 4.67 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 28 (n=101,86,72) | 5.3 cells/µL | Standard Deviation 3.97 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 32 (n=105,88,73) | 5.7 cells/µL | Standard Deviation 5.35 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 40 (n=99,84,67) | 5.6 cells/µL | Standard Deviation 6.24 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 48 (n=96,87,70) | 5.4 cells/µL | Standard Deviation 4.04 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 48 (n=96,87,70) | 5.3 cells/µL | Standard Deviation 4.11 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | BL Predose (n=113,98,75) | 42.2 cells/µL | Standard Deviation 40.74 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 16 (n=104,93,75) | 5.5 cells/µL | Standard Deviation 4.39 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 28 (n=101,86,72) | 4.8 cells/µL | Standard Deviation 3.54 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | BL Postdose (n=105,94,72) | 5.1 cells/µL | Standard Deviation 4.2 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 8 (n=110,92,75) | 4.3 cells/µL | Standard Deviation 2.51 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 40 (n=99,84,67) | 4.7 cells/µL | Standard Deviation 3.41 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Day 15 Predose (n=112,99,75) | 4.5 cells/µL | Standard Deviation 3.4 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 24 (n=97,91,67) | 6.8 cells/µL | Standard Deviation 5.95 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 4 (n=110,92,74) | 4.0 cells/µL | Standard Deviation 2.7 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Day 15 Postdose (n=103,89,70) | 3.0 cells/µL | Standard Deviation 0.24 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 32 (n=105,88,73) | 4.5 cells/µL | Standard Deviation 3.38 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Day 15 Postdose (n=103,89,70) | 3.0 cells/µL | Standard Deviation 0.27 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 4 (n=110,92,74) | 4.6 cells/µL | Standard Deviation 4.57 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 32 (n=105,88,73) | 5.3 cells/µL | Standard Deviation 4.14 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 8 (n=110,92,75) | 4.6 cells/µL | Standard Deviation 2.73 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 16 (n=104,93,75) | 4.9 cells/µL | Standard Deviation 4.33 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 24 (n=97,91,67) | 7.1 cells/µL | Standard Deviation 5.8 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 40 (n=99,84,67) | 4.9 cells/µL | Standard Deviation 4.28 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | BL Predose (n=113,98,75) | 42.3 cells/µL | Standard Deviation 33.71 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | BL Postdose (n=105,94,72) | 4.7 cells/µL | Standard Deviation 3.4 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 28 (n=101,86,72) | 4.1 cells/µL | Standard Deviation 2.51 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Day 15 Predose (n=112,99,75) | 4.5 cells/µL | Standard Deviation 2.83 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27+ B Cell Count in Cells/µL | Wk 48 (n=96,87,70) | 6.5 cells/µL | Standard Deviation 11.94 |
Secondary
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL
Surface expression of CD19 in the absence of CD27 expression was assessed by FACS analysis as a marker of naive B lymphocyte count.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | BL Predose (n=113,98,75) | 141.1 cells/µL | Standard Deviation 108.9 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | BL Postdose (n=105,94,72) | 16.7 cells/µL | Standard Deviation 13.1 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Day 15 Predose (n=112,99,75) | 10.2 cells/µL | Standard Deviation 1.39 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Day 15 Postdose (n=103,89,70) | 10.0 cells/µL | Standard Deviation 0 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 4 (n=110,92,74) | 10.1 cells/µL | Standard Deviation 0.9 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 8 (n=110,92,75) | 10.1 cells/µL | Standard Deviation 0.49 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 16 (n=104,93,75) | 11.3 cells/µL | Standard Deviation 6.65 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 24 (n=97,91,67) | 23.3 cells/µL | Standard Deviation 25.11 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 28 (n=101,86,72) | 11.0 cells/µL | Standard Deviation 9.15 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 32 (n=105,88,73) | 13.8 cells/µL | Standard Deviation 27.58 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 40 (n=99,84,67) | 10.7 cells/µL | Standard Deviation 4.33 |
| Rituximab Low Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 48 (n=96,87,70) | 18.8 cells/µL | Standard Deviation 22.13 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 48 (n=96,87,70) | 13.0 cells/µL | Standard Deviation 11.67 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | BL Predose (n=113,98,75) | 126.4 cells/µL | Standard Deviation 75 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 16 (n=104,93,75) | 11.7 cells/µL | Standard Deviation 6.55 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 28 (n=101,86,72) | 10.5 cells/µL | Standard Deviation 3.3 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | BL Postdose (n=105,94,72) | 15.2 cells/µL | Standard Deviation 9.5 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 8 (n=110,92,75) | 10.1 cells/µL | Standard Deviation 0.44 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 40 (n=99,84,67) | 11.3 cells/µL | Standard Deviation 8.7 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Day 15 Predose (n=112,99,75) | 10.2 cells/µL | Standard Deviation 0.94 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 24 (n=97,91,67) | 21.7 cells/µL | Standard Deviation 23.5 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 4 (n=110,92,74) | 10.1 cells/µL | Standard Deviation 0.56 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Day 15 Postdose (n=103,89,70) | 10.0 cells/µL | Standard Deviation 0 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 32 (n=105,88,73) | 10.9 cells/µL | Standard Deviation 4.07 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Day 15 Postdose (n=103,89,70) | 10.0 cells/µL | Standard Deviation 0 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 4 (n=110,92,74) | 10.4 cells/µL | Standard Deviation 1.68 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 32 (n=105,88,73) | 10.7 cells/µL | Standard Deviation 5.86 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 8 (n=110,92,75) | 10.4 cells/µL | Standard Deviation 1.77 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 16 (n=104,93,75) | 10.5 cells/µL | Standard Deviation 2.04 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 24 (n=97,91,67) | 20.8 cells/µL | Standard Deviation 20.89 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 40 (n=99,84,67) | 11.0 cells/µL | Standard Deviation 7.59 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | BL Predose (n=113,98,75) | 179.3 cells/µL | Standard Deviation 169.38 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | BL Postdose (n=105,94,72) | 19.3 cells/µL | Standard Deviation 21.92 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 28 (n=101,86,72) | 13.7 cells/µL | Standard Deviation 19.34 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Day 15 Predose (n=112,99,75) | 10.2 cells/µL | Standard Deviation 1.07 |
| Rituximab High Dose + Methotrexate | Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL | Wk 48 (n=96,87,70) | 15.8 cells/µL | Standard Deviation 18.69 |
Secondary
Peripheral CD20+ B Cell Count in Cells/µL
Surface expression of CD20 was assessed by FACS analysis as a marker of mature and memory B lymphocyte count.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: The safety analysis population (SAP) = ITT-M2 population, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | BL Predose (n=113,97,75) | 184.8 cells/µL | Standard Deviation 135.29 |
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | BL Postdose (n=105,94,71) | 0.2 cells/µL | Standard Deviation 0.58 |
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Day 15 Predose (n=112,101,75) | 0.6 cells/µL | Standard Deviation 1.76 |
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Day 15 Postdose (n=104,91,70) | 1.0 cells/µL | Standard Deviation 7.35 |
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 4 (n=110,95,72) | 0.6 cells/µL | Standard Deviation 3.21 |
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 8 (n=111,92,73) | 0.3 cells/µL | Standard Deviation 0.64 |
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 16 (n=105,93,75) | 2.4 cells/µL | Standard Deviation 8.02 |
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 24 (n=99,92,67) | 20.2 cells/µL | Standard Deviation 53.56 |
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 28 (n=101,85,72) | 1.5 cells/µL | Standard Deviation 12.14 |
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 32 (n=107,88,74) | 5.1 cells/µL | Standard Deviation 33.42 |
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 40 (n=100,86,68) | 1.4 cells/µL | Standard Deviation 5.44 |
| Rituximab Low Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 48 (n=100,89,73) | 12.4 cells/µL | Standard Deviation 26.89 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 48 (n=100,89,73) | 4.4 cells/µL | Standard Deviation 10.7 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | BL Predose (n=113,97,75) | 173.4 cells/µL | Standard Deviation 99.18 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 16 (n=105,93,75) | 3.0 cells/µL | Standard Deviation 8.67 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 28 (n=101,85,72) | 1.1 cells/µL | Standard Deviation 5.82 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | BL Postdose (n=105,94,71) | 0.2 cells/µL | Standard Deviation 0.49 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 8 (n=111,92,73) | 4.9 cells/µL | Standard Deviation 42.09 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 40 (n=100,86,68) | 1.7 cells/µL | Standard Deviation 7.94 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Day 15 Predose (n=112,101,75) | 0.4 cells/µL | Standard Deviation 0.74 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 24 (n=99,92,67) | 15.2 cells/µL | Standard Deviation 25.98 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 4 (n=110,95,72) | 0.2 cells/µL | Standard Deviation 0.5 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Day 15 Postdose (n=104,91,70) | 0.2 cells/µL | Standard Deviation 0.63 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 32 (n=107,88,74) | 1.1 cells/µL | Standard Deviation 4.93 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Day 15 Postdose (n=104,91,70) | 0.1 cells/µL | Standard Deviation 0.39 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 4 (n=110,95,72) | 0.3 cells/µL | Standard Deviation 0.74 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 32 (n=107,88,74) | 1.1 cells/µL | Standard Deviation 6.88 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 8 (n=111,92,73) | 0.3 cells/µL | Standard Deviation 0.86 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 16 (n=105,93,75) | 0.9 cells/µL | Standard Deviation 3.15 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 24 (n=99,92,67) | 13.2 cells/µL | Standard Deviation 23.96 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 40 (n=100,86,68) | 1.6 cells/µL | Standard Deviation 9.11 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | BL Predose (n=113,97,75) | 218.1 cells/µL | Standard Deviation 158.16 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | BL Postdose (n=105,94,71) | 0.2 cells/µL | Standard Deviation 0.65 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 28 (n=101,85,72) | 4.5 cells/µL | Standard Deviation 20.59 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Day 15 Predose (n=112,101,75) | 0.3 cells/µL | Standard Deviation 0.57 |
| Rituximab High Dose + Methotrexate | Peripheral CD20+ B Cell Count in Cells/µL | Wk 48 (n=100,89,73) | 8.2 cells/µL | Standard Deviation 22.12 |
Secondary
Peripheral CD22+ B Cell Count in Cells/µL
Surface expression of CD22 was assessed by FACS analysis as a marker of mature lymphocyte count.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | BL Predose (n=113,97,75) | 188.0 cells/µL | Standard Deviation 135.54 |
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | BL Postdose (n=105,94,71) | 24.5 cells/µL | Standard Deviation 20.59 |
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Day 15 Predose (n=112,101,75) | 5.0 cells/µL | Standard Deviation 6.33 |
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Day 15 Postdose (n=104,91,70) | 1.9 cells/µL | Standard Deviation 1.92 |
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 4 (n=110,95,72) | 4.1 cells/µL | Standard Deviation 5.61 |
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 8 (n=111,92,73) | 3.6 cells/µL | Standard Deviation 5.14 |
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 16 (n=105,93,75) | 5.1 cells/µL | Standard Deviation 8.6 |
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 24 (n=99,92,67) | 20.1 cells/µL | Standard Deviation 32.29 |
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 28 (n=101,85,72) | 4.2 cells/µL | Standard Deviation 13.16 |
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 32 (n=107,88,74) | 8.0 cells/µL | Standard Deviation 33.71 |
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 40 (n=100,86,68) | 3.7 cells/µL | Standard Deviation 6.92 |
| Rituximab Low Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 48 (n=100,89,73) | 14.3 cells/µL | Standard Deviation 26.88 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 48 (n=100,89,73) | 6.3 cells/µL | Standard Deviation 10.77 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | BL Predose (n=113,97,75) | 177.1 cells/µL | Standard Deviation 98.69 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 16 (n=105,93,75) | 6.1 cells/µL | Standard Deviation 9.83 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 28 (n=101,85,72) | 4.0 cells/µL | Standard Deviation 8.07 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | BL Postdose (n=105,94,71) | 23.2 cells/µL | Standard Deviation 17.39 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 8 (n=111,92,73) | 8.4 cells/µL | Standard Deviation 41.87 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 40 (n=100,86,68) | 3.5 cells/µL | Standard Deviation 8.05 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Day 15 Predose (n=112,101,75) | 5.0 cells/µL | Standard Deviation 6.03 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 24 (n=99,92,67) | 17.6 cells/µL | Standard Deviation 25.81 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 4 (n=110,95,72) | 3.8 cells/µL | Standard Deviation 5.44 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Day 15 Postdose (n=104,91,70) | 1.9 cells/µL | Standard Deviation 1.77 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 32 (n=107,88,74) | 3.7 cells/µL | Standard Deviation 8.58 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Day 15 Postdose (n=104,91,70) | 2.4 cells/µL | Standard Deviation 3.23 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 4 (n=110,95,72) | 4.0 cells/µL | Standard Deviation 7.73 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 32 (n=107,88,74) | 3.6 cells/µL | Standard Deviation 8.51 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 8 (n=111,92,73) | 3.9 cells/µL | Standard Deviation 6.03 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 16 (n=105,93,75) | 3.6 cells/µL | Standard Deviation 5.94 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 24 (n=99,92,67) | 16.6 cells/µL | Standard Deviation 25.7 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 40 (n=100,86,68) | 4.0 cells/µL | Standard Deviation 10.01 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | BL Predose (n=113,97,75) | 221.6 cells/µL | Standard Deviation 158.82 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | BL Postdose (n=105,94,71) | 29.0 cells/µL | Standard Deviation 31.51 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 28 (n=101,85,72) | 8.2 cells/µL | Standard Deviation 21.96 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Day 15 Predose (n=112,101,75) | 5.1 cells/µL | Standard Deviation 6.3 |
| Rituximab High Dose + Methotrexate | Peripheral CD22+ B Cell Count in Cells/µL | Wk 48 (n=100,89,73) | 9.8 cells/µL | Standard Deviation 22.24 |
Secondary
Peripheral CD3+ T Cell Count in Cells/µL
Surface expression of CD3 was assessed by FACS analysis as a marker of absolute T lymphocyte count. The normal range of CD3+ T cells was defined as 723-2737 cells/µL.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 237.8 cells/µL | Standard Deviation 133.09 |
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 1231.0 cells/µL | Standard Deviation 585.6 |
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 302.5 cells/µL | Standard Deviation 149.8 |
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 1283.9 cells/µL | Standard Deviation 620.88 |
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 1262.8 cells/µL | Standard Deviation 643.6 |
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | BL Predose (n=127,110,90) | 1262.1 cells/µL | Standard Deviation 651.88 |
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 1318.8 cells/µL | Standard Deviation 650.01 |
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 1256.0 cells/µL | Standard Deviation 580.95 |
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 1280.6 cells/µL | Standard Deviation 622.21 |
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 1282.4 cells/µL | Standard Deviation 587.75 |
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 1332.1 cells/µL | Standard Deviation 658.82 |
| Rituximab Low Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 1300.3 cells/µL | Standard Deviation 670.68 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 1297.1 cells/µL | Standard Deviation 602.07 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 1223.6 cells/µL | Standard Deviation 505.72 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 1286.0 cells/µL | Standard Deviation 522.82 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 1293.9 cells/µL | Standard Deviation 559.38 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 350.0 cells/µL | Standard Deviation 220.23 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 1251.8 cells/µL | Standard Deviation 511.15 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 1193.6 cells/µL | Standard Deviation 505.68 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 263.4 cells/µL | Standard Deviation 167.58 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 1317.3 cells/µL | Standard Deviation 629.87 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | BL Predose (n=127,110,90) | 1229.6 cells/µL | Standard Deviation 565.79 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 1317.1 cells/µL | Standard Deviation 605.57 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 1292.5 cells/µL | Standard Deviation 589.57 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 1315.8 cells/µL | Standard Deviation 598.66 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | BL Predose (n=127,110,90) | 1319.7 cells/µL | Standard Deviation 569.57 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 226.9 cells/µL | Standard Deviation 122.02 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 1356.0 cells/µL | Standard Deviation 604.98 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 343.3 cells/µL | Standard Deviation 184.44 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 1264.8 cells/µL | Standard Deviation 508.87 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 1296.0 cells/µL | Standard Deviation 534.19 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 1260.2 cells/µL | Standard Deviation 562.16 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 1314.9 cells/µL | Standard Deviation 511.18 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 1327.7 cells/µL | Standard Deviation 590.38 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 1312.6 cells/µL | Standard Deviation 509.52 |
| Rituximab High Dose + Methotrexate | Peripheral CD3+ T Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 1306.4 cells/µL | Standard Deviation 508.49 |
Secondary
Peripheral CD4+ T Cell Count in Cells/µL
Surface expression of CD4 was assessed by FACS analysis as a marker of T helper cell count. The normal range of CD4+ T cells was defined as 404-1612 cells/µL.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | BL Predose (n=127,110,90) | 900.4 cells/µL | Standard Deviation 500.42 |
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 130.2 cells/µL | Standard Deviation 81.65 |
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 920.2 cells/µL | Standard Deviation 468.01 |
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 165.4 cells/µL | Standard Deviation 92.96 |
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 880.5 cells/µL | Standard Deviation 456.63 |
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 903.3 cells/µL | Standard Deviation 514.94 |
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 889.2 cells/µL | Standard Deviation 436.84 |
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 969.6 cells/µL | Standard Deviation 553.17 |
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 936.6 cells/µL | Standard Deviation 539.94 |
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 939.0 cells/µL | Standard Deviation 515.71 |
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 908.7 cells/µL | Standard Deviation 478.4 |
| Rituximab Low Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 908.2 cells/µL | Standard Deviation 477.46 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 889.8 cells/µL | Standard Deviation 378.08 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | BL Predose (n=127,110,90) | 876.7 cells/µL | Standard Deviation 398.85 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 937.8 cells/µL | Standard Deviation 450.52 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 870.2 cells/µL | Standard Deviation 373.17 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 145.9 cells/µL | Standard Deviation 86.22 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 949.2 cells/µL | Standard Deviation 462.71 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 901.9 cells/µL | Standard Deviation 383.73 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 930.1 cells/µL | Standard Deviation 424.72 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 918.4 cells/µL | Standard Deviation 434.08 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 859.7 cells/µL | Standard Deviation 373.69 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 196.7 cells/µL | Standard Deviation 124.38 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 911.6 cells/µL | Standard Deviation 404.4 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 196.9 cells/µL | Standard Deviation 132.65 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 917.9 cells/µL | Standard Deviation 431.93 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 950.9 cells/µL | Standard Deviation 439.04 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 950.5 cells/µL | Standard Deviation 458.27 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 910.1 cells/µL | Standard Deviation 472.95 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 948.2 cells/µL | Standard Deviation 418.09 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 942.6 cells/µL | Standard Deviation 422.23 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | BL Predose (n=127,110,90) | 953.6 cells/µL | Standard Deviation 462.18 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 129.8 cells/µL | Standard Deviation 75.17 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 967.0 cells/µL | Standard Deviation 496.62 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 991.9 cells/µL | Standard Deviation 504.25 |
| Rituximab High Dose + Methotrexate | Peripheral CD4+ T Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 952.7 cells/µL | Standard Deviation 487.98 |
Secondary
Peripheral CD8+ T Cell Count in Cells/µL
Surface expression of CD8 was assessed by FACS analysis as a marker of cytotoxic T lymphocyte count. The normal range of CD8+ T cells was defined as 220-1129 cells/µL.
Time frame: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48
Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | BL Predose (n=127,110,90) | 361.8 cells/µL | Standard Deviation 231.86 |
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 106.8 cells/µL | Standard Deviation 70.64 |
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 358.8 cells/µL | Standard Deviation 196.37 |
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 134.0 cells/µL | Standard Deviation 79.79 |
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 348.4 cells/µL | Standard Deviation 202.67 |
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 357.3 cells/µL | Standard Deviation 199.77 |
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 365.1 cells/µL | Standard Deviation 220.35 |
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 359.1 cells/µL | Standard Deviation 189.24 |
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 359.9 cells/µL | Standard Deviation 208.91 |
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 372.3 cells/µL | Standard Deviation 213.84 |
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 367.8 cells/µL | Standard Deviation 215.21 |
| Rituximab Low Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 365.9 cells/µL | Standard Deviation 218.78 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 357.8 cells/µL | Standard Deviation 210.51 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | BL Predose (n=127,110,90) | 352.6 cells/µL | Standard Deviation 228.43 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 377.8 cells/µL | Standard Deviation 227.32 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 353.7 cells/µL | Standard Deviation 221.13 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 118.6 cells/µL | Standard Deviation 104.11 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 367.9 cells/µL | Standard Deviation 239.39 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 386.7 cells/µL | Standard Deviation 260.49 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 360.9 cells/µL | Standard Deviation 232.26 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 382.0 cells/µL | Standard Deviation 241.73 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 330.7 cells/µL | Standard Deviation 197.94 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 152.6 cells/µL | Standard Deviation 130.11 |
| Rituximab Escalated Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 372.7 cells/µL | Standard Deviation 211.86 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Day 15 Postdose (n=121,108,89) | 145.6 cells/µL | Standard Deviation 95.64 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 4 (n=127,111,87) | 341.9 cells/µL | Standard Deviation 164.61 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 32 (n=122,107,88) | 359.9 cells/µL | Standard Deviation 169.32 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 8 (n=126,111,90) | 342.3 cells/µL | Standard Deviation 159.31 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 16 (n=122,112,91) | 344.2 cells/µL | Standard Deviation 169.67 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 24 (n=113,107,85) | 363.3 cells/µL | Standard Deviation 184.04 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 40 (n=118,103,84) | 356.7 cells/µL | Standard Deviation 166.19 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | BL Predose (n=127,110,90) | 364.9 cells/µL | Standard Deviation 181.22 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | BL Postdose (n=118,109,85) | 98.1 cells/µL | Standard Deviation 70.68 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 28 (n=120,101,86) | 357.3 cells/µL | Standard Deviation 182.9 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Day 15 Predose (n=127,114,87) | 359.7 cells/µL | Standard Deviation 174.12 |
| Rituximab High Dose + Methotrexate | Peripheral CD8+ T Cell Count in Cells/µL | Wk 48 (n=114,103,83) | 355.5 cells/µL | Standard Deviation 178.67 |
Secondary
Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL)
Surface expression of CD19 was assessed by fluorescence-activated cell sorting (FACS) analysis as a marker of absolute B lymphocyte count.
Time frame: BL
Population: ITT-M2 population. 7, 8, 3, 1, and 2 participants were not analyzed for this outcome measure from the Low Dose, Escalated Dose, High Dose, Placebo, and Decreased Dose groups, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL) | 183.6 cells/µL | Standard Deviation 142.31 |
| Rituximab Escalated Dose + Methotrexate | Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL) | 168.9 cells/µL | Standard Deviation 94.98 |
| Rituximab High Dose + Methotrexate | Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL) | 205.3 cells/µL | Standard Deviation 171.91 |
| Rituximab/Placebo + Methotrexate | Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL) | 318.2 cells/µL | Standard Deviation 174.62 |
| Rituximab Decreased Dose + Methotrexate | Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL) | 235.4 cells/µL | Standard Deviation 112.56 |
Secondary
Short-Form 36 Health Survey (SF-36) Score
SF-36 scores were obtained by scoring participants' responses to a 36 item questionnaire. SF-36 evaluated 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health from a range of 1 (better) to 5 (worst). The score for each section was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). These 8 aspects were summarized as physical and mental component scores.
Time frame: BL, Week (Wk) 24 and 48
Population: ITT-M2 population, n (number) = number of participants analyzed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Social Functioning Score: Wk 24 (n=118,109,87) | 40.765 score on a scale | Standard Deviation 10.5247 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Mental Health Score: Wk 24 (n=118,108,87) | 43.506 score on a scale | Standard Deviation 11.5661 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Role Score: BL (n=127,116,90) | 31.013 score on a scale | Standard Deviation 9.5785 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Vitality Score: Wk 48 (n=119,103,87) | 46.905 score on a scale | Standard Deviation 10.5538 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Mental Health Score: Wk 48 (n=119,102,88) | 44.529 score on a scale | Standard Deviation 11.7796 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Bodily Pain Score: Wk 24 (n=118,108,87) | 39.709 score on a scale | Standard Deviation 9.2218 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Bodily Pain Score: Wk 48 (n=119,103,89) | 41.318 score on a scale | Standard Deviation 9.2879 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Functioning Score: BL (n=127,116,91) | 28.826 score on a scale | Standard Deviation 9.5523 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Social Functioning Score: Wk 48 (n=119,103,89) | 42.366 score on a scale | Standard Deviation 11.1916 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | General Health Score: Wk 48 (n=118,101,89) | 41.138 score on a scale | Standard Deviation 10.3191 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Functioning Score: Wk 24 (n=116,109,86) | 34.286 score on a scale | Standard Deviation 11.1702 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Mental Health Score: BL (n=128,116,90) | 38.443 score on a scale | Standard Deviation 12.4207 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Bodily Pain Score: BL (n=128,115,90) | 31.657 score on a scale | Standard Deviation 7.5764 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Functioning Score: Wk 48 (n=118,103,89) | 35.291 score on a scale | Standard Deviation 11.7203 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Vitality Score: BL (n=128,116,91) | 38.253 score on a scale | Standard Deviation 10.2709 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | General Health Score: BL (n=127,116,90) | 34.850 score on a scale | Standard Deviation 9.5814 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Emotional Role Score: BL (n=127,115,90) | 33.719 score on a scale | Standard Deviation 13.9238 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Social Functioning Score: BL (n=128,116,91) | 34.948 score on a scale | Standard Deviation 11.6147 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Role Score: Wk 24 (n=117,109,86) | 37.694 score on a scale | Standard Deviation 9.8439 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Emotional Role Score: Wk 24 (n=117,109,87) | 39.665 score on a scale | Standard Deviation 13.1752 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Vitality Score: Wk 24 (n=118,109,87) | 45.000 score on a scale | Standard Deviation 10.7039 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Role Score: Wk 48 (n=119,102,89) | 38.599 score on a scale | Standard Deviation 10.9559 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Emotional Role Score: Wk 48 (n=118,102,88) | 40.429 score on a scale | Standard Deviation 13.7266 |
| Rituximab Low Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | General Health Score: Wk 24 (n=116,109,87) | 39.644 score on a scale | Standard Deviation 9.8338 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Emotional Role Score: Wk 48 (n=118,102,88) | 39.644 score on a scale | Standard Deviation 12.7514 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Role Score: BL (n=127,116,90) | 30.864 score on a scale | Standard Deviation 8.7546 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | General Health Score: Wk 24 (n=116,109,87) | 39.805 score on a scale | Standard Deviation 10.2346 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Role Score: Wk 24 (n=117,109,86) | 36.977 score on a scale | Standard Deviation 9.6325 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Vitality Score: Wk 48 (n=119,103,87) | 46.251 score on a scale | Standard Deviation 10.8299 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Role Score: Wk 48 (n=119,102,89) | 39.086 score on a scale | Standard Deviation 9.623 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Social Functioning Score: BL (n=128,116,91) | 33.341 score on a scale | Standard Deviation 11.3817 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | General Health Score: Wk 48 (n=118,101,89) | 41.555 score on a scale | Standard Deviation 9.9892 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Social Functioning Score: Wk 24 (n=118,109,87) | 40.737 score on a scale | Standard Deviation 10.4537 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Social Functioning Score: Wk 48 (n=119,103,89) | 42.235 score on a scale | Standard Deviation 11.0464 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Vitality Score: BL (n=128,116,91) | 38.096 score on a scale | Standard Deviation 9.5184 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Mental Health Score: BL (n=128,116,90) | 38.307 score on a scale | Standard Deviation 11.9908 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Vitality Score: Wk 24 (n=118,109,87) | 44.577 score on a scale | Standard Deviation 11.1008 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Bodily Pain Score: Wk 24 (n=118,108,87) | 38.875 score on a scale | Standard Deviation 8.3432 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Mental Health Score: Wk 24 (n=118,108,87) | 43.209 score on a scale | Standard Deviation 10.7315 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Mental Health Score: Wk 48 (n=119,102,88) | 44.447 score on a scale | Standard Deviation 11.9128 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Functioning Score: BL (n=127,116,91) | 28.223 score on a scale | Standard Deviation 9.873 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Bodily Pain Score: Wk 48 (n=119,103,89) | 40.836 score on a scale | Standard Deviation 8.6176 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Functioning Score: Wk 24 (n=116,109,86) | 33.929 score on a scale | Standard Deviation 11.3543 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Functioning Score: Wk 48 (n=118,103,89) | 35.318 score on a scale | Standard Deviation 10.668 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Emotional Role Score: BL (n=127,115,90) | 32.217 score on a scale | Standard Deviation 11.9819 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | General Health Score: BL (n=127,116,90) | 34.692 score on a scale | Standard Deviation 9.3289 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Emotional Role Score: Wk 24 (n=117,109,87) | 37.406 score on a scale | Standard Deviation 13.279 |
| Rituximab Escalated Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Bodily Pain Score: BL (n=128,115,90) | 30.815 score on a scale | Standard Deviation 6.5633 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Emotional Role Score: Wk 24 (n=117,109,87) | 39.928 score on a scale | Standard Deviation 13.4008 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Vitality Score: Wk 48 (n=119,103,87) | 47.462 score on a scale | Standard Deviation 11.3098 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Bodily Pain Score: BL (n=128,115,90) | 30.319 score on a scale | Standard Deviation 6.2328 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Bodily Pain Score: Wk 24 (n=118,108,87) | 42.736 score on a scale | Standard Deviation 9.7885 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Bodily Pain Score: Wk 48 (n=119,103,89) | 43.105 score on a scale | Standard Deviation 9.4713 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | General Health Score: BL (n=127,116,90) | 34.025 score on a scale | Standard Deviation 8.8533 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | General Health Score: Wk 24 (n=116,109,87) | 39.050 score on a scale | Standard Deviation 10.4236 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | General Health Score: Wk 48 (n=118,101,89) | 40.427 score on a scale | Standard Deviation 10.5756 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Mental Health Score: BL (n=128,116,90) | 38.405 score on a scale | Standard Deviation 11.1899 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Mental Health Score: Wk 24 (n=118,108,87) | 43.955 score on a scale | Standard Deviation 10.6107 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Mental Health Score: Wk 48 (n=119,102,88) | 43.640 score on a scale | Standard Deviation 11.5868 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Functioning Score: BL (n=127,116,91) | 29.896 score on a scale | Standard Deviation 8.7899 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Functioning Score: Wk 24 (n=116,109,86) | 37.323 score on a scale | Standard Deviation 10.5428 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Functioning Score: Wk 48 (n=118,103,89) | 38.547 score on a scale | Standard Deviation 11.6649 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Emotional Role Score: BL (n=127,115,90) | 32.167 score on a scale | Standard Deviation 13.6914 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Vitality Score: Wk 24 (n=118,109,87) | 46.206 score on a scale | Standard Deviation 10.0519 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Emotional Role Score: Wk 48 (n=118,102,88) | 39.800 score on a scale | Standard Deviation 14.0611 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Role Score: BL (n=127,116,90) | 32.309 score on a scale | Standard Deviation 9.4529 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Role Score: Wk 24 (n=117,109,86) | 39.027 score on a scale | Standard Deviation 10.905 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Physical Role Score: Wk 48 (n=119,102,89) | 40.362 score on a scale | Standard Deviation 10.1419 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Social Functioning Score: BL (n=128,116,91) | 35.812 score on a scale | Standard Deviation 12.2109 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Social Functioning Score: Wk 24 (n=118,109,87) | 42.869 score on a scale | Standard Deviation 10.8028 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Social Functioning Score: Wk 48 (n=119,103,89) | 43.613 score on a scale | Standard Deviation 11.3599 |
| Rituximab High Dose + Methotrexate | Short-Form 36 Health Survey (SF-36) Score | Vitality Score: BL (n=128,116,91) | 39.832 score on a scale | Standard Deviation 10.2209 |
Secondary
Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days
t1/2 values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2.
Time frame: Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment).
Population: ITT-M2 population, n = number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Low Dose + Methotrexate | Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days | First Course (n=120,109,85) | 16.04 days | Standard Deviation 5.52 |
| Rituximab Low Dose + Methotrexate | Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days | Second Course (n=116,99,85) | 19.62 days | Standard Deviation 6.05 |
| Rituximab Escalated Dose + Methotrexate | Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days | First Course (n=120,109,85) | 16.75 days | Standard Deviation 6.64 |
| Rituximab Escalated Dose + Methotrexate | Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days | Second Course (n=116,99,85) | 22.13 days | Standard Deviation 6.48 |
| Rituximab High Dose + Methotrexate | Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days | First Course (n=120,109,85) | 17.67 days | Standard Deviation 6 |
| Rituximab High Dose + Methotrexate | Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days | Second Course (n=116,99,85) | 21.42 days | Standard Deviation 6.32 |