Rheumatoid Arthritis
Conditions
Keywords
rheumatoid arthritis, rituximab, methotrexate, anti-TNF
Brief summary
In this study, patients with moderate to severe rheumatoid arthritis who are being treated with methotrexate will receive 2 intravenous treatments with either PF-05280586 or Rituxan (Rituximab) or MabThera (Rituximab). During the course of the study, the effects of the drugs will be assessed by sampling the levels of drug in the blood, blood cell counts, and by comparing these levels among the different treatments. Safety, tolerability and immunologic response also will be evaluated throughout.
Interventions
BIOLOGICALPF-05280586
1000 mg, IV on days 1 and 15
BIOLOGICALMabThera
1000 mg, IV on days 1 and 15
BIOLOGICALRituxan
1000 mg, IV on days 1 and 15
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of rheumatoid arthritis * Meets Class I, II or III of the ACR 1991 Revised Criteria * RA seropositivity * Stable dose of methotrexate * Inadequate response to TNF inhibitors
Exclusion criteria
* Any prior treatment with lymphocyte depleting therapies * History of active TB infection * Known or screen test positive for specific viruses or indicators of viral infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Rituximab | Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion | Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered. |
| AUC 0-inf of Rituximab | Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion | The AUC 0-inf refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) extrapolated to infinity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell) | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) | The AUC 0-T,B-cell refers to the concentration in serum of B-cells. It represents the total B-cells over time from time 0 (the point of drug administration) to the last measurement taken at time T. |
| Minimum Post-Baseline CD19+ B-cell Count (/uL) | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) | The lowest CD19+ B-cell count measured in a participant's blood post-baseline. |
| Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks) | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) | The amount of time in weeks from baseline to the lowest observed CD19+ B-cell count. |
| Duration of B-cell Depletion (τB-cell) (Days) | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) | The τB-cell is defined as the time interval over which the B-cell count was \<0.3 cells/uL or the detection limit. |
| Percentage of Participants With CD19+ B-cell Count Recovery | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 | The percentage of participants with CD19+ B-cell counts which fell to \<50% of Baseline value during treatment and which recovered to ≥50% of Baseline value at End of Treatment. |
| Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell) | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) | The AUC 0-T, B-cell refers to the CD19+ B-cell count over time. It represents the total B-cells over time, from time 0 (the point of drug administration) to the last measured count at time T. |
| Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25 (EOT) | The level of IgM in serum at Baseline and the change from Baseline at each subsequent visit. |
| Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25 | The percentage change from Baseline in circulating IgM by visit. |
| Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Weeks 3, 5, 9, 13, 17, 21 and 25 | ACR20 response: greater than or equal to (≥)20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participants who rolled over to the extension study were not included in the non-responder imputation from that point on. |
| Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Weeks 3, 5, 9, 13, 17, 21 and 25 (EOT) | ACR70 response: ≥70% improvement in tender joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participantss who rolled over to the extension study were not included in the non-responder imputation from that point on. |
| Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Weeks 3, 5, 9, 13, 17, 21 and 25 | ACR50 response: ≥50% improvement in tender joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participants who rolled over to the extension study were not included in the non-responder imputation from that point on. |
| Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk) | Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion | The AUC 0-2wk refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to 2 weeks after drug administration. |
| Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit | Day 1 up to Day 169 | — |
| Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25 | DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP less than or equal to (≤)3.2 implied low disease activity, DAS28-CRP greater than (\>)3.2 to ≤5.1 implied moderate to high disease activity, and DAS28-CRP less than (\<)2.6 implied remission. |
| Percent Change From Baseline in DAS28-CRP by Visit | Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25 | DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP less than or equal to (≤)3.2 implied low disease activity, DAS28-CRP greater than (\>)3.2 to ≤5.1 implied moderate to high disease activity, and DAS28-CRP less than (\<)2.6 implied remission. |
| Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Weeks 3, 5, 9, 13, 17, 21 and 25 | The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6, or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1. |
| Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Weeks 3, 5, 9, 13, 17, 21 and 25 | The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6, or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1. |
| Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Weeks 3, 5, 9, 13, 17, 21 and 25 | The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6, or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1. |
| Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Weeks 3, 5, 9, 13, 17, 21 and 25 | DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity. p-value of 9999 indicates p-value is not applicable. |
| Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Weeks 3, 5, 9, 13, 17, 21 and 25 | DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP \<2.6 implied remission. p-value of 9999 indicates p-value is not applicable. |
| Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Baseline, Week 3, 5, 9, 13, 17, 21 and 25 | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. |
| Percent Change From Baseline in HAQ-DI Score by Visit | Baseline, Week 3, 5, 9, 13, 17, 21 and 25 | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. |
| Percentage of Participants by Anti-drug Antibody (ADA) Status | Days 1 up to Day 169. | Presence of anti-rituximab antibodies in blood. Participants with a positive antibody status at any time during the study were defined as having overall positive antibody status; participants with a negative antibody status throughout the study were defined as having overall negative antibody status. |
| Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T) | Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion | The AUC 0-T refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to the last measured concentration at time T. |
Countries
Australia, Canada, Colombia, Germany, Israel, Mexico, Russia, South Africa, United Kingdom, United States
Participant flow
Recruitment details
This was a multinational, randomized, double-blind, controlled trial in participants with active rheumatoid arthritis (RA) on a background of methotrexate (MTX). The study was conducted at 56 centres in 10 countries. There were a total of 220 participants enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab-Pfizer Participants received IV rituximab (PF-05280586) infusion 1000 milligrams per 500 milliliters (preceded by 100 mg methylprednisolone, an antipyretic such as paracetamol, and an antihistamine such as diphenhydramine) on Day 1 and 15 and continued to receive a stable background regimen of methotrexate 10 to 25 mg/week (7.5 mg/week in the event of prior poor tolerance) for up to 25 weeks. Folate supplementation was encouraged according to local standard of care. | 73 |
| Rituximab-EU Participants received IV rituximab (MabThera) infusion 1000 milligrams per 500 milliliters (preceded by 100 mg methylprednisolone, an antipyretic such as paracetamol, and an antihistamine such as diphenhydramine) on Day 1 and 15 and continued to receive a stable background regimen of methotrexate 10 to 25 mg/week (7.5 mg/week in the event of prior poor tolerance) for up to 25 weeks. Folate supplementation was encouraged according to local standard of care. | 74 |
| Rituximab-US Participants received IV rituximab (Rituxan) infusion 1000 milligrams per 500 milliliters (preceded by 100 mg methylprednisolone, an antipyretic such as paracetamol, and an antihistamine such as diphenhydramine) on Day 1 and 15 and continued to receive a stable background regimen of methotrexate 10 to 25 mg/week (7.5 mg/week in the event of prior poor tolerance) for up to 25 weeks. Folate supplementation was encouraged according to local standard of care. | 73 |
| Total | 220 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 1 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Other | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 2 |
Baseline characteristics
| Characteristic | Rituximab-Pfizer | Rituximab-EU | Rituximab-US | Total |
|---|---|---|---|---|
| Age, Continuous | 54.9 Years STANDARD_DEVIATION 11.52 | 54.9 Years STANDARD_DEVIATION 11.07 | 53.4 Years STANDARD_DEVIATION 11.87 | 54.4 Years STANDARD_DEVIATION 11.46 |
| Sex: Female, Male Female | 59 Participants | 57 Participants | 54 Participants | 170 Participants |
| Sex: Female, Male Male | 14 Participants | 17 Participants | 19 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 49 / 73 | 40 / 74 | 45 / 73 |
| serious Total, serious adverse events | 5 / 73 | 1 / 74 | 4 / 73 |
Outcome results
Primary
AUC 0-inf of Rituximab
The AUC 0-inf refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) extrapolated to infinity.
Time frame: Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion
Population: PP population. Overall Number of Participants Analyzed= participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab-Pfizer | AUC 0-inf of Rituximab | 213000 ug*hr/mL | Standard Deviation 90400 |
| Rituximab-EU | AUC 0-inf of Rituximab | 200000 ug*hr/mL | Standard Deviation 74500 |
| Rituximab-US | AUC 0-inf of Rituximab | 214000 ug*hr/mL | Standard Deviation 95300 |
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way ANOVA model based on natural log-transformed data. The estimated differences for the log-transformed PK parameters were then transformed to relative ratios of PK parameters by exponentiation.90% CI: [92.75, 117.06]
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way ANOVA model based on natural log-transformed data. The estimated differences for the log-transformed PK parameters were then transformed to relative ratios of PK parameters by exponentiation.90% CI: [89.2, 113.11]
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way ANOVA model based on natural log-transformed data. The estimated differences for the log-transformed PK parameters were then transformed to relative ratios of PK parameters by exponentiation.90% CI: [85.57, 108.6]
Primary
Maximum Serum Concentration (Cmax) of Rituximab
Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered.
Time frame: Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion
Population: Per protocol (PP) population: all participants who were randomized, received the full doses of the assigned study treatment, and had no major protocol violations that could impact the pharmacokinetic (PK) analysis. Exclusions from the PP population were based on a blinded data review by the Medical Monitor and Clinical Pharmacologist.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab-Pfizer | Maximum Serum Concentration (Cmax) of Rituximab | 453 micrograms per milliliter | Standard Deviation 153 |
| Rituximab-EU | Maximum Serum Concentration (Cmax) of Rituximab | 422 micrograms per milliliter | Standard Deviation 111 |
| Rituximab-US | Maximum Serum Concentration (Cmax) of Rituximab | 430 micrograms per milliliter | Standard Deviation 163 |
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way analysis of variance (ANOVA) model based on natural log-transformed data. The estimated differences for the log-transformed PK parameters were then transformed to relative ratios of PK parameters by exponentiation.90% CI: [96.91, 115.21]
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way ANOVA model based on natural log-transformed data. The estimated differences for the log-transformed PK parameters were then transformed to relative ratios of PK parameters by exponentiation.90% CI: [97.65, 116.41]
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way ANOVA model based on natural log-transformed data. The estimated differences for the log-transformed PK parameters were then transformed to relative ratios of PK parameters by exponentiation.90% CI: [92.38, 110.2]
Secondary
Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell)
The AUC 0-T, B-cell refers to the CD19+ B-cell count over time. It represents the total B-cells over time, from time 0 (the point of drug administration) to the last measured count at time T.
Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Population: mITT population. Overall Number of Participants Analyzed= participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab-Pfizer | Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell) | 13312.1 cells*day/uL | Standard Deviation 13309.15 |
| Rituximab-EU | Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell) | 14304.2 cells*day/uL | Standard Deviation 13145.72 |
| Rituximab-US | Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell) | 12495.9 cells*day/uL | Standard Deviation 13499.97 |
Secondary
Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L])
The level of IgM in serum at Baseline and the change from Baseline at each subsequent visit.
Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25 (EOT)
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab-Pfizer | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 1 | 0.0 g/L | Standard Deviation 0.15 |
| Rituximab-Pfizer | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 21 | -0.3 g/L | Standard Deviation 0.42 |
| Rituximab-Pfizer | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 3 | -0.1 g/L | Standard Deviation 0.18 |
| Rituximab-Pfizer | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Baseline | 1.381 g/L | Standard Deviation 0.7617 |
| Rituximab-Pfizer | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 25 | -0.4 g/L | Standard Deviation 0.42 |
| Rituximab-Pfizer | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 5 | -0.1 g/L | Standard Deviation 0.3 |
| Rituximab-Pfizer | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 13 | -0.2 g/L | Standard Deviation 0.52 |
| Rituximab-Pfizer | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 9 | -0.2 g/L | Standard Deviation 0.32 |
| Rituximab-Pfizer | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 2 | 0.0 g/L | Standard Deviation 0.17 |
| Rituximab-Pfizer | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 17 | -0.1 g/L | Standard Deviation 0.92 |
| Rituximab-Pfizer | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 4 | -0.1 g/L | Standard Deviation 0.27 |
| Rituximab-EU | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 25 | -0.3 g/L | Standard Deviation 0.3 |
| Rituximab-EU | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 5 | -0.1 g/L | Standard Deviation 0.26 |
| Rituximab-EU | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 9 | -0.3 g/L | Standard Deviation 0.27 |
| Rituximab-EU | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 13 | -0.3 g/L | Standard Deviation 0.3 |
| Rituximab-EU | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 17 | -0.3 g/L | Standard Deviation 0.34 |
| Rituximab-EU | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 21 | -0.4 g/L | Standard Deviation 0.33 |
| Rituximab-EU | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Baseline | 1.460 g/L | Standard Deviation 0.8076 |
| Rituximab-EU | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 1 | 0.0 g/L | Standard Deviation 0.17 |
| Rituximab-EU | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 2 | 0.0 g/L | Standard Deviation 0.17 |
| Rituximab-EU | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 3 | -0.1 g/L | Standard Deviation 0.17 |
| Rituximab-EU | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 4 | -0.1 g/L | Standard Deviation 0.2 |
| Rituximab-US | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 3 | -0.0 g/L | Standard Deviation 0.15 |
| Rituximab-US | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 1 | -0.0 g/L | Standard Deviation 0.19 |
| Rituximab-US | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 13 | -0.2 g/L | Standard Deviation 0.55 |
| Rituximab-US | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 5 | -0.1 g/L | Standard Deviation 0.23 |
| Rituximab-US | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 2 | 0.0 g/L | Standard Deviation 0.2 |
| Rituximab-US | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 9 | -0.2 g/L | Standard Deviation 0.28 |
| Rituximab-US | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 25 | -0.3 g/L | Standard Deviation 0.48 |
| Rituximab-US | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 21 | -0.3 g/L | Standard Deviation 0.35 |
| Rituximab-US | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 4 | -0.0 g/L | Standard Deviation 0.33 |
| Rituximab-US | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Baseline | 1.394 g/L | Standard Deviation 0.8372 |
| Rituximab-US | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | Change from Baseline at Week 17 | -0.3 g/L | Standard Deviation 0.34 |
Secondary
CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell)
The AUC 0-T,B-cell refers to the concentration in serum of B-cells. It represents the total B-cells over time from time 0 (the point of drug administration) to the last measurement taken at time T.
Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Population: mITT population. Overall Number of Participants Analyzed= participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab-Pfizer | CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell) | 13312 cells*day/mL | Standard Deviation 13309 |
| Rituximab-EU | CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell) | 14304 cells*day/mL | Standard Deviation 13146 |
| Rituximab-US | CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell) | 12496 cells*day/mL | Standard Deviation 13500 |
Secondary
Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP)
DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP less than or equal to (≤)3.2 implied low disease activity, DAS28-CRP greater than (\>)3.2 to ≤5.1 implied moderate to high disease activity, and DAS28-CRP less than (\<)2.6 implied remission.
Time frame: Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab-Pfizer | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Baseline | 5.6862 Units on a scale | Standard Deviation 0.85109 |
| Rituximab-Pfizer | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 3 | -0.9 Units on a scale | Standard Deviation 1.01 |
| Rituximab-Pfizer | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 5 | -1.4 Units on a scale | Standard Deviation 1.17 |
| Rituximab-Pfizer | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 9 | -1.7 Units on a scale | Standard Deviation 1.29 |
| Rituximab-Pfizer | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 13 | -2.0 Units on a scale | Standard Deviation 1.43 |
| Rituximab-Pfizer | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 17 | -2.0 Units on a scale | Standard Deviation 1.32 |
| Rituximab-Pfizer | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 21 | -2.0 Units on a scale | Standard Deviation 1.28 |
| Rituximab-Pfizer | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 25 | -1.7 Units on a scale | Standard Deviation 1.25 |
| Rituximab-EU | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 5 | -1.4 Units on a scale | Standard Deviation 1.06 |
| Rituximab-EU | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 21 | -1.9 Units on a scale | Standard Deviation 1.33 |
| Rituximab-EU | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 9 | -1.8 Units on a scale | Standard Deviation 1.3 |
| Rituximab-EU | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 13 | -2.1 Units on a scale | Standard Deviation 1.33 |
| Rituximab-EU | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 17 | -2.1 Units on a scale | Standard Deviation 1.39 |
| Rituximab-EU | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Baseline | 5.7928 Units on a scale | Standard Deviation 0.9503 |
| Rituximab-EU | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 3 | -0.8 Units on a scale | Standard Deviation 1.13 |
| Rituximab-EU | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 25 | -2.0 Units on a scale | Standard Deviation 1.3 |
| Rituximab-US | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 5 | -1.6 Units on a scale | Standard Deviation 1.2 |
| Rituximab-US | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 3 | -1.1 Units on a scale | Standard Deviation 1.02 |
| Rituximab-US | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Baseline | 6.2221 Units on a scale | Standard Deviation 0.88162 |
| Rituximab-US | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 9 | -2.1 Units on a scale | Standard Deviation 1.37 |
| Rituximab-US | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 21 | -2.6 Units on a scale | Standard Deviation 1.35 |
| Rituximab-US | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 17 | -2.4 Units on a scale | Standard Deviation 1.35 |
| Rituximab-US | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 13 | -2.3 Units on a scale | Standard Deviation 1.34 |
| Rituximab-US | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | Change at Week 25 | -2.5 Units on a scale | Standard Deviation 1.3 |
Secondary
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time frame: Baseline, Week 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab-Pfizer | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Baseline | 1.6541 Units on a scale | Standard Deviation 0.5734 |
| Rituximab-Pfizer | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 3 | -0.2 Units on a scale | Standard Deviation 0.39 |
| Rituximab-Pfizer | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 5 | -0.3 Units on a scale | Standard Deviation 0.39 |
| Rituximab-Pfizer | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 9 | -0.4 Units on a scale | Standard Deviation 0.47 |
| Rituximab-Pfizer | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 13 | -0.4 Units on a scale | Standard Deviation 0.55 |
| Rituximab-Pfizer | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 17 | -0.3 Units on a scale | Standard Deviation 0.49 |
| Rituximab-Pfizer | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 21 | -0.4 Units on a scale | Standard Deviation 0.53 |
| Rituximab-Pfizer | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 25 | -0.4 Units on a scale | Standard Deviation 0.49 |
| Rituximab-EU | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 5 | -0.3 Units on a scale | Standard Deviation 0.45 |
| Rituximab-EU | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 21 | -0.6 Units on a scale | Standard Deviation 0.58 |
| Rituximab-EU | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 9 | -0.5 Units on a scale | Standard Deviation 0.5 |
| Rituximab-EU | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 13 | -0.6 Units on a scale | Standard Deviation 0.56 |
| Rituximab-EU | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 17 | -0.6 Units on a scale | Standard Deviation 0.58 |
| Rituximab-EU | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Baseline | 1.5929 Units on a scale | Standard Deviation 0.53597 |
| Rituximab-EU | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 3 | -0.2 Units on a scale | Standard Deviation 0.34 |
| Rituximab-EU | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 25 | -0.5 Units on a scale | Standard Deviation 0.63 |
| Rituximab-US | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 5 | -0.3 Units on a scale | Standard Deviation 0.43 |
| Rituximab-US | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 3 | -0.2 Units on a scale | Standard Deviation 0.33 |
| Rituximab-US | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Baseline | 1.7466 Units on a scale | Standard Deviation 0.62081 |
| Rituximab-US | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 9 | -0.5 Units on a scale | Standard Deviation 0.54 |
| Rituximab-US | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 21 | -0.6 Units on a scale | Standard Deviation 0.61 |
| Rituximab-US | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 17 | -0.5 Units on a scale | Standard Deviation 0.55 |
| Rituximab-US | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 13 | -0.5 Units on a scale | Standard Deviation 0.52 |
| Rituximab-US | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | Change at Week 25 | -0.6 Units on a scale | Standard Deviation 0.57 |
Secondary
Duration of B-cell Depletion (τB-cell) (Days)
The τB-cell is defined as the time interval over which the B-cell count was \<0.3 cells/uL or the detection limit.
Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Population: mITT population. Overall Number of Participants Analyzed= participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab-Pfizer | Duration of B-cell Depletion (τB-cell) (Days) | 126 days | Standard Deviation 41.8 |
| Rituximab-EU | Duration of B-cell Depletion (τB-cell) (Days) | 123 days | Standard Deviation 38.6 |
| Rituximab-US | Duration of B-cell Depletion (τB-cell) (Days) | 120 days | Standard Deviation 40.6 |
Secondary
Minimum Post-Baseline CD19+ B-cell Count (/uL)
The lowest CD19+ B-cell count measured in a participant's blood post-baseline.
Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Population: mITT population. Overall Number of Participants Analyzed= participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab-Pfizer | Minimum Post-Baseline CD19+ B-cell Count (/uL) | 0.0 cells/uL | Standard Deviation 0.28 |
| Rituximab-EU | Minimum Post-Baseline CD19+ B-cell Count (/uL) | 0.0 cells/uL | Standard Deviation 0 |
| Rituximab-US | Minimum Post-Baseline CD19+ B-cell Count (/uL) | 0.0 cells/uL | Standard Deviation 0.18 |
Secondary
Percentage of Participants by Anti-drug Antibody (ADA) Status
Presence of anti-rituximab antibodies in blood. Participants with a positive antibody status at any time during the study were defined as having overall positive antibody status; participants with a negative antibody status throughout the study were defined as having overall negative antibody status.
Time frame: Days 1 up to Day 169.
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab-Pfizer | Percentage of Participants by Anti-drug Antibody (ADA) Status | 9.6 Percentage of participants |
| Rituximab-EU | Percentage of Participants by Anti-drug Antibody (ADA) Status | 13.5 Percentage of participants |
| Rituximab-US | Percentage of Participants by Anti-drug Antibody (ADA) Status | 12.3 Percentage of participants |
Secondary
Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit
ACR50 response: ≥50% improvement in tender joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participants who rolled over to the extension study were not included in the non-responder imputation from that point on.
Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab-Pfizer | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 5 | 19.2 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 17 | 24.7 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 13 | 35.6 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 3 | 8.2 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 25 | 21.0 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 21 | 27.8 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 9 | 21.9 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 13 | 40.5 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 3 | 5.4 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 5 | 16.2 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 9 | 32.4 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 17 | 36.5 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 21 | 37.8 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 25 | 38.1 Percentage of Participants |
| Rituximab-US | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 17 | 37.0 Percentage of Participants |
| Rituximab-US | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 5 | 20.5 Percentage of Participants |
| Rituximab-US | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 25 | 33.9 Percentage of Participants |
| Rituximab-US | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 21 | 38.9 Percentage of Participants |
| Rituximab-US | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 13 | 31.5 Percentage of Participants |
| Rituximab-US | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 9 | 35.6 Percentage of Participants |
| Rituximab-US | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | Week 3 | 9.6 Percentage of Participants |
Secondary
Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit
ACR70 response: ≥70% improvement in tender joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participantss who rolled over to the extension study were not included in the non-responder imputation from that point on.
Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25 (EOT)
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab-Pfizer | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 5 | 6.8 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 17 | 15.1 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 13 | 19.2 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 3 | 2.7 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 25 | 16.1 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 21 | 13.9 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 9 | 12.3 Percentage of participants |
| Rituximab-EU | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 13 | 28.4 Percentage of participants |
| Rituximab-EU | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 3 | 2.7 Percentage of participants |
| Rituximab-EU | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 5 | 6.8 Percentage of participants |
| Rituximab-EU | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 9 | 17.6 Percentage of participants |
| Rituximab-EU | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 17 | 18.9 Percentage of participants |
| Rituximab-EU | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 21 | 23.0 Percentage of participants |
| Rituximab-EU | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 25 | 17.5 Percentage of participants |
| Rituximab-US | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 17 | 19.2 Percentage of participants |
| Rituximab-US | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 5 | 8.2 Percentage of participants |
| Rituximab-US | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 25 | 19.4 Percentage of participants |
| Rituximab-US | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 21 | 20.8 Percentage of participants |
| Rituximab-US | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 13 | 20.5 Percentage of participants |
| Rituximab-US | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 9 | 16.4 Percentage of participants |
| Rituximab-US | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | Week 3 | 2.7 Percentage of participants |
Secondary
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit
ACR20 response: greater than or equal to (≥)20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participants who rolled over to the extension study were not included in the non-responder imputation from that point on.
Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab-Pfizer | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 5 | 54.8 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 17 | 54.8 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 13 | 50.7 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 3 | 34.2 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 25 | 50.0 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 21 | 54.2 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 9 | 49.3 Percentage of participants |
| Rituximab-EU | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 13 | 70.3 Percentage of participants |
| Rituximab-EU | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 3 | 33.8 Percentage of participants |
| Rituximab-EU | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 5 | 56.8 Percentage of participants |
| Rituximab-EU | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 9 | 60.8 Percentage of participants |
| Rituximab-EU | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 17 | 67.6 Percentage of participants |
| Rituximab-EU | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 21 | 62.2 Percentage of participants |
| Rituximab-EU | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 25 | 60.3 Percentage of participants |
| Rituximab-US | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 17 | 67.1 Percentage of participants |
| Rituximab-US | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 5 | 42.5 Percentage of participants |
| Rituximab-US | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 25 | 71.0 Percentage of participants |
| Rituximab-US | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 21 | 69.4 Percentage of participants |
| Rituximab-US | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 13 | 63.0 Percentage of participants |
| Rituximab-US | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 9 | 58.9 Percentage of participants |
| Rituximab-US | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | Week 3 | 32.9 Percentage of participants |
Secondary
Percentage of Participants With CD19+ B-cell Count Recovery
The percentage of participants with CD19+ B-cell counts which fell to \<50% of Baseline value during treatment and which recovered to ≥50% of Baseline value at End of Treatment.
Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Overall Number of Participants Analyzed= participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab-Pfizer | Percentage of Participants With CD19+ B-cell Count Recovery | 4.4 Percentage of participants |
| Rituximab-EU | Percentage of Participants With CD19+ B-cell Count Recovery | 8.7 Percentage of participants |
| Rituximab-US | Percentage of Participants With CD19+ B-cell Count Recovery | 9.0 Percentage of participants |
Secondary
Percentage of Participants With DAS Remission (DAS <2.6) by Visit
DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP \<2.6 implied remission. p-value of 9999 indicates p-value is not applicable.
Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab-Pfizer | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 25 | 28.0 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 9 | 26.5 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 21 | 25.0 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 3 | 8.7 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 13 | 28.4 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 5 | 16.9 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 17 | 25.8 Percentage of participants |
| Rituximab-EU | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 3 | 4.1 Percentage of participants |
| Rituximab-EU | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 17 | 25.4 Percentage of participants |
| Rituximab-EU | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 21 | 16.9 Percentage of participants |
| Rituximab-EU | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 25 | 24.1 Percentage of participants |
| Rituximab-EU | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 5 | 8.5 Percentage of participants |
| Rituximab-EU | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 9 | 20.5 Percentage of participants |
| Rituximab-EU | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 13 | 29.2 Percentage of participants |
| Rituximab-US | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 25 | 23.6 Percentage of participants |
| Rituximab-US | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 5 | 11.9 Percentage of participants |
| Rituximab-US | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 3 | 7.2 Percentage of participants |
| Rituximab-US | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 9 | 20.0 Percentage of participants |
| Rituximab-US | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 13 | 25.4 Percentage of participants |
| Rituximab-US | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 17 | 23.9 Percentage of participants |
| Rituximab-US | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | Week 21 | 30.5 Percentage of participants |
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 3.95% CI: [0.12, 1.79]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 5.95% CI: [0.2, 1.26]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 9.95% CI: [0.43, 1.41]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 13.95% CI: [0.61, 1.74]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 17.95% CI: [0.56, 1.74]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 21.95% CI: [0.34, 1.36]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 25 (EOT).95% CI: [0.46, 1.63]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 3.95% CI: [0.27, 2.6]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 5.95% CI: [0.31, 1.62]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 9.95% CI: [0.41, 1.4]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 13.95% CI: [0.51, 1.57]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 17.95% CI: [0.51, 1.68]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 21.95% CI: [0.68, 2.19]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 25 (EOT).95% CI: [0.44, 1.62]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 3.95% CI: [0.44, 7.2]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 5.95% CI: [0.52, 3.86]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 9.95% CI: [0.51, 1.87]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 13.95% CI: [0.5, 1.5]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 17.95% CI: [0.52, 1.69]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 21.95% CI: [0.93, 3.5]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 25 (EOT).95% CI: [0.51, 1.89]
Secondary
Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit
The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6, or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1.
Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab-Pfizer | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 5 | 22.5 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 17 | 36.4 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 13 | 41.8 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 3 | 14.5 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 25 | 30.0 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 21 | 35.0 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 9 | 30.9 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 13 | 44.4 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 3 | 10.8 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 5 | 22.5 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 9 | 31.5 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 17 | 38.0 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 21 | 35.4 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 25 | 36.2 Percentage of participants |
| Rituximab-US | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 17 | 32.8 Percentage of participants |
| Rituximab-US | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 5 | 19.4 Percentage of participants |
| Rituximab-US | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 25 | 41.8 Percentage of participants |
| Rituximab-US | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 21 | 47.5 Percentage of participants |
| Rituximab-US | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 13 | 32.8 Percentage of participants |
| Rituximab-US | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 9 | 25.7 Percentage of participants |
| Rituximab-US | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | Week 3 | 8.7 Percentage of participants |
Secondary
Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit
DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity. p-value of 9999 indicates p-value is not applicable.
Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab-Pfizer | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 5 | 23.9 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 17 | 36.4 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 13 | 41.8 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 3 | 14.5 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 25 | 32.0 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 21 | 35.0 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 9 | 30.9 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 13 | 44.4 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 3 | 10.8 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 5 | 25.4 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 9 | 32.9 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 17 | 38.0 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 21 | 36.9 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 25 | 37.9 Percentage of participants |
| Rituximab-US | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 17 | 32.8 Percentage of participants |
| Rituximab-US | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 5 | 19.4 Percentage of participants |
| Rituximab-US | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 25 | 41.8 Percentage of participants |
| Rituximab-US | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 21 | 47.5 Percentage of participants |
| Rituximab-US | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 13 | 32.8 Percentage of participants |
| Rituximab-US | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 9 | 25.7 Percentage of participants |
| Rituximab-US | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | Week 3 | 10.1 Percentage of participants |
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 3.95% CI: [0.31, 1.78]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 5.95% CI: [0.6, 1.88]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 9.95% CI: [0.66, 1.73]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 13.95% CI: [0.73, 1.56]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 17.95% CI: [0.68, 1.62]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 21.95% CI: [0.66, 1.69]
Comparison: Statistical analysis of rituximab-EU versus rituximab-Pfizer at Week 25 (EOT).95% CI: [0.7, 2]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 3.95% CI: [0.28, 1.73]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 5.95% CI: [0.43, 1.54]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 9.95% CI: [0.49, 1.42]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 13.95% CI: [0.5, 1.22]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 17.95% CI: [0.57, 1.44]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 21.95% CI: [0.88, 2.1]
Comparison: Statistical analysis of rituximab-US versus rituximab-Pfizer at Week 25 (EOT).95% CI: [0.78, 2.18]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 3.95% CI: [0.36, 2.45]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 5.95% CI: [0.41, 1.44]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 9.95% CI: [0.47, 1.31]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 13.95% CI: [0.48, 1.13]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 17.95% CI: [0.55, 1.36]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 21.95% CI: [0.85, 1.95]
Comparison: Statistical analysis of rituximab-US versus rituximab-EU at Week 25 (EOT).95% CI: [0.7, 1.73]
Secondary
Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit
The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6, or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1.
Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab-Pfizer | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 25 | 50.0 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 17 | 45.5 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 13 | 38.8 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 5 | 47.9 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 3 | 33.3 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 21 | 51.7 Percentage of participants |
| Rituximab-Pfizer | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 9 | 45.6 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 3 | 35.1 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 5 | 39.4 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 9 | 43.8 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 13 | 37.5 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 17 | 39.4 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 21 | 46.2 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 25 | 46.6 Percentage of participants |
| Rituximab-US | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 17 | 53.7 Percentage of participants |
| Rituximab-US | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 5 | 43.3 Percentage of participants |
| Rituximab-US | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 25 | 43.6 Percentage of participants |
| Rituximab-US | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 21 | 39.0 Percentage of participants |
| Rituximab-US | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 13 | 44.8 Percentage of participants |
| Rituximab-US | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 9 | 54.3 Percentage of participants |
| Rituximab-US | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | Week 3 | 42.0 Percentage of participants |
Secondary
Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit
Time frame: Day 1 up to Day 169
Population: mITT population. Only participants with a positive ADA status were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab-Pfizer | Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit | 0.0 Percentage of participants |
| Rituximab-EU | Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit | 0.0 Percentage of participants |
| Rituximab-US | Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit | 0.0 Percentage of participants |
Secondary
Percentage of Participants With No EULAR Response Based on DAS28 by Visit
The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6, or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1.
Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab-Pfizer | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 5 | 29.6 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 17 | 18.2 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 13 | 19.4 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 3 | 52.2 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 25 | 20.0 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 21 | 13.3 Percentage of Participants |
| Rituximab-Pfizer | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 9 | 23.5 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 13 | 18.1 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 3 | 54.1 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 5 | 38.0 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 9 | 24.7 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 17 | 22.5 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 21 | 18.5 Percentage of Participants |
| Rituximab-EU | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 25 | 17.2 Percentage of Participants |
| Rituximab-US | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 17 | 13.4 Percentage of Participants |
| Rituximab-US | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 5 | 37.3 Percentage of Participants |
| Rituximab-US | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 25 | 14.5 Percentage of Participants |
| Rituximab-US | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 21 | 13.6 Percentage of Participants |
| Rituximab-US | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 13 | 22.4 Percentage of Participants |
| Rituximab-US | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 9 | 20.0 Percentage of Participants |
| Rituximab-US | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | Week 3 | 49.3 Percentage of Participants |
Secondary
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L)
The percentage change from Baseline in circulating IgM by visit.
Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25
Population: mITT population. Overall Number of Participants Analyzed= participants evaluable for this outcome measure. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab-Pfizer | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 13 | -11.5 percent change | Standard Deviation 37.17 |
| Rituximab-Pfizer | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 3 | -3.4 percent change | Standard Deviation 12.98 |
| Rituximab-Pfizer | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 17 | 5.5 percent change | Standard Deviation 226.39 |
| Rituximab-Pfizer | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 21 | -21.6 percent change | Standard Deviation 17.72 |
| Rituximab-Pfizer | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 1 | 3.3 percent change | Standard Deviation 18.62 |
| Rituximab-Pfizer | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 25 | -24.2 percent change | Standard Deviation 14.63 |
| Rituximab-Pfizer | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 4 | -5.5 percent change | Standard Deviation 14.77 |
| Rituximab-Pfizer | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 2 | 0.1 percent change | Standard Deviation 12.45 |
| Rituximab-Pfizer | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 5 | -8.6 percent change | Standard Deviation 16 |
| Rituximab-Pfizer | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 9 | -14.4 percent change | Standard Deviation 13.68 |
| Rituximab-EU | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 13 | -22.2 percent change | Standard Deviation 13.92 |
| Rituximab-EU | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 4 | -5.0 percent change | Standard Deviation 10.59 |
| Rituximab-EU | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 9 | -16.9 percent change | Standard Deviation 13.69 |
| Rituximab-EU | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 17 | -23.7 percent change | Standard Deviation 16.35 |
| Rituximab-EU | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 3 | -4.9 percent change | Standard Deviation 9.95 |
| Rituximab-EU | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 1 | 1.4 percent change | Standard Deviation 9.57 |
| Rituximab-EU | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 5 | -7.9 percent change | Standard Deviation 15.6 |
| Rituximab-EU | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 2 | -0.3 percent change | Standard Deviation 9.42 |
| Rituximab-EU | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 25 | -21.0 percent change | Standard Deviation 16.95 |
| Rituximab-EU | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 21 | -24.7 percent change | Standard Deviation 21 |
| Rituximab-US | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 25 | -20.5 percent change | Standard Deviation 21.78 |
| Rituximab-US | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 1 | -0.5 percent change | Standard Deviation 9.93 |
| Rituximab-US | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 2 | 0.7 percent change | Standard Deviation 14.06 |
| Rituximab-US | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 3 | -2.7 percent change | Standard Deviation 9.82 |
| Rituximab-US | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 4 | -2.2 percent change | Standard Deviation 21.89 |
| Rituximab-US | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 5 | -5.6 percent change | Standard Deviation 14.39 |
| Rituximab-US | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 9 | -14.1 percent change | Standard Deviation 13.73 |
| Rituximab-US | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 13 | -16.2 percent change | Standard Deviation 30.14 |
| Rituximab-US | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 17 | -21.6 percent change | Standard Deviation 14.88 |
| Rituximab-US | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | Week 21 | -21.3 percent change | Standard Deviation 15.69 |
Secondary
Percent Change From Baseline in DAS28-CRP by Visit
DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP less than or equal to (≤)3.2 implied low disease activity, DAS28-CRP greater than (\>)3.2 to ≤5.1 implied moderate to high disease activity, and DAS28-CRP less than (\<)2.6 implied remission.
Time frame: Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab-Pfizer | Percent Change From Baseline in DAS28-CRP by Visit | Week 5 | -25.4 Percent change | Standard Deviation 20.74 |
| Rituximab-Pfizer | Percent Change From Baseline in DAS28-CRP by Visit | Week 17 | -34.9 Percent change | Standard Deviation 22.65 |
| Rituximab-Pfizer | Percent Change From Baseline in DAS28-CRP by Visit | Week 13 | -34.7 Percent change | Standard Deviation 24 |
| Rituximab-Pfizer | Percent Change From Baseline in DAS28-CRP by Visit | Week 3 | -16.1 Percent change | Standard Deviation 19.08 |
| Rituximab-Pfizer | Percent Change From Baseline in DAS28-CRP by Visit | Week 25 | -31.1 Percent change | Standard Deviation 22.72 |
| Rituximab-Pfizer | Percent Change From Baseline in DAS28-CRP by Visit | Week 21 | -35.5 Percent change | Standard Deviation 21.99 |
| Rituximab-Pfizer | Percent Change From Baseline in DAS28-CRP by Visit | Week 9 | -31.2 Percent change | Standard Deviation 22.31 |
| Rituximab-EU | Percent Change From Baseline in DAS28-CRP by Visit | Week 13 | -36.9 Percent change | Standard Deviation 22.1 |
| Rituximab-EU | Percent Change From Baseline in DAS28-CRP by Visit | Week 3 | -13.6 Percent change | Standard Deviation 20.41 |
| Rituximab-EU | Percent Change From Baseline in DAS28-CRP by Visit | Week 5 | -24.0 Percent change | Standard Deviation 18.22 |
| Rituximab-EU | Percent Change From Baseline in DAS28-CRP by Visit | Week 9 | -31.0 Percent change | Standard Deviation 21.92 |
| Rituximab-EU | Percent Change From Baseline in DAS28-CRP by Visit | Week 17 | -35.4 Percent change | Standard Deviation 23.28 |
| Rituximab-EU | Percent Change From Baseline in DAS28-CRP by Visit | Week 21 | -33.4 Percent change | Standard Deviation 22.56 |
| Rituximab-EU | Percent Change From Baseline in DAS28-CRP by Visit | Week 25 | -34.6 Percent change | Standard Deviation 22.25 |
| Rituximab-US | Percent Change From Baseline in DAS28-CRP by Visit | Week 17 | -39.1 Percent change | Standard Deviation 21.35 |
| Rituximab-US | Percent Change From Baseline in DAS28-CRP by Visit | Week 5 | -26.0 Percent change | Standard Deviation 21.88 |
| Rituximab-US | Percent Change From Baseline in DAS28-CRP by Visit | Week 25 | -40.0 Percent change | Standard Deviation 20.55 |
| Rituximab-US | Percent Change From Baseline in DAS28-CRP by Visit | Week 21 | -43.2 Percent change | Standard Deviation 21.39 |
| Rituximab-US | Percent Change From Baseline in DAS28-CRP by Visit | Week 13 | -37.4 Percent change | Standard Deviation 21.42 |
| Rituximab-US | Percent Change From Baseline in DAS28-CRP by Visit | Week 9 | -34.2 Percent change | Standard Deviation 22.97 |
| Rituximab-US | Percent Change From Baseline in DAS28-CRP by Visit | Week 3 | -18.6 Percent change | Standard Deviation 17.63 |
Secondary
Percent Change From Baseline in HAQ-DI Score by Visit
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time frame: Baseline, Week 3, 5, 9, 13, 17, 21 and 25
Population: mITT population. Overall Number of Participants Analyzed= participants evaluable for this outcome measure. Number Analyzed = participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab-Pfizer | Percent Change From Baseline in HAQ-DI Score by Visit | Week 17 | -16.9 Percentage change | Standard Deviation 48.95 |
| Rituximab-Pfizer | Percent Change From Baseline in HAQ-DI Score by Visit | Week 9 | -22.4 Percentage change | Standard Deviation 35.96 |
| Rituximab-Pfizer | Percent Change From Baseline in HAQ-DI Score by Visit | Week 13 | -14.6 Percentage change | Standard Deviation 50.35 |
| Rituximab-Pfizer | Percent Change From Baseline in HAQ-DI Score by Visit | Week 25 | -17.7 Percentage change | Standard Deviation 54.01 |
| Rituximab-Pfizer | Percent Change From Baseline in HAQ-DI Score by Visit | Week 21 | -21.0 Percentage change | Standard Deviation 48.04 |
| Rituximab-Pfizer | Percent Change From Baseline in HAQ-DI Score by Visit | Week 5 | -15.1 Percentage change | Standard Deviation 40 |
| Rituximab-Pfizer | Percent Change From Baseline in HAQ-DI Score by Visit | Week 3 | -10.4 Percentage change | Standard Deviation 37.27 |
| Rituximab-EU | Percent Change From Baseline in HAQ-DI Score by Visit | Week 9 | -31.7 Percentage change | Standard Deviation 34.64 |
| Rituximab-EU | Percent Change From Baseline in HAQ-DI Score by Visit | Week 3 | -13.2 Percentage change | Standard Deviation 26.03 |
| Rituximab-EU | Percent Change From Baseline in HAQ-DI Score by Visit | Week 5 | -23.5 Percentage change | Standard Deviation 30.45 |
| Rituximab-EU | Percent Change From Baseline in HAQ-DI Score by Visit | Week 13 | -39.5 Percentage change | Standard Deviation 37.46 |
| Rituximab-EU | Percent Change From Baseline in HAQ-DI Score by Visit | Week 17 | -39.1 Percentage change | Standard Deviation 38.85 |
| Rituximab-EU | Percent Change From Baseline in HAQ-DI Score by Visit | Week 21 | -39.2 Percentage change | Standard Deviation 38.34 |
| Rituximab-EU | Percent Change From Baseline in HAQ-DI Score by Visit | Week 25 | -37.1 Percentage change | Standard Deviation 41.18 |
| Rituximab-US | Percent Change From Baseline in HAQ-DI Score by Visit | Week 17 | -28.8 Percentage change | Standard Deviation 36.43 |
| Rituximab-US | Percent Change From Baseline in HAQ-DI Score by Visit | Week 3 | -9.0 Percentage change | Standard Deviation 25.68 |
| Rituximab-US | Percent Change From Baseline in HAQ-DI Score by Visit | Week 25 | -38.4 Percentage change | Standard Deviation 34.6 |
| Rituximab-US | Percent Change From Baseline in HAQ-DI Score by Visit | Week 21 | -33.5 Percentage change | Standard Deviation 35.18 |
| Rituximab-US | Percent Change From Baseline in HAQ-DI Score by Visit | Week 13 | -30.7 Percentage change | Standard Deviation 31.91 |
| Rituximab-US | Percent Change From Baseline in HAQ-DI Score by Visit | Week 5 | -14.8 Percentage change | Standard Deviation 43.82 |
| Rituximab-US | Percent Change From Baseline in HAQ-DI Score by Visit | Week 9 | -24.5 Percentage change | Standard Deviation 35.51 |
Secondary
Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk)
The AUC 0-2wk refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to 2 weeks after drug administration.
Time frame: Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion
Population: PP population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab-Pfizer | Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk) | 52100 ug*hr/mL | Standard Deviation 18000 |
| Rituximab-EU | Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk) | 49600 ug*hr/mL | Standard Deviation 14200 |
| Rituximab-US | Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk) | 49200 ug*hr/mL | Standard Deviation 15900 |
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way ANOVA model based on natural log-transformed data. The estimated differences for the log-transformed PK parameters were then transformed to relative ratios of PK parameters by exponentiation.90% CI: [95.1, 113.12]
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way ANOVA model based on natural log-transformed data. The estimated differences for the log-transformed PK parameters were then transformed to relative ratios of PK parameters by exponentiation.90% CI: [96.64, 115.3]
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way ANOVA model based on natural log-transformed data.90% CI: [93.13, 111.18]
Secondary
Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T)
The AUC 0-T refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to the last measured concentration at time T.
Time frame: Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion
Population: PP population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab-Pfizer | Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T) | 198000 ug*hr/mL | Standard Deviation 79600 |
| Rituximab-EU | Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T) | 188000 ug*hr/mL | Standard Deviation 64300 |
| Rituximab-US | Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T) | 196000 ug*hr/mL | Standard Deviation 78300 |
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way ANOVA model based on natural log-transformed data. The estimated differences for the log-transformed PK parameters were then transformed to relative ratios of PK parameters by exponentiation.90% CI: [92.81, 115.12]
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way ANOVA model based on natural log-transformed data. The estimated differences for the log-transformed PK parameters were then transformed to relative ratios of PK parameters by exponentiation.90% CI: [90.82, 113.04]
Comparison: A 90% CI on the estimated difference between 2 treatment groups was constructed using a 1-way ANOVA model based on natural log-transformed data. The estimated differences for the log-transformed PK parameters were then transformed to relative ratios of PK parameters by exponentiation.90% CI: [87.83, 109.4]
Secondary
Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks)
The amount of time in weeks from baseline to the lowest observed CD19+ B-cell count.
Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Population: mITT population. Overall Number of Participants Analyzed= participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab-Pfizer | Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks) | 1.4 weeks | Standard Deviation 1.41 |
| Rituximab-EU | Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks) | 1.6 weeks | Standard Deviation 1.68 |
| Rituximab-US | Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks) | 1.5 weeks | Standard Deviation 1.31 |