Trial Outcomes & Findings for A Pharmacokinetic/Pharmacodynamic Study Comparing PF-05280586 To Rituximab In Subjects With Active Rheumatoid Arthritis With An Inadequate Response To TNF Inhibitors (REFLECTIONS B328-01) (NCT NCT01526057)

NCT ID: NCT01526057

Last Updated: 2019-11-19

Results Overview

Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

220 participants

Primary outcome timeframe

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

Results posted on

2019-11-19

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Rituximab-Pfizer Participants received intravenous (IV) rituximab (PF-05280586) infusion 1000 milligrams per 500 milliliters (preceded by 100 milligram \[mg\] 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 per week (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.	Rituximab-European Union (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.	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.
Overall Study STARTED	73	74	73
Overall Study COMPLETED	64	71	67
Overall Study NOT COMPLETED	9	3	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab-Pfizer Participants received intravenous (IV) rituximab (PF-05280586) infusion 1000 milligrams per 500 milliliters (preceded by 100 milligram \[mg\] 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 per week (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.	Rituximab-European Union (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.	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.
Overall Study Withdrawal by Subject	3	2	2
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

Baseline Characteristics

A Pharmacokinetic/Pharmacodynamic Study Comparing PF-05280586 To Rituximab In Subjects With Active Rheumatoid Arthritis With An Inadequate Response To TNF Inhibitors (REFLECTIONS B328-01)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.	Total n=220 Participants Total of all reporting groups
Age, Continuous	54.9 Years STANDARD_DEVIATION 11.52 • n=5 Participants	54.9 Years STANDARD_DEVIATION 11.07 • n=7 Participants	53.4 Years STANDARD_DEVIATION 11.87 • n=5 Participants	54.4 Years STANDARD_DEVIATION 11.46 • n=4 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	57 Participants n=7 Participants	54 Participants n=5 Participants	170 Participants n=4 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	17 Participants n=7 Participants	19 Participants n=5 Participants	50 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=68 Participants 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.	Rituximab-EU n=67 Participants 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.	Rituximab-US n=63 Participants 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.
Maximum Serum Concentration (Cmax) of Rituximab	453 micrograms per milliliter Standard Deviation 153	422 micrograms per milliliter Standard Deviation 111	430 micrograms per milliliter Standard Deviation 163

PRIMARY outcome

Population: PP population. "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=68 Participants 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.	Rituximab-EU n=67 Participants 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.	Rituximab-US n=62 Participants 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.
AUC 0-inf of Rituximab	213000 ug*hr/mL Standard Deviation 90400	200000 ug*hr/mL Standard Deviation 74500	214000 ug*hr/mL Standard Deviation 95300

SECONDARY outcome

Population: PP population.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=68 Participants 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.	Rituximab-EU n=67 Participants 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.	Rituximab-US n=63 Participants 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.
Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk)	52100 ug*hr/mL Standard Deviation 18000	49600 ug*hr/mL Standard Deviation 14200	49200 ug*hr/mL Standard Deviation 15900

SECONDARY outcome

Population: PP population.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=68 Participants 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.	Rituximab-EU n=67 Participants 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.	Rituximab-US n=63 Participants 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.
Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T)	198000 ug*hr/mL Standard Deviation 79600	188000 ug*hr/mL Standard Deviation 64300	196000 ug*hr/mL Standard Deviation 78300

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=68 Participants 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.	Rituximab-EU n=69 Participants 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.	Rituximab-US n=67 Participants 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.
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	14304 cells*day/mL Standard Deviation 13146	12496 cells*day/mL Standard Deviation 13500

SECONDARY outcome

Timeframe: 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.

The lowest CD19+ B-cell count measured in a participant's blood post-baseline.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=68 Participants 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.	Rituximab-EU n=69 Participants 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.	Rituximab-US n=67 Participants 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.
Minimum Post-Baseline CD19+ B-cell Count (/uL)	0.0 cells/uL Standard Deviation 0.28	0.0 cells/uL Standard Deviation 0.00	0.0 cells/uL Standard Deviation 0.18

SECONDARY outcome

Timeframe: 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.

The amount of time in weeks from baseline to the lowest observed CD19+ B-cell count.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=68 Participants 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.	Rituximab-EU n=69 Participants 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.	Rituximab-US n=67 Participants 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.
Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks)	1.4 weeks Standard Deviation 1.41	1.6 weeks Standard Deviation 1.68	1.5 weeks Standard Deviation 1.31

SECONDARY outcome

Timeframe: 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.

The τB-cell is defined as the time interval over which the B-cell count was \<0.3 cells/uL or the detection limit.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=68 Participants 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.	Rituximab-EU n=69 Participants 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.	Rituximab-US n=67 Participants 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.
Duration of B-cell Depletion (τB-cell) (Days)	126 days Standard Deviation 41.8	123 days Standard Deviation 38.6	120 days Standard Deviation 40.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=68 Participants 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.	Rituximab-EU n=69 Participants 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.	Rituximab-US n=67 Participants 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.
Percentage of Participants With CD19+ B-cell Count Recovery	4.4 Percentage of participants	8.7 Percentage of participants	9.0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=68 Participants 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.	Rituximab-EU n=69 Participants 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.	Rituximab-US n=67 Participants 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.
Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell)	13312.1 cells*day/uL Standard Deviation 13309.15	14304.2 cells*day/uL Standard Deviation 13145.72	12495.9 cells*day/uL Standard Deviation 13499.97

SECONDARY outcome

Timeframe: 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.

The level of IgM in serum at Baseline and the change from Baseline at each subsequent visit.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
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	1.460 g/L Standard Deviation 0.8076	1.394 g/L Standard Deviation 0.8372
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	0.0 g/L Standard Deviation 0.17	-0.0 g/L Standard Deviation 0.19
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	0.0 g/L Standard Deviation 0.17	0.0 g/L Standard Deviation 0.20
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	-0.1 g/L Standard Deviation 0.17	-0.0 g/L Standard Deviation 0.15
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	-0.1 g/L Standard Deviation 0.20	-0.0 g/L Standard Deviation 0.33
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	-0.1 g/L Standard Deviation 0.26	-0.1 g/L Standard Deviation 0.23
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	-0.3 g/L Standard Deviation 0.27	-0.2 g/L Standard Deviation 0.28
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	-0.3 g/L Standard Deviation 0.30	-0.2 g/L Standard Deviation 0.55
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	-0.3 g/L Standard Deviation 0.34	-0.3 g/L Standard Deviation 0.34
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	-0.4 g/L Standard Deviation 0.33	-0.3 g/L Standard Deviation 0.35
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	-0.3 g/L Standard Deviation 0.30	-0.3 g/L Standard Deviation 0.48

SECONDARY outcome

Timeframe: 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.

The percentage change from Baseline in circulating IgM by visit.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=72 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=70 Participants 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.
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) Week 21	-21.6 percent change Standard Deviation 17.72	-24.7 percent change Standard Deviation 21.00	-21.3 percent change Standard Deviation 15.69
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) Week 25	-24.2 percent change Standard Deviation 14.63	-21.0 percent change Standard Deviation 16.95	-20.5 percent change Standard Deviation 21.78
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) Week 1	3.3 percent change Standard Deviation 18.62	1.4 percent change Standard Deviation 9.57	-0.5 percent change Standard Deviation 9.93
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) Week 2	0.1 percent change Standard Deviation 12.45	-0.3 percent change Standard Deviation 9.42	0.7 percent change Standard Deviation 14.06
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) Week 3	-3.4 percent change Standard Deviation 12.98	-4.9 percent change Standard Deviation 9.95	-2.7 percent change Standard Deviation 9.82
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) Week 4	-5.5 percent change Standard Deviation 14.77	-5.0 percent change Standard Deviation 10.59	-2.2 percent change Standard Deviation 21.89
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) Week 5	-8.6 percent change Standard Deviation 16.00	-7.9 percent change Standard Deviation 15.60	-5.6 percent change Standard Deviation 14.39
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) Week 9	-14.4 percent change Standard Deviation 13.68	-16.9 percent change Standard Deviation 13.69	-14.1 percent change Standard Deviation 13.73
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) Week 13	-11.5 percent change Standard Deviation 37.17	-22.2 percent change Standard Deviation 13.92	-16.2 percent change Standard Deviation 30.14
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) Week 17	5.5 percent change Standard Deviation 226.39	-23.7 percent change Standard Deviation 16.35	-21.6 percent change Standard Deviation 14.88

SECONDARY outcome

Timeframe: Weeks 3, 5, 9, 13, 17, 21 and 25

Population: mITT population. "Number Analyzed" = participants evaluable at specified time points.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit Week 3	34.2 Percentage of participants	33.8 Percentage of participants	32.9 Percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit Week 5	54.8 Percentage of participants	56.8 Percentage of participants	42.5 Percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit Week 9	49.3 Percentage of participants	60.8 Percentage of participants	58.9 Percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit Week 13	50.7 Percentage of participants	70.3 Percentage of participants	63.0 Percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit Week 17	54.8 Percentage of participants	67.6 Percentage of participants	67.1 Percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit Week 21	54.2 Percentage of participants	62.2 Percentage of participants	69.4 Percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit Week 25	50.0 Percentage of participants	60.3 Percentage of participants	71.0 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 3, 5, 9, 13, 17, 21 and 25 (EOT)

Population: mITT population. "Number Analyzed" = participants evaluable at specified time points.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit Week 5	6.8 Percentage of participants	6.8 Percentage of participants	8.2 Percentage of participants
Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit Week 9	12.3 Percentage of participants	17.6 Percentage of participants	16.4 Percentage of participants
Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit Week 13	19.2 Percentage of participants	28.4 Percentage of participants	20.5 Percentage of participants
Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit Week 3	2.7 Percentage of participants	2.7 Percentage of participants	2.7 Percentage of participants
Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit Week 17	15.1 Percentage of participants	18.9 Percentage of participants	19.2 Percentage of participants
Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit Week 21	13.9 Percentage of participants	23.0 Percentage of participants	20.8 Percentage of participants
Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit Week 25	16.1 Percentage of participants	17.5 Percentage of participants	19.4 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 3, 5, 9, 13, 17, 21 and 25

Population: mITT population. "Number Analyzed" = participants evaluable at specified time points.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit Week 3	8.2 Percentage of Participants	5.4 Percentage of Participants	9.6 Percentage of Participants
Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit Week 5	19.2 Percentage of Participants	16.2 Percentage of Participants	20.5 Percentage of Participants
Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit Week 9	21.9 Percentage of Participants	32.4 Percentage of Participants	35.6 Percentage of Participants
Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit Week 13	35.6 Percentage of Participants	40.5 Percentage of Participants	31.5 Percentage of Participants
Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit Week 17	24.7 Percentage of Participants	36.5 Percentage of Participants	37.0 Percentage of Participants
Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit Week 21	27.8 Percentage of Participants	37.8 Percentage of Participants	38.9 Percentage of Participants
Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit Week 25	21.0 Percentage of Participants	38.1 Percentage of Participants	33.9 Percentage of Participants

SECONDARY outcome

Timeframe: Days 1 up to Day 169.

Population: mITT population.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
Percentage of Participants by Anti-drug Antibody (ADA) Status	9.6 Percentage of participants	13.5 Percentage of participants	12.3 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 up to Day 169

Population: mITT population. Only participants with a positive ADA status were included in the analysis.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=35 Participants 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.	Rituximab-EU n=39 Participants 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.	Rituximab-US n=34 Participants 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.
Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25

Population: mITT population. "Number Analyzed" = participants evaluable at specified time points.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
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	5.7928 Units on a scale Standard Deviation 0.9503	6.2221 Units on a scale Standard Deviation 0.88162
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	-0.8 Units on a scale Standard Deviation 1.13	-1.1 Units on a scale Standard Deviation 1.02
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	-1.4 Units on a scale Standard Deviation 1.06	-1.6 Units on a scale Standard Deviation 1.20
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	-1.8 Units on a scale Standard Deviation 1.3	-2.1 Units on a scale Standard Deviation 1.37
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	-2.1 Units on a scale Standard Deviation 1.33	-2.3 Units on a scale Standard Deviation 1.34
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	-2.1 Units on a scale Standard Deviation 1.39	-2.4 Units on a scale Standard Deviation 1.35
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	-1.9 Units on a scale Standard Deviation 1.33	-2.6 Units on a scale Standard Deviation 1.35
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	-2.0 Units on a scale Standard Deviation 1.30	-2.5 Units on a scale Standard Deviation 1.30

SECONDARY outcome

Timeframe: Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25

Population: mITT population. "Number Analyzed" = participants evaluable at specified time points.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
Percent Change From Baseline in DAS28-CRP by Visit Week 3	-16.1 Percent change Standard Deviation 19.08	-13.6 Percent change Standard Deviation 20.41	-18.6 Percent change Standard Deviation 17.63
Percent Change From Baseline in DAS28-CRP by Visit Week 5	-25.4 Percent change Standard Deviation 20.74	-24.0 Percent change Standard Deviation 18.22	-26.0 Percent change Standard Deviation 21.88
Percent Change From Baseline in DAS28-CRP by Visit Week 9	-31.2 Percent change Standard Deviation 22.31	-31.0 Percent change Standard Deviation 21.92	-34.2 Percent change Standard Deviation 22.97
Percent Change From Baseline in DAS28-CRP by Visit Week 13	-34.7 Percent change Standard Deviation 24.0	-36.9 Percent change Standard Deviation 22.1	-37.4 Percent change Standard Deviation 21.42
Percent Change From Baseline in DAS28-CRP by Visit Week 17	-34.9 Percent change Standard Deviation 22.65	-35.4 Percent change Standard Deviation 23.28	-39.1 Percent change Standard Deviation 21.35
Percent Change From Baseline in DAS28-CRP by Visit Week 21	-35.5 Percent change Standard Deviation 21.99	-33.4 Percent change Standard Deviation 22.56	-43.2 Percent change Standard Deviation 21.39
Percent Change From Baseline in DAS28-CRP by Visit Week 25	-31.1 Percent change Standard Deviation 22.72	-34.6 Percent change Standard Deviation 22.25	-40.0 Percent change Standard Deviation 20.55

SECONDARY outcome

Timeframe: Weeks 3, 5, 9, 13, 17, 21 and 25

Population: mITT population. "Number Analyzed" = participants evaluable at specified time points.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
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	10.8 Percentage of participants	8.7 Percentage of participants
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	22.5 Percentage of participants	19.4 Percentage of participants
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	31.5 Percentage of participants	25.7 Percentage of participants
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	44.4 Percentage of participants	32.8 Percentage of participants
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	38.0 Percentage of participants	32.8 Percentage of participants
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	35.4 Percentage of participants	47.5 Percentage of participants
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	36.2 Percentage of participants	41.8 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 3, 5, 9, 13, 17, 21 and 25

Population: mITT population. "Number Analyzed" = participants evaluable at specified time points.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit Week 3	33.3 Percentage of participants	35.1 Percentage of participants	42.0 Percentage of participants
Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit Week 5	47.9 Percentage of participants	39.4 Percentage of participants	43.3 Percentage of participants
Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit Week 9	45.6 Percentage of participants	43.8 Percentage of participants	54.3 Percentage of participants
Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit Week 13	38.8 Percentage of participants	37.5 Percentage of participants	44.8 Percentage of participants
Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit Week 17	45.5 Percentage of participants	39.4 Percentage of participants	53.7 Percentage of participants
Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit Week 21	51.7 Percentage of participants	46.2 Percentage of participants	39.0 Percentage of participants
Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit Week 25	50.0 Percentage of participants	46.6 Percentage of participants	43.6 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 3, 5, 9, 13, 17, 21 and 25

Population: mITT population. "Number Analyzed" = participants evaluable at specified time points.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
Percentage of Participants With No EULAR Response Based on DAS28 by Visit Week 3	52.2 Percentage of Participants	54.1 Percentage of Participants	49.3 Percentage of Participants
Percentage of Participants With No EULAR Response Based on DAS28 by Visit Week 5	29.6 Percentage of Participants	38.0 Percentage of Participants	37.3 Percentage of Participants
Percentage of Participants With No EULAR Response Based on DAS28 by Visit Week 9	23.5 Percentage of Participants	24.7 Percentage of Participants	20.0 Percentage of Participants
Percentage of Participants With No EULAR Response Based on DAS28 by Visit Week 13	19.4 Percentage of Participants	18.1 Percentage of Participants	22.4 Percentage of Participants
Percentage of Participants With No EULAR Response Based on DAS28 by Visit Week 17	18.2 Percentage of Participants	22.5 Percentage of Participants	13.4 Percentage of Participants
Percentage of Participants With No EULAR Response Based on DAS28 by Visit Week 21	13.3 Percentage of Participants	18.5 Percentage of Participants	13.6 Percentage of Participants
Percentage of Participants With No EULAR Response Based on DAS28 by Visit Week 25	20.0 Percentage of Participants	17.2 Percentage of Participants	14.5 Percentage of Participants

SECONDARY outcome

Timeframe: Weeks 3, 5, 9, 13, 17, 21 and 25

Population: mITT population. "Number Analyzed" = participants evaluable at specified time points.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit Week 3	14.5 Percentage of participants	10.8 Percentage of participants	10.1 Percentage of participants
Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit Week 5	23.9 Percentage of participants	25.4 Percentage of participants	19.4 Percentage of participants
Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit Week 9	30.9 Percentage of participants	32.9 Percentage of participants	25.7 Percentage of participants
Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit Week 13	41.8 Percentage of participants	44.4 Percentage of participants	32.8 Percentage of participants
Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit Week 17	36.4 Percentage of participants	38.0 Percentage of participants	32.8 Percentage of participants
Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit Week 21	35.0 Percentage of participants	36.9 Percentage of participants	47.5 Percentage of participants
Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit Week 25	32.0 Percentage of participants	37.9 Percentage of participants	41.8 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 3, 5, 9, 13, 17, 21 and 25

Population: mITT population. "Number Analyzed" = participants evaluable at specified time points.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
Percentage of Participants With DAS Remission (DAS <2.6) by Visit Week 3	8.7 Percentage of participants	4.1 Percentage of participants	7.2 Percentage of participants
Percentage of Participants With DAS Remission (DAS <2.6) by Visit Week 5	16.9 Percentage of participants	8.5 Percentage of participants	11.9 Percentage of participants
Percentage of Participants With DAS Remission (DAS <2.6) by Visit Week 9	26.5 Percentage of participants	20.5 Percentage of participants	20.0 Percentage of participants
Percentage of Participants With DAS Remission (DAS <2.6) by Visit Week 13	28.4 Percentage of participants	29.2 Percentage of participants	25.4 Percentage of participants
Percentage of Participants With DAS Remission (DAS <2.6) by Visit Week 17	25.8 Percentage of participants	25.4 Percentage of participants	23.9 Percentage of participants
Percentage of Participants With DAS Remission (DAS <2.6) by Visit Week 21	25.0 Percentage of participants	16.9 Percentage of participants	30.5 Percentage of participants
Percentage of Participants With DAS Remission (DAS <2.6) by Visit Week 25	28.0 Percentage of participants	24.1 Percentage of participants	23.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 3, 5, 9, 13, 17, 21 and 25

Population: mITT population. "Number Analyzed" = participants evaluable at specified time points.

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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=73 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit Baseline	1.6541 Units on a scale Standard Deviation 0.57340	1.5929 Units on a scale Standard Deviation 0.53597	1.7466 Units on a scale Standard Deviation 0.62081
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	-0.2 Units on a scale Standard Deviation 0.34	-0.2 Units on a scale Standard Deviation 0.33
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	-0.3 Units on a scale Standard Deviation 0.45	-0.3 Units on a scale Standard Deviation 0.43
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	-0.5 Units on a scale Standard Deviation 0.50	-0.5 Units on a scale Standard Deviation 0.54
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	-0.6 Units on a scale Standard Deviation 0.56	-0.5 Units on a scale Standard Deviation 0.52
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	-0.6 Units on a scale Standard Deviation 0.58	-0.5 Units on a scale Standard Deviation 0.55
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	-0.6 Units on a scale Standard Deviation 0.58	-0.6 Units on a scale Standard Deviation 0.61
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	-0.5 Units on a scale Standard Deviation 0.63	-0.6 Units on a scale Standard Deviation 0.57

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Rituximab-Pfizer n=72 Participants 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.	Rituximab-EU n=74 Participants 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.	Rituximab-US n=73 Participants 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.
Percent Change From Baseline in HAQ-DI Score by Visit Week 3	-10.4 Percentage change Standard Deviation 37.27	-13.2 Percentage change Standard Deviation 26.03	-9.0 Percentage change Standard Deviation 25.68
Percent Change From Baseline in HAQ-DI Score by Visit Week 5	-15.1 Percentage change Standard Deviation 40.00	-23.5 Percentage change Standard Deviation 30.45	-14.8 Percentage change Standard Deviation 43.82
Percent Change From Baseline in HAQ-DI Score by Visit Week 9	-22.4 Percentage change Standard Deviation 35.96	-31.7 Percentage change Standard Deviation 34.64	-24.5 Percentage change Standard Deviation 35.51
Percent Change From Baseline in HAQ-DI Score by Visit Week 13	-14.6 Percentage change Standard Deviation 50.35	-39.5 Percentage change Standard Deviation 37.46	-30.7 Percentage change Standard Deviation 31.91
Percent Change From Baseline in HAQ-DI Score by Visit Week 17	-16.9 Percentage change Standard Deviation 48.95	-39.1 Percentage change Standard Deviation 38.85	-28.8 Percentage change Standard Deviation 36.43
Percent Change From Baseline in HAQ-DI Score by Visit Week 21	-21.0 Percentage change Standard Deviation 48.04	-39.2 Percentage change Standard Deviation 38.34	-33.5 Percentage change Standard Deviation 35.18
Percent Change From Baseline in HAQ-DI Score by Visit Week 25	-17.7 Percentage change Standard Deviation 54.01	-37.1 Percentage change Standard Deviation 41.18	-38.4 Percentage change Standard Deviation 34.60

Adverse Events

Rituximab-Pfizer

Serious events: 5 serious events

Other events: 49 other events

Deaths: 0 deaths

Rituximab-EU

Serious events: 1 serious events

Other events: 40 other events

Deaths: 0 deaths

Rituximab-US

Serious events: 4 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab-Pfizer n=73 participants at risk 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.	Rituximab-EU n=74 participants at risk 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.	Rituximab-US n=73 participants at risk 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.
Blood and lymphatic system disorders Thrombocytopenic purpura	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.4% 1/74 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthropathy	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/74 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.4% 1/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone neoplasm	1.4% 1/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/74 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial flutter	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/74 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.4% 1/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure	1.4% 1/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/74 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure congestive	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/74 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.4% 1/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Arthritis bacterial	1.4% 1/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/74 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bacterial sepsis	1.4% 1/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/74 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pyelonephritis	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/74 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.4% 1/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Septic shock	1.4% 1/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/74 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Intentional self-injury	1.4% 1/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/74 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/73 • Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1. The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

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Principal investigator is a sponsor employee
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Restriction type: LTE60