Trial Outcomes & Findings for A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on One Prior Anti-TNF Therapy (RESET) (NCT NCT01272908)

Results Overview

Percentage of participants who reported an AE or serious AE (SAE), a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

120 participants

Primary outcome timeframe

Days 1, 2, 15, and 16 and Week 48 of Initial treatment period

Results posted on

2017-08-15

Participant Flow

Participant milestones

Participant milestones
Measure	Rituximab + Methotrexate (MTX) Participants received rituximab 1000 milligrams (mg) intravenously (IV) and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg per week (mg/week) and a stable dose of folate (greater than or equal to \[≥\]5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (Disease Activity Score based on 28-Joint Count \[DAS28\] score of greater than or equal to \[≥\]2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\], given 14 days apart), at any time between Week 24 and 48.
Initial Treatment Period STARTED	120
Initial Treatment Period COMPLETED	112
Initial Treatment Period NOT COMPLETED	8
Re-Treatment Period STARTED	77
Re-Treatment Period COMPLETED	71
Re-Treatment Period NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab + Methotrexate (MTX) Participants received rituximab 1000 milligrams (mg) intravenously (IV) and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg per week (mg/week) and a stable dose of folate (greater than or equal to \[≥\]5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (Disease Activity Score based on 28-Joint Count \[DAS28\] score of greater than or equal to \[≥\]2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\], given 14 days apart), at any time between Week 24 and 48.
Initial Treatment Period Adverse Event	1
Initial Treatment Period Lack of Efficacy	5
Initial Treatment Period Protocol Violation	1
Initial Treatment Period Withdrawal by Subject	1
Re-Treatment Period Adverse Event	2
Re-Treatment Period Lack of Efficacy	3
Re-Treatment Period Withdrawal by Subject	1

Baseline Characteristics

A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on One Prior Anti-TNF Therapy (RESET)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Age, Continuous	55.6 years STANDARD_DEVIATION 10.20 • n=5 Participants
Sex: Female, Male Female	87 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants

PRIMARY outcome

Timeframe: Days 1, 2, 15, and 16 and Week 48 of Initial treatment period

Population: ITT Population

Percentage of participants who reported an AE or serious AE (SAE), a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary With an AE	85.0 percentage of participants
Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary With a drug-related AE	41.7 percentage of participants
Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary With an acute infusion reaction	20.8 percentage of participants
Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary With AE leading to study drug discontinuation	4.2 percentage of participants
Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary With an SAE	10.0 percentage of participants
Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary With infections	47.5 percentage of participants
Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary With a serious infections	2.5 percentage of participants
Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary Who died	0 percentage of participants

SECONDARY outcome

Timeframe: Days 1, 2, 15, and 16 and Week 48 of Re-treatment period

Population: ITT Population

Percentage of participants who reported an AE or SAE, a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=77 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary With infections	27.3 percentage of participants
Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary With an AE	68.8 percentage of participants
Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary With a drug-related AE	27.3 percentage of participants
Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary With an acute infusion reaction	13.0 percentage of participants
Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary With AE leading to study drug discontinuation	1.3 percentage of participants
Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary With an SAE	9.1 percentage of participants
Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary With a serious infections	2.6 percentage of participants
Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary Who died	0 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population

ACR20/50/70, defined as ≥20 percent (%), 50%, or 70% improvement, respectively, compared to baseline in tender joint count (TJC) and swollen joint count (SJC), and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and an acute phase reactant (erythrocyte sedimentation rate \[ESR\] or C-Reactive Protein \[CRP\]). If CRP was missing or not done, then ESR was used.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR50, Week 12	22.5 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR20, Week 4	31.7 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR20, Week 12	50.0 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR20, Week 24	54.2 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR20, Week 36	25.0 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR20, Week 48	15.8 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR50, Week 4	5.8 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR50, Week 24	25.0 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR50, Week 36	11.7 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR50, Week 48	9.2 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR70, Week 4	0 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR70, Week 12	4.2 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR70, Week 24	5.8 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR70, Week 36	5.8 percentage of participants
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period ACR70, Week 48	4.2 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population

Complete clinical response was defined as having an ACR70 for at least 13 weeks.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Initial Treatment Period	4.2 percentage of participants

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population

ACR20/50/70, defined as ≥20%, 50%, or 70% improvement, respectively, compared to baseline in TJC and SJC, and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; HAQ-DI; and an acute phase reactant (ESR or CRP). If CRP was missing or not done, then ESR was used.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=77 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period ACR50, Week 12	26.0 percentage of participants
Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period ACR20, Week 12	54.5 percentage of participants
Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period ACR20, Week 24	58.4 percentage of participants
Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period ACR50, Week 24	28.6 percentage of participants
Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period ACR70, Week 12	6.5 percentage of participants
Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period ACR70, Week 24	9.1 percentage of participants

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population

Complete clinical response was defined as having an ACR70 for at least 13 weeks.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=77 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Re-Treatment Period	1.3 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population

The EULAR response criteria were based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score less than or equal to \[≤\]3.2), moderate (DAS28 score greater than \[\>\]3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 4: Good	4.2 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 4: Moderate	47.5 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 4: Good/Moderate	51.7 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 4: None	46.7 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 12: Good	9.2 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 12: Moderate	55.0 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 12: Good/Moderate	64.2 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 12: None	33.3 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 24: Good	17.5 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 24: Moderate	50.0 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 24: Good/Moderate	67.5 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 24: None	26.7 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 36: Good	10.8 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 36: Moderate	24.2 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 36: Good/Moderate	35.0 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 36: None	23.3 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 48: Good	8.3 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 48: Moderate	10.8 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 48: Good/Moderate	19.2 percentage of participants
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period Week 48: None	10.0 percentage of participants

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population

The EULAR response criteria were based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=77 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period Week 12: Good	20.8 percentage of participants
Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period Week 12: Moderate	53.2 percentage of participants
Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period Week 12: Good/Moderate	74.0 percentage of participants
Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period Week 12: None	22.1 percentage of participants
Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period Week 24: Good	19.5 percentage of participants
Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period Week 24: Moderate	48.1 percentage of participants
Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period Week 24: Good/Moderate	67.5 percentage of participants
Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period Week 24: None	26.0 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population; n (number) = number of participants assessed for the specified parameter at a given visit.

The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria. A change of 1.2 units in DAS28 in an individual participant was considered a significant change.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=117 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in DAS28 During the Initial Treatment Period Baseline (n=117)	6.4 scores on a scale Standard Deviation 1.1
Change From Baseline in DAS28 During the Initial Treatment Period Change at Week 4 (n=112)	-1.1 scores on a scale Standard Deviation 0.8
Change From Baseline in DAS28 During the Initial Treatment Period Change at Week 12 (n=108)	-1.7 scores on a scale Standard Deviation 1.2
Change From Baseline in DAS28 During the Initial Treatment Period Change at Week 24 (n=105)	-2.0 scores on a scale Standard Deviation 1.2
Change From Baseline in DAS28 During the Initial Treatment Period Change at Week 36 (n=66)	-1.7 scores on a scale Standard Deviation 1.7
Change From Baseline in DAS28 During the Initial Treatment Period Change at Week 48 (n=33)	-2.1 scores on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

The DAS28 scoring used 4 core components: SJC, TJC, Patient Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score \<2.6 corresponded to a state of remission according to American Rheumatism Association criteria. A change of 1.2 units in DAS28 in an individual participant was considered a significant change.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=117 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in DAS28 During the Re-Treatment Period Baseline (n=117)	6.4 scores on a scale Standard Deviation 1.1
Change From Baseline in DAS28 During the Re-Treatment Period Change at Week 12 (n=70)	-2.3 scores on a scale Standard Deviation 1.3
Change From Baseline in DAS28 During the Re-Treatment Period Change at Week 24 (n=65)	-2.2 scores on a scale Standard Deviation 1.4

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=117 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in SJC During the Initial Treatment Period Baseline (n=117)	13.7 swollen joints Standard Deviation 5.33
Change From Baseline in SJC During the Initial Treatment Period Change at Week 4 (n=115)	-3.6 swollen joints Standard Deviation 4.45
Change From Baseline in SJC During the Initial Treatment Period Change at Week 12 (n=113)	-5.7 swollen joints Standard Deviation 4.97
Change From Baseline in SJC During the Initial Treatment Period Change at Week 24 (n=106)	-7.1 swollen joints Standard Deviation 5.66
Change From Baseline in SJC During the Initial Treatment Period Change at Week 36 (n=67)	-5.6 swollen joints Standard Deviation 6.50
Change From Baseline in SJC During the Initial Treatment Period Change at Week 48 (n=33)	-7.7 swollen joints Standard Deviation 5.56

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given vist.

Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=117 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in SJC During the Re-Treatment Period Baseline (n=117)	13.7 swollen joints Standard Deviation 5.33
Change From Baseline in SJC During the Re-Treatment Period Change at Week 12 (n=71)	-7.6 swollen joints Standard Deviation 6.07
Change From Baseline in SJC During the Re-Treatment Period Change at Week 24 (n=69)	-7.7 swollen joints Standard Deviation 5.43

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population; n=number of participants assessed for the specific parameter at a given visit.

Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=117 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in TJC During the Initial Treatment Period Baseline (n=117)	16.1 tender joints Standard Deviation 6.62
Change From Baseline in TJC During the Initial Treatment Period Change at Week 4 (n=115)	-6.3 tender joints Standard Deviation 5.95
Change From Baseline in TJC During the Initial Treatment Period Change at Week 12 (n=113)	-7.8 tender joints Standard Deviation 6.68
Change From Baseline in TJC During the Initial Treatment Period Change at Week 24 (n=106)	-9.0 tender joints Standard Deviation 6.42
Change From Baseline in TJC During the Initial Treatment Period Change at Week 36 (n=67)	-7.4 tender joints Standard Deviation 8.35
Change From Baseline in TJC During the Initial Treatment Period Change at Week 48 (n=33)	-7.8 tender joints Standard Deviation 8.31

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=117 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in TJC During the Re-Treatment Period Baseline (n=117)	16.1 tender joints Standard Deviation 6.62
Change From Baseline in TJC During the Re-Treatment Period Change at Week 12 (n=71)	-9.4 tender joints Standard Deviation 7.54
Change From Baseline in TJC During the Re-Treatment Period Change at Week 24 (n=69)	-9.7 tender joints Standard Deviation 6.92

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

Physician Global Assessment of Disease Activity was measured using a 100-mm visual analog scale (VAS) where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The physician marked the line and the distance from the left edge was measured in mm.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period Baseline (n=120)	68.6 mm Standard Deviation 17.34
Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period Change at Week 4 (n=117)	-22.0 mm Standard Deviation 21.67
Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period Change at Week 12 (n=116)	-31.4 mm Standard Deviation 24.28
Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period Change at Week 24 (n=109)	-35.1 mm Standard Deviation 24.45
Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period Change at Week 36 (n=68)	-28.6 mm Standard Deviation 28.68
Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period Change at Week 48 (n=34)	-35.9 mm Standard Deviation 25.18

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

Physician Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The physician marked the line and the distance from the left edge was measured in mm.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period Baseline (n=120)	68.6 mm Standard Deviation 17.34
Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period Change at Week 12 (n=73)	-35.5 mm Standard Deviation 25.95
Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period Change at Week 24 (n=69)	-41.5 mm Standard Deviation 24.43

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The participant was asked to marked the line and the distance from the left edge was measured in mm.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period Baseline (n=120)	67.5 mm Standard Deviation 22.73
Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period Change at Week 4 (n=117)	-19.7 mm Standard Deviation 21.50
Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period Change at Week 12 (n=116)	-26.3 mm Standard Deviation 26.84
Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period Change at Week 24 (n=109)	-29.2 mm Standard Deviation 25.72
Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period Change at Week 36 (n=68)	-23.8 mm Standard Deviation 30.42
Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period Change at Week 48 (n=34)	-28.5 mm Standard Deviation 22.92

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period and Week 4 after last maintenance

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The participant was asked to marked the line and the distance from the left edge was measured in mm.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period Baseline (n=120)	67.5 mm Standard Deviation 22.73
Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period Change at Week 12 (n=72)	-32.6 mm Standard Deviation 29.20
Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period Change at Week 24 (n=72)	-30.7 mm Standard Deviation 28.70

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain. The participant was asked to mark the line and the distance from the left edge was measured in mm.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period Baseline (n=120)	60.2 mm Standard Deviation 22.85
Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period Change at Week 4 (n=117)	-17.5 mm Standard Deviation 21.80
Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period Change at Week 12 (n=113)	-24.0 mm Standard Deviation 25.31
Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period Change at Week 24 (n=108)	-25.7 mm Standard Deviation 25.40
Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period Change at Week 36 (n=68)	-18.0 mm Standard Deviation 29.18
Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period Change at Week 48 (n=33)	-22.6 mm Standard Deviation 20.07

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain. The participant was asked to mark the line and the distance from the left edge was measured in mm.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period Baseline (n=120)	60.2 mm Standard Deviation 22.85
Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period Change at Week 12 (n=72)	-28.3 mm Standard Deviation 28.02
Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period Change at Week 24 (n=72)	-26.6 mm Standard Deviation 27.61

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities. Participants report amount of difficulty in performing 2-3 specific subcategory items. Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do). The highest component score in each of the 8 categories determined the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3). The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability). HAQ-DI not computed if \> 2 categories were missing.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline HAQ-DI Score During the Initial Treatment Period Baseline (n=120)	1.7 scores on a scale Standard Deviation 0.57
Change From Baseline HAQ-DI Score During the Initial Treatment Period Change at Week 4 (n=117)	-0.2 scores on a scale Standard Deviation 0.36
Change From Baseline HAQ-DI Score During the Initial Treatment Period Change at Week 12 (n=116)	-0.3 scores on a scale Standard Deviation 0.46
Change From Baseline HAQ-DI Score During the Initial Treatment Period Change at Week 24 (n=108)	-0.4 scores on a scale Standard Deviation 0.48
Change From Baseline HAQ-DI Score During the Initial Treatment Period Change at Week 36 (n=68)	-0.3 scores on a scale Standard Deviation 0.53
Change From Baseline HAQ-DI Score During the Initial Treatment Period Change at Week 48 (n=34)	-0.4 scores on a scale Standard Deviation 0.56

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities. Participants report amount of difficulty in performing 2-3 specific subcategory items. Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do). The highest component score in each of the 8 categories determines the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3). The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability). HAQ-DI not computed if \>2 categories were missing.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline HAQ-DI Score During the Re-Treatment Period Baseline (n=120)	1.7 scores on a scale Standard Deviation 0.57
Change From Baseline HAQ-DI Score During the Re-Treatment Period Change at Week 12 (n=73)	-0.5 scores on a scale Standard Deviation 0.60
Change From Baseline HAQ-DI Score During the Re-Treatment Period Change at Week 24 (n=72)	-0.5 scores on a scale Standard Deviation 0.62

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

ESR was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in ESR During the Initial Treatment Period Baseline (n=120)	37.0 mm/hr Standard Deviation 27.84
Change From Baseline in ESR During the Initial Treatment Period Change at Week 4 (n=112)	-4.5 mm/hr Standard Deviation 13.57
Change From Baseline in ESR During the Initial Treatment Period Change at Week 12 (n=112)	-11.3 mm/hr Standard Deviation 20.60
Change From Baseline in ESR During the Initial Treatment Period Change at Week 24 (n=107)	-16.0 mm/hr Standard Deviation 20.36
Change From Baseline in ESR During the Initial Treatment Period Change at Week 36 (n=68)	-9.2 mm/hr Standard Deviation 22.29
Change From Baseline in ESR During the Initial Treatment Period Change at Week 48 (n=34)	-12.0 mm/hr Standard Deviation 17.93

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

ESR was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in ESR During the Re-Treatment Period Baseline (n=120)	37.0 mm/hr Standard Deviation 27.84
Change From Baseline in ESR During the Re-Treatment Period Change at Week 12 (n=73)	-17.9 mm/hr Standard Deviation 22.07
Change From Baseline in ESR During the Re-Treatment Period Change at Week 24 (n=67)	-18.7 mm/hr Standard Deviation 23.05

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

CRP levels were measured in milligrams/liter (mg/L) and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=119 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in CRP During the Initial Treatment Period Baseline (n=119)	25.6 mg/L Standard Deviation 28.87
Change From Baseline in CRP During the Initial Treatment Period Change at Week 4 (n=110)	-7.9 mg/L Standard Deviation 17.44
Change From Baseline in CRP During the Initial Treatment Period Change at Week 12 (n=113)	-11.9 mg/L Standard Deviation 31.97
Change From Baseline in CRP During the Initial Treatment Period Change at Week 24 (n=108)	-16.1 mg/L Standard Deviation 24.82
Change From Baseline in CRP During the Initial Treatment Period Change at Week 36 (n=67)	-9.1 mg/L Standard Deviation 25.74
Change From Baseline in CRP During the Initial Treatment Period Change at Week 48 (n=34)	-7.6 mg/L Standard Deviation 27.06

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

CRP levels were measured in mg/L and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=119 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline CRP During the Re-Treatment Period Baseline (n=119)	25.6 mg/L Standard Deviation 28.87
Change From Baseline CRP During the Re-Treatment Period Change at Week 12 (n=70)	-16.9 mg/L Standard Deviation 27.15
Change From Baseline CRP During the Re-Treatment Period Change at Week 24 (n=67)	-15.3 mg/L Standard Deviation 26.62

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population

The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period Week 4	0.8 percentage of participants
Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period Week 12	5.0 percentage of participants
Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period Week 24	5.8 percentage of participants
Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period Week 36	5.8 percentage of participants
Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period Week 48	5.8 percentage of participants

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population

The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score \>3.2 but ≤5.1), or high (DAS28 score \>5.1). A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=77 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Percentage of Participants With Disease Remission According to DAS28 in the Re-Treatment Period Week 12	5.0 percentage of participants
Percentage of Participants With Disease Remission According to DAS28 in the Re-Treatment Period Week 24	4.2 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, and 48 of Initial treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale. The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue. Score changes of 4 points or more were considered clinically meaningful. The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period Change at Week 24 (n=108)	-9.1 scores on a scale Standard Deviation 9.90
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period Baseline (n=120)	28.9 scores on a scale Standard Deviation 10.22
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period Change at Week 4 (n=116)	-5.4 scores on a scale Standard Deviation 8.19
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period Change at Week 12 (n=116)	-7.3 scores on a scale Standard Deviation 10.38
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period Change at Week 36 (n=68)	-8.6 scores on a scale Standard Deviation 11.71
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period Change at Week 48 (n=34)	-10.9 scores on a scale Standard Deviation 10.68

SECONDARY outcome

Timeframe: Weeks 12 and 24 of Re-treatment period

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale. The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue. Score changes of 4 points or more were considered clinically meaningful. The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.

Outcome measures

Outcome measures
Measure	Re-Treatment Period: Rituximab + MTX n=120 Participants Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15. Participants should have been receiving a stable dose (for at least 12 weeks prior to Screening) of MTX 10-25 mg/week and a stable dose of folate (≥5 mg/week) given as either a single weekly dose or as divided daily doses (per investigator discretion). Participants who, in the opinion of the investigator, achieved a clinically relevant response (DAS28 score of ≥2.6) to the first course of treatment received one additional course of re-treatment with rituximab (2 IV infusions of rituximab 1000 mg \[and methylprednisolone 100 mg\] given 14 days apart), at any time between Week 24 and 48.
Change From Baseline in FACIT-F Total Score During the Re-Treatment Period Baseline (n=120)	28.9 scores on a scale Standard Deviation 10.22
Change From Baseline in FACIT-F Total Score During the Re-Treatment Period Change at Week 12 (n=73)	-8.3 scores on a scale Standard Deviation 12.64
Change From Baseline in FACIT-F Total Score During the Re-Treatment Period Change at Week 24 (n=72)	-8.9 scores on a scale Standard Deviation 11.72

Adverse Events

Initial Treatment: Rituximab + MTX

Serious events: 12 serious events

Other events: 102 other events

Deaths: 0 deaths

Re-treatment: Rituximab + MTX

Serious events: 7 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER