Trial Outcomes & Findings for A Study of Re-Treatment With MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a Single Anti-TNF Inhibitor. (NCT NCT00502840)

Last Updated: 2017-08-18

Results Overview

DAS28 calculated from the swollen joint count (SJC) and tender joint count (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and Patient Global Asessment of disease activity (participant- rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). A clinically meaningful improvement in DAS28 was defined as an improvement of 1.2 units.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

193 participants

Primary outcome timeframe

Week 24

Results posted on

2017-08-18

Participant Flow

Participant milestones

Participant milestones
Measure	Rituximab Plus Methotrexate (MTX) Participants received rituximab 1 gram (g), intravenously (IV), and methylprednisolone 100 mg, IV, on Days 1 and 15 (one cycle). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 milligrams (mg) weekly; participants may also have been receiving a stable dose of folic acid. Participants with Disease Activity Score Based on 28 Joint Count (DAS28) greater than or equal to (≥)2.6 and an improvement in DAS28 greater than (\>0.6) 16 to 24 weeks following treatment could have received up to two additional cycles of rituximab treatment.
Overall Study STARTED	193
Overall Study COMPLETED	93
Overall Study NOT COMPLETED	100

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab Plus Methotrexate (MTX) Participants received rituximab 1 gram (g), intravenously (IV), and methylprednisolone 100 mg, IV, on Days 1 and 15 (one cycle). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 milligrams (mg) weekly; participants may also have been receiving a stable dose of folic acid. Participants with Disease Activity Score Based on 28 Joint Count (DAS28) greater than or equal to (≥)2.6 and an improvement in DAS28 greater than (\>0.6) 16 to 24 weeks following treatment could have received up to two additional cycles of rituximab treatment.
Overall Study Adverse Event	5
Overall Study Additional or changed therapy	48
Overall Study Lack of Efficacy	11
Overall Study Protocol Violation	4
Overall Study Withdrawal by Subject	5
Overall Study Lost to Follow-up	6
Overall Study Administrative problems	1
Overall Study Other	20

Baseline Characteristics

A Study of Re-Treatment With MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a Single Anti-TNF Inhibitor.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab Plus MTX n=193 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one cycle). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional cycles of rituximab treatment.
Age, Continuous	55.5 years n=93 Participants
Sex: Female, Male Female	146 Participants n=93 Participants
Sex: Female, Male Male	47 Participants n=93 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Intent-to-Treat (ITT) Population: all participants who signed the informed consent form, received at least 1 dose of study medication, and where the DAS28 was measured at least once under study medication.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Change From Baseline in DAS28 Score at Week 24	-2.12 scores on a scale Standard Deviation 1.41

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

DAS28 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The DAS28 consists of SJC and TJC measurements, the ESR (measured in mm/hr), and Patient Global Asessment of disease activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
DAS28 Score by Treatment Course and Follow-up (FU) Visit Screening (n=173)	5.15 scores on a scale Standard Deviation 1.09
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 1: FU Week 8 (n=171)	4.09 scores on a scale Standard Deviation 1.22
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 1: FU Week 16 (n=167)	3.72 scores on a scale Standard Deviation 1.29
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 1: FU Week 24 (n=163)	3.78 scores on a scale Standard Deviation 1.25
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 1: FU Month 9 (n=76)	3.94 scores on a scale Standard Deviation 1.56
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 1: FU Month 12 (n=38)	3.79 scores on a scale Standard Deviation 1.38
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 2: FU Week 8 (n=104)	3.69 scores on a scale Standard Deviation 1.25
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 2: FU Week 16 (n=106)	3.34 scores on a scale Standard Deviation 1.04
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 2: FU Week 24 (n=107)	3.56 scores on a scale Standard Deviation 1.26
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 2: FU Month 9 (n=65)	3.53 scores on a scale Standard Deviation 1.34
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 2: FU Month 12 (n=47)	3.98 scores on a scale Standard Deviation 1.50
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 3: FU Week 8 (n=35)	3.59 scores on a scale Standard Deviation 1.09
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 3: FU Week 16 (n=37)	3.25 scores on a scale Standard Deviation 1.07
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 3: FU Week 24 (n=38)	3.65 scores on a scale Standard Deviation 1.39
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 3: FU Month 9 (n=24)	3.94 scores on a scale Standard Deviation 1.33
DAS28 Score by Treatment Course and Follow-up (FU) Visit Course 3: FU Month 12 (n=18)	4.12 scores on a scale Standard Deviation 1.22

SECONDARY outcome

Timeframe: Week 24

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

DAS28 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). 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 had a change from baseline \>1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline \>1.2 with a DAS28 score \>3.2 to ≤5.1 or a change from baseline \>0.6 to ≤1.2 with a DAS28 score ≤5.1.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate' by Treatment Course Course 1 (n=173)	78.0 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate' by Treatment Course Course 2 (n=107)	86.9 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate' by Treatment Course Course 3 (n=38)	86.8 percentage of participants

SECONDARY outcome

Timeframe: Week 24

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

Response was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). 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 had a change from baseline \>1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline \>1.2 with a DAS28 score \>3.2 to ≤5.1 or a change from baseline \>0.6 to ≤1.2 with a DAS28 score ≤5.1; non-responders had a change from baseline ≤0.6 or change from baseline \>0.6 and ≤1.2 with a DAS28 score \> 5.1.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Percentage of Participants Achieving a Response By EULAR Category and Treatment Course Course 2: Moderate response (n=107)	43.9 percentage of participants
Percentage of Participants Achieving a Response By EULAR Category and Treatment Course Course 3: Good response (n=38)	44.7 percentage of participants
Percentage of Participants Achieving a Response By EULAR Category and Treatment Course Course 3: Moderate response (n=38)	42.1 percentage of participants
Percentage of Participants Achieving a Response By EULAR Category and Treatment Course Course 1: Good response (n=173)	32.4 percentage of participants
Percentage of Participants Achieving a Response By EULAR Category and Treatment Course Course 1: Moderate response (n=173)	45.7 percentage of participants
Percentage of Participants Achieving a Response By EULAR Category and Treatment Course Course 2: Good response (n=107)	43.0 percentage of participants

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

HAQ-DI was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The HAQ-DI score consists of questions referring to 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific sub-category items. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The standard disability score was calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered ;total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. The questionnaire was provided in a German translation and was scored based on the instructions from the Stanford University Medical Center.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 1: FU Week 24 (n=164)	1.28 scores on a scale Standard Deviation 0.68
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 1: FU Month 9 (n=76)	1.33 scores on a scale Standard Deviation 0.72
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 1: FU Month 12 (n=39)	1.29 scores on a scale Standard Deviation 0.84
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 2: FU Week 8 (n=100)	1.31 scores on a scale Standard Deviation 0.62
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Screening (n=173)	1.43 scores on a scale Standard Deviation 0.64
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 1: FU Week 8 (n=171)	1.36 scores on a scale Standard Deviation 0.68
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 3: FU Week 24 (n=38)	1.25 scores on a scale Standard Deviation 0.63
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 1: FU Week 16 (n=164)	1.31 scores on a scale Standard Deviation 0.67
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 3: FU Month 9 (n=25)	1.12 scores on a scale Standard Deviation 0.59
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 2: FU Week 16 (n=104)	1.26 scores on a scale Standard Deviation 0.61
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 2: FU Week 24 (n=106)	1.22 scores on a scale Standard Deviation 0.59
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 2: FU Month 9 (n=65)	1.34 scores on a scale Standard Deviation 0.62
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 2: FU Month 12 (n=49)	1.38 scores on a scale Standard Deviation 0.65
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 3: FU Week 8 (n=34)	1.25 scores on a scale Standard Deviation 0.63
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 3: FU Week 16 (n=37)	1.25 scores on a scale Standard Deviation 0.67
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Course 3: FU Month 12 (n=17)	1.35 scores on a scale Standard Deviation 0.57

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

FACIT-F was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The FACIT fatigue scale is based on a 13-item questionnaire to assess the therapy-induced fatigue. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (best) to 52 (worst). The assessment was originally developed for chronic illnesses and is now validated for patients with rheumatoid arthritis (RA). The questionnaire was provided in a German translation.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 3: FU Month 9 (n=24)	17.70 scores on a scale Standard Deviation 12.49
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Screening (n=169)	20.16 scores on a scale Standard Deviation 11.37
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 1: FU Week 8 (n=165)	18.48 scores on a scale Standard Deviation 11.39
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 1: FU Week 16 (n=157)	18.81 scores on a scale Standard Deviation 12.14
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 1: FU Week 24 (n=161)	17.75 scores on a scale Standard Deviation 11.76
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 1: FU Month 9 (n=72)	18.17 scores on a scale Standard Deviation 12.53
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 1: FU Month 12 (n=35)	20.77 scores on a scale Standard Deviation 13.48
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 2: FU Week 8 (n=99)	16.43 scores on a scale Standard Deviation 11.18
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 2: FU Week 16 (n=101)	16.19 scores on a scale Standard Deviation 11.22
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 2: FU Week 24 (n=104)	15.77 scores on a scale Standard Deviation 11.17
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 2: FU Month 9 (n=65)	15.86 scores on a scale Standard Deviation 11.67
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 2: FU Month 12 (n=47)	16.40 scores on a scale Standard Deviation 10.68
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 3: FU Week 8 (n=34)	15.71 scores on a scale Standard Deviation 11.44
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 3: FU Week 16 (n=36)	16.82 scores on a scale Standard Deviation 12.53
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 3: FU Week 24 (n=36)	14.98 scores on a scale Standard Deviation 11.21
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Course 3: FU Month 12 (n=17)	21.40 scores on a scale Standard Deviation 12.74

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and mental composite t-score (MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 1: FU Week 24 (n=161)	37.94 scores on a scale Standard Deviation 8.64
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 3: FU Week 16 (n=35)	39.43 scores on a scale Standard Deviation 8.41
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Screening (n=171)	34.57 scores on a scale Standard Deviation 7.83
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 1: FU Week 8 (n=165)	36.28 scores on a scale Standard Deviation 8.43
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 1: FU Week 16 (n=160)	37.23 scores on a scale Standard Deviation 8.34
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 1: FU Month 9 (n=74)	37.28 scores on a scale Standard Deviation 9.61
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 1: FU Month 12 (n=39)	36.92 scores on a scale Standard Deviation 9.49
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 2: FU Week 8 (n=102)	37.27 scores on a scale Standard Deviation 8.39
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 2: FU Week 16 (n=105)	38.34 scores on a scale Standard Deviation 8.11
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 2: FU Week 24 (n=103)	39.17 scores on a scale Standard Deviation 8.01
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 2: FU Month 9 (n=66)	38.68 scores on a scale Standard Deviation 7.69
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 2: FU Month 12 (n=48)	37.34 scores on a scale Standard Deviation 8.80
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 3: FU Week 8 (n=33)	37.95 scores on a scale Standard Deviation 8.12
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 3: FU Week 24 (n=36)	37.62 scores on a scale Standard Deviation 8.85
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 3: FU Month 9 (n=23)	37.99 scores on a scale Standard Deviation 6.41
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Course 3: FU Month 12 (n=15)	34.95 scores on a scale Standard Deviation 6.32

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
SF-36 MCS by Treatment Course Course 1: FU Month 9 (n=74)	44.35 scores on a scale Standard Deviation 13.38
SF-36 MCS by Treatment Course Screening (n=171)	44.04 scores on a scale Standard Deviation 12.76
SF-36 MCS by Treatment Course Course 1: FU Week 8 (n=165)	45.32 scores on a scale Standard Deviation 12.42
SF-36 MCS by Treatment Course Course 1: FU Week 16 (n=160)	45.06 scores on a scale Standard Deviation 12.06
SF-36 MCS by Treatment Course Course 1: FU Week 24 (n=161)	45.18 scores on a scale Standard Deviation 12.59
SF-36 MCS by Treatment Course Course 1: FU Month 12 (n=39)	41.95 scores on a scale Standard Deviation 14.30
SF-36 MCS by Treatment Course Course 2: FU Week 8 (n=102)	45.94 scores on a scale Standard Deviation 11.34
SF-36 MCS by Treatment Course Course 2: FU Week 16 (n=105)	45.99 scores on a scale Standard Deviation 11.71
SF-36 MCS by Treatment Course Course 2: FU Week 24 (n=103)	46.29 scores on a scale Standard Deviation 11.89
SF-36 MCS by Treatment Course Course 2: FU Month 9 (n=66)	46.93 scores on a scale Standard Deviation 13.56
SF-36 MCS by Treatment Course Course 2: FU Month 12 (n=48)	45.90 scores on a scale Standard Deviation 12.33
SF-36 MCS by Treatment Course Course 3: FU Week 8 (n=33)	46.22 scores on a scale Standard Deviation 10.79
SF-36 MCS by Treatment Course Course 3: FU Week 16 (n=35)	45.52 scores on a scale Standard Deviation 13.41
SF-36 MCS by Treatment Course Course 3: FU Week 24 (n=36)	46.38 scores on a scale Standard Deviation 12.20
SF-36 MCS by Treatment Course Course 3: FU Month 9 (n=23)	44.41 scores on a scale Standard Deviation 13.96
SF-36 MCS by Treatment Course Course 3: FU Month 12 (n=15)	43.67 scores on a scale Standard Deviation 13.73

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 1: FU Week 8 (n=170)	46.80 scores on a scale Standard Deviation 25.20
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 2: FU Month 12 (n=49)	47.41 scores on a scale Standard Deviation 23.62
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 3: FU Week 8 (n=35)	48.01 scores on a scale Standard Deviation 26.63
SF-36 Domain Scores by Treatment Course - Physical Functioning Screening (n=172)	43.26 scores on a scale Standard Deviation 24.74
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 1: FU Week 16 (n=164)	46.85 scores on a scale Standard Deviation 25.16
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 1: FU Week 24 (n=164)	49.58 scores on a scale Standard Deviation 26.45
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 1: FU Month 9 (n=76)	47.30 scores on a scale Standard Deviation 26.17
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 1: Follow-up Month 12 (n=39)	46.92 scores on a scale Standard Deviation 30.21
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 2: FU Week 8 (n=105)	47.17 scores on a scale Standard Deviation 24.51
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 2: FU Week 16 (n=106)	49.03 scores on a scale Standard Deviation 24.91
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 2: FU Week 24 (n=107)	51.10 scores on a scale Standard Deviation 24.23
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 2: FU Month 9 (n=66)	50.50 scores on a scale Standard Deviation 22.87
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 3: FU Week 16 (n=37)	51.35 scores on a scale Standard Deviation 26.84
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 3: FU Week 24 (n=38)	46.32 scores on a scale Standard Deviation 28.44
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 3: FU Month 9 (n=25)	48.23 scores on a scale Standard Deviation 26.16
SF-36 Domain Scores by Treatment Course - Physical Functioning Course 3: FU Month 12 (n=17)	48.99 scores on a scale Standard Deviation 29.37

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
SF-36 Domain Scores by Treatment Course - Bodily Pain Screening (n=172)	37.22 scores on a scale Standard Deviation 18.00
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 1: FU Week 8 (n=169)	46.06 scores on a scale Standard Deviation 20.62
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 1: FU Week 16 (n=164)	47.98 scores on a scale Standard Deviation 22.29
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 1: FU Week 24 (n=164)	48.70 scores on a scale Standard Deviation 21.39
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 1: FU Month 9 (n=75)	46.55 scores on a scale Standard Deviation 25.29
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 1: FU Month 12 (n=39)	44.10 scores on a scale Standard Deviation 25.24
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 2: FU Week 8 (n=105)	47.15 scores on a scale Standard Deviation 20.93
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 2: FU Week 16 (n=106)	50.34 scores on a scale Standard Deviation 21.60
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 2: FU Week 24 (n=104)	51.38 scores on a scale Standard Deviation 22.71
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 2: FU Month 9 (n=66)	51.23 scores on a scale Standard Deviation 20.68
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 2: FU Month 12 (n=48)	48.58 scores on a scale Standard Deviation 24.00
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 3: FU Week 8 (n=35)	47.60 scores on a scale Standard Deviation 18.98
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 3: FU Week 16 (n=36)	51.94 scores on a scale Standard Deviation 18.94
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 3: FU Week 24 (n=38)	47.92 scores on a scale Standard Deviation 21.00
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 3: FU Month 9 (n=25)	43.24 scores on a scale Standard Deviation 19.15
SF-36 Domain Scores by Treatment Course - Bodily Pain Course 3: FU Month 12 (n=16)	32.56 scores on a scale Standard Deviation 18.49

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the physical and mental composite t-scores (PCS and MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Screening (n=173)	45.85 scores on a scale Standard Deviation 23.75
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 1: FU Week 8 (n=170)	50.04 scores on a scale Standard Deviation 24.11
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 1: FU Week 16 (n=166)	51.28 scores on a scale Standard Deviation 24.43
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 1: FU Week 24 (n=165)	52.92 scores on a scale Standard Deviation 24.15
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 1: FU Month 9 (n=76)	49.51 scores on a scale Standard Deviation 25.41
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 1: FU Month 12 (n=39)	47.44 scores on a scale Standard Deviation 25.80
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 2: FU Week 8 (n=103)	52.79 scores on a scale Standard Deviation 24.09
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 2: FU Week 16 (n=106)	53.54 scores on a scale Standard Deviation 21.54
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 2: FU Week 24 (n=107)	55.32 scores on a scale Standard Deviation 23.11
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 2: FU Month 9 (n=66)	56.91 scores on a scale Standard Deviation 20.89
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 2: FU Month 12 (n=49)	52.98 scores on a scale Standard Deviation 20.19
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 3: FU Week 8 (n=35)	52.32 scores on a scale Standard Deviation 21.55
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 3: FU Week 16 (n=36)	53.47 scores on a scale Standard Deviation 25.64
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 3: FU Week 24 (n=38)	50.99 scores on a scale Standard Deviation 23.41
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 3: FU Month 9 (n=24)	51.82 scores on a scale Standard Deviation 23.05
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Course 3: FU Month 12 (n=17)	44.49 scores on a scale Standard Deviation 22.84

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

SF-36was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the physical and mental composite t-scores (PCS and MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Screening (n=173)	57.80 scores on a scale Standard Deviation 27.52
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 1: FU Week 8 (n=170)	61.91 scores on a scale Standard Deviation 26.27
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 1: FU Week 16 (n=166)	60.44 scores on a scale Standard Deviation 28.06
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 1: FU Week 24 (n=165)	62.12 scores on a scale Standard Deviation 26.87
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 1: FU Month 9 (n=76)	56.52 scores on a scale Standard Deviation 28.52
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 1: FU Month 12 (n=39)	55.98 scores on a scale Standard Deviation 30.82
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 2: FU Week 8 (n=104)	61.30 scores on a scale Standard Deviation 25.41
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 2: FU Week 16 (n=106)	62.74 scores on a scale Standard Deviation 25.28
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 2: FU Week 24 (n=107)	61.53 scores on a scale Standard Deviation 25.41
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 2: FU Month 9 (n=66)	62.75 scores on a scale Standard Deviation 26.28
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 2: FU Month 12 (n=49)	61.05 scores on a scale Standard Deviation 23.22
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 3: FU Week 8 (n=34)	60.29 scores on a scale Standard Deviation 25.55
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 3: FU Week 16 (n=37)	61.26 scores on a scale Standard Deviation 29.35
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 3: FU Week 24 (n=38)	60.53 scores on a scale Standard Deviation 26.04
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 3: FU Month 9 (n=24)	54.51 scores on a scale Standard Deviation 31.37
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Course 3: FU Month 12 (n=17)	55.39 scores on a scale Standard Deviation 25.84

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Screening (n=171)	61.71 scores on a scale Standard Deviation 21.25
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 1: FU Week 8 (n=169)	64.38 scores on a scale Standard Deviation 20.36
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 1: FU Week 16 (n=164)	64.70 scores on a scale Standard Deviation 20.02
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 1: FU Week 24 (n=165)	64.26 scores on a scale Standard Deviation 20.77
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 1: FU Month 9 (n=76)	64.08 scores on a scale Standard Deviation 23.23
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 1: FU Month 12 (n=39)	57.85 scores on a scale Standard Deviation 24.50
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 2: FU Week 8 (n=105)	65.44 scores on a scale Standard Deviation 19.45
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 2: FU Week 16 (n=106)	65.33 scores on a scale Standard Deviation 19.75
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 2: FU Week 24 (n=106)	66.45 scores on a scale Standard Deviation 19.63
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 2: FU Month 9 (n=66)	67.67 scores on a scale Standard Deviation 20.60
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 2: FU Month 12 (n=49)	65.82 scores on a scale Standard Deviation 19.75
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 3: FU Week 8 (n=35)	66.43 scores on a scale Standard Deviation 18.01
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 3: FU Week 16 (n=37)	63.99 scores on a scale Standard Deviation 24.25
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 3: FU Week 24 (n=38)	65.46 scores on a scale Standard Deviation 20.87
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 3: FU Month 9 (n=25)	62.80 scores on a scale Standard Deviation 20.82
SF-36 Domain Scores by Treatment Course - Emotional Well-Being Course 3: FU Month 12 (n=16)	61.88 scores on a scale Standard Deviation 21.20

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
SF-36 Domain Scores by Treatment Course - Social Functioning Course 2: FU Week 8 (n=104)	71.27 scores on a scale Standard Deviation 24.44
SF-36 Domain Scores by Treatment Course - Social Functioning Course 2: FU Week 16 (n=106)	71.70 scores on a scale Standard Deviation 24.60
SF-36 Domain Scores by Treatment Course - Social Functioning Course 2: FU Month 9 (n=66)	74.62 scores on a scale Standard Deviation 27.21
SF-36 Domain Scores by Treatment Course - Social Functioning Course 2: FU Month 12 (n=49)	71.68 scores on a scale Standard Deviation 24.84
SF-36 Domain Scores by Treatment Course - Social Functioning Course 3: FU Week 16 (n=37)	66.22 scores on a scale Standard Deviation 25.15
SF-36 Domain Scores by Treatment Course - Social Functioning Course 3: FU Week 24 (n=38)	68.09 scores on a scale Standard Deviation 24.95
SF-36 Domain Scores by Treatment Course - Social Functioning Course 3: FU Month 9 (n=25)	72.50 scores on a scale Standard Deviation 24.74
SF-36 Domain Scores by Treatment Course - Social Functioning Course 3: FU Month 12 (n=17)	66.18 scores on a scale Standard Deviation 32.71
SF-36 Domain Scores by Treatment Course - Social Functioning Screening (n=173)	66.47 scores on a scale Standard Deviation 25.39
SF-36 Domain Scores by Treatment Course - Social Functioning Course 1: FU Week 8 (n=171)	69.01 scores on a scale Standard Deviation 26.55
SF-36 Domain Scores by Treatment Course - Social Functioning Course 1: FU Week 16 (n=166)	68.75 scores on a scale Standard Deviation 25.63
SF-36 Domain Scores by Treatment Course - Social Functioning Course 1: FU Week 24 (n=165)	69.62 scores on a scale Standard Deviation 26.77
SF-36 Domain Scores by Treatment Course - Social Functioning Course 1: FU Month 9 (n=75)	67.50 scores on a scale Standard Deviation 27.34
SF-36 Domain Scores by Treatment Course - Social Functioning Course 1: FU Month 12 (n=39)	66.67 scores on a scale Standard Deviation 30.26
SF-36 Domain Scores by Treatment Course - Social Functioning Course 2: FU Week 24 (n=107)	72.31 scores on a scale Standard Deviation 25.76
SF-36 Domain Scores by Treatment Course - Social Functioning Course 3: FU Week 8 (n=35)	70.00 scores on a scale Standard Deviation 23.13

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
SF-36 Domain Scores by Treatment Course - Vitality Course 1: FU Week 16 (n=164)	50.22 scores on a scale Standard Deviation 20.86
SF-36 Domain Scores by Treatment Course - Vitality Course 1: FU Week 24 (n=165)	50.57 scores on a scale Standard Deviation 21.99
SF-36 Domain Scores by Treatment Course - Vitality Course 1: FU Month 9 (n=76)	50.82 scores on a scale Standard Deviation 22.53
SF-36 Domain Scores by Treatment Course - Vitality Course 1: FU Month 12 (n=39)	45.99 scores on a scale Standard Deviation 22.77
SF-36 Domain Scores by Treatment Course - Vitality Course 2: FU Week 8 (n=105)	50.60 scores on a scale Standard Deviation 20.59
SF-36 Domain Scores by Treatment Course - Vitality Course 2: FU Week 16 (n=106)	52.42 scores on a scale Standard Deviation 20.94
SF-36 Domain Scores by Treatment Course - Vitality Course 2: FU Week 24 (n=106)	54.01 scores on a scale Standard Deviation 21.81
SF-36 Domain Scores by Treatment Course - Vitality Course 2: FU Month 9 (n=66)	55.49 scores on a scale Standard Deviation 19.19
SF-36 Domain Scores by Treatment Course - Vitality Course 2: FU Month 12 (n=49)	52.30 scores on a scale Standard Deviation 18.47
SF-36 Domain Scores by Treatment Course - Vitality Course 3: FU Week 24 (n=38)	52.14 scores on a scale Standard Deviation 24.33
SF-36 Domain Scores by Treatment Course - Vitality Course 3: FU Month 12 (n=16)	42.97 scores on a scale Standard Deviation 23.92
SF-36 Domain Scores by Treatment Course - Vitality Course 3: FU Week 8 (n=35)	53.93 scores on a scale Standard Deviation 24.12
SF-36 Domain Scores by Treatment Course - Vitality Course 3: FU Week 16 (n=37)	51.35 scores on a scale Standard Deviation 24.57
SF-36 Domain Scores by Treatment Course - Vitality Course 3: FU Month 9 (n=25)	52.25 scores on a scale Standard Deviation 26.01
SF-36 Domain Scores by Treatment Course - Vitality Screening (n=172)	46.33 scores on a scale Standard Deviation 20.61
SF-36 Domain Scores by Treatment Course - Vitality Course 1: FU Week 8 (n=169)	49.51 scores on a scale Standard Deviation 21.04

SECONDARY outcome

Timeframe: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

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

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Screening (n=173)	45.74 scores on a scale Standard Deviation 15.72
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 1: FU Week 8 (n=171)	47.46 scores on a scale Standard Deviation 16.56
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 1: FU Week 24 (n=164)	50.65 scores on a scale Standard Deviation 16.91
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 1: FU Month 9 (n=76)	49.38 scores on a scale Standard Deviation 18.15
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 1: FU Month 12 (n=39)	46.15 scores on a scale Standard Deviation 17.85
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 2: FU Week 8 (n=104)	50.32 scores on a scale Standard Deviation 14.43
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 2: FU Week 24 (n=107)	52.93 scores on a scale Standard Deviation 14.92
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 2: FU Month 9 (n=66)	51.04 scores on a scale Standard Deviation 16.95
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 2: FU Month 12 (n=49)	48.98 scores on a scale Standard Deviation 18.60
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 3: FU Week 8 (n=35)	52.27 scores on a scale Standard Deviation 13.09
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 3: FU Week 16 (n=37)	52.14 scores on a scale Standard Deviation 14.07
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 3: FU Week 24 (n=37)	52.90 scores on a scale Standard Deviation 12.31
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 1: FU Week 16 (n=166)	50.82 scores on a scale Standard Deviation 16.23
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 2: FU Week 16 (n=106)	52.04 scores on a scale Standard Deviation 14.78
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 3: FU Month 9 (n=25)	50.54 scores on a scale Standard Deviation 12.96
SF-36 Domain Scores by Treatment Course - General Heath Perceptions Course 3: FU Month 12 (n=17)	45.29 scores on a scale Standard Deviation 14.37

SECONDARY outcome

Timeframe: 24 weeks after each course

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

ACR response was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). ACR20/50/70 response: ≥20/50/70%, respectively, improvement in SJC or TJC and 20/50/70% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Patient's Global Assessment of Disease Activity, 3) Patient's Assessment of Pain, 4) participants assessment of functional disability via HAQ-DI, and 5) C-reactive protein (CRP) or ESR at each visit.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50%, or 70% Improvement (ACR20/ACR50/ACR70) by Treatment Course Course 1: ACR20 (n=173)	38.7 percentage of participants
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50%, or 70% Improvement (ACR20/ACR50/ACR70) by Treatment Course Course 1: ACR70 (n=173)	5.2 percentage of participants
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50%, or 70% Improvement (ACR20/ACR50/ACR70) by Treatment Course Course 2: ACR20 (n=107)	51.4 percentage of participants
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50%, or 70% Improvement (ACR20/ACR50/ACR70) by Treatment Course Course 3: ACR70 (n=38)	7.9 percentage of participants
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50%, or 70% Improvement (ACR20/ACR50/ACR70) by Treatment Course Course 1: ACR50 (n=173)	19.1 percentage of participants
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50%, or 70% Improvement (ACR20/ACR50/ACR70) by Treatment Course Course 2: ACR50 (n=107)	26.2 percentage of participants
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50%, or 70% Improvement (ACR20/ACR50/ACR70) by Treatment Course Course 2: ACR70 (n=107)	5.6 percentage of participants
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50%, or 70% Improvement (ACR20/ACR50/ACR70) by Treatment Course Course 3: ACR20 (n=38)	55.3 percentage of participants
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50%, or 70% Improvement (ACR20/ACR50/ACR70) by Treatment Course Course 3: ACR50 (n=38)	28.9 percentage of participants

SECONDARY outcome

Timeframe: Screening and Week 24

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

Mean sum of 28 swollen joints was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The 28 joints to be assessed for swelling were shoulder, elbow, wrist, metacarpophalangeal (MCP) joints 1-5, proximal interphalangeal (PIP) joints 1-5, and knee on both sides of the body. The sum of swollen joints ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Swollen Joint Count Screening (n=165)	8.52 swollen joints Standard Deviation 5.58
Swollen Joint Count Course 1 FU Week 24 (n=165)	4.09 swollen joints Standard Deviation 5.29
Swollen Joint Count Course 2 FU Week 24 (n=105)	3.65 swollen joints Standard Deviation 4.79
Swollen Joint Count Course 3 FU Week 24 (n=37)	3.51 swollen joints Standard Deviation 5.01

SECONDARY outcome

Timeframe: Screening and Week 24

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

Mean sum of 28 tender joints was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The 28 joints to be assessed for tenderness were shoulder, elbow, wrist, MCP joints 1-5, PIP joints 1-5, and knee on both sides of the body. The sum of tender joints ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Tender Joint Count Screening (n=165)	12.92 tender joints Standard Deviation 9.12
Tender Joint Count Course 1 FU Week 24 (n=165)	7.32 tender joints Standard Deviation 9.60
Tender Joint Count Course 2 FU Week 24 (n=105)	6.31 tender joints Standard Deviation 7.88
Tender Joint Count Course 3 FU Week 24 (n=37)	7.00 tender joints Standard Deviation 9.02

SECONDARY outcome

Timeframe: Baseline and Week 24

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

Physician's Global Assessment of Disease Activity was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). Baseline was defined as the original baseline score from assessment performed in Study ML19070. Physicians were to assess the disease activity on a 100-mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right hand extreme (100 mm) as "maximum disease activity" (maximum arthritis disease activity).

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Physician's Global Assessment of Disease Activity Baseline (n=167)	64.17 mm Standard Deviation 15.12
Physician's Global Assessment of Disease Activity Course 1 Week 24 (n=167)	28.50 mm Standard Deviation 22.23
Physician's Global Assessment of Disease Activity Course 2 Week 24 (n=106)	27.67 mm Standard Deviation 24.32
Physician's Global Assessment of Disease Activity Course 3 Week 24 (n=38)	28.82 mm Standard Deviation 22.52

SECONDARY outcome

Timeframe: Baseline and Week 24

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

Patient Global Assessment of Disease Activity was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). Baseline was defined as the original baseline score from assessment performed in Study ML19070. Participants were to assess the disease activity on a 100-mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right hand extreme (100 mm) as "maximum disease activity" (maximum arthritis disease activity).

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Patient's Global Assessment of Disease Activity Baseline (n=164)	63.40 mm Standard Deviation 21.10
Patient's Global Assessment of Disease Activity Course 1 Week 24 (n=164)	34.13 mm Standard Deviation 23.60
Patient's Global Assessment of Disease Activity Course 2 Week 24 (n=107)	34.50 mm Standard Deviation 23.17
Patient's Global Assessment of Disease Activity Course 3 Week 24 (n=38)	33.66 mm Standard Deviation 23.77

SECONDARY outcome

Timeframe: Baseline and Week 24

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

Patient Assessment of Pain was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). Baseline was defined as the original baseline score from assessment performed in Study ML19070. Participants were to assess their current level of pain on a 100 mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as "no pain" and the right-hand (100 mm) as "unbearable pain".

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Patient's Assessment of Pain Baseline (n=164)	61.90 mm Standard Deviation 21.26
Patient's Assessment of Pain Course 1 Week 24 (n=164)	35.02 mm Standard Deviation 23.50
Patient's Assessment of Pain Course 2 Week 24 (n=107)	35.12 mm Standard Deviation 23.15
Patient's Assessment of Pain Course 3 Week 24 (n=38)	34.82 mm Standard Deviation 25.63

SECONDARY outcome

Timeframe: Baseline and Week 24

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

CRP measured in milligrams per deciliter (mg/dL) was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). Baseline was defined as the original baseline score from assessment performed in Study ML19070.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
C-Reactive Protein Course 1 Week 24 (n=164)	0.89 mg/dL Standard Deviation 1.35
C-Reactive Protein Baseline (n=164)	1.82 mg/dL Standard Deviation 2.41
C-Reactive Protein Course 2 Week 24 (n=105)	0.88 mg/dL Standard Deviation 1.16
C-Reactive Protein Course 3 Week 24 (n=38)	0.84 mg/dL Standard Deviation 0.96

SECONDARY outcome

Timeframe: Baseline and Week 24

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

ESR mean scores measured in mm/hr at was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). Baseline was defined as the original baseline score from assessment performed in Study ML19070.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Erythrocyte Sedimentation Rate Course 1 Week 24 (n=166)	19.87 mm/hr Standard Deviation 14.20
Erythrocyte Sedimentation Rate Baseline (n=166)	31.30 mm/hr Standard Deviation 19.66
Erythrocyte Sedimentation Rate Course 2 Week 24 (n=107)	19.45 mm/hr Standard Deviation 16.42
Erythrocyte Sedimentation Rate Course 3 Week 24 (n=38)	18.74 mm/hr Standard Deviation 11.59

SECONDARY outcome

Timeframe: Baseline and Week 24

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

RF measured in international units per milliliter (IU/mL) was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). Baseline was defined as the original baseline score from assessment performed in Study ML19070.

Outcome measures

Outcome measures
Measure	Rituximab Plus MTX n=173 Participants Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Rheumatoid Factor (RF) Course 3 Week 24 (n=38)	58.52 IU/mL Standard Deviation 117.73
Rheumatoid Factor (RF) Baseline (n=158)	187.18 IU/mL Standard Deviation 339.42
Rheumatoid Factor (RF) Course 1 Week 24 (n=158)	70.16 IU/mL Standard Deviation 163.80
Rheumatoid Factor (RF) Course 2 Week 24 (n=102)	63.17 IU/mL Standard Deviation 144.50

Adverse Events

Rituximab Plus MTX

Serious events: 47 serious events

Other events: 105 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab Plus MTX n=193 participants at risk Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Infections and infestations Gangrene	0.52% 1/193 • 12 months
Infections and infestations Localised infection	0.52% 1/193 • 12 months
Infections and infestations Nasopharyngitis	0.52% 1/193 • 12 months
Infections and infestations Pneumonia	1.0% 2/193 • 12 months
Infections and infestations Respiratory tract infection	1.0% 2/193 • 12 months
Infections and infestations Urinary tract infection	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Femoral neck fracture	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Hip fracture	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Laceration	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Radius fracture	0.52% 1/193 • 12 months
Investigations Hepatic enzyme increased	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Arthritis	1.0% 2/193 • 12 months
Musculoskeletal and connective tissue disorders Back pain	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Bursitis	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.0% 2/193 • 12 months
Musculoskeletal and connective tissue disorders Muscular weakness	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Osteoarthritis	1.0% 2/193 • 12 months
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	2.6% 5/193 • 12 months
Musculoskeletal and connective tissue disorders Rheumatoid nodule	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Synovitis	0.52% 1/193 • 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	1.0% 2/193 • 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.52% 1/193 • 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.52% 1/193 • 12 months
Nervous system disorders Carotid artery stenosis	0.52% 1/193 • 12 months
Nervous system disorders Cerebral infarction	0.52% 1/193 • 12 months
Psychiatric disorders Alcoholism	0.52% 1/193 • 12 months
Reproductive system and breast disorders Genital haemorrhage	0.52% 1/193 • 12 months
Vascular disorders Circulatory collapse	0.52% 1/193 • 12 months
Vascular disorders Femoral artery occlusion	0.52% 1/193 • 12 months
Vascular disorders Hypertension	0.52% 1/193 • 12 months
Vascular disorders Peripheral arterial occlusive disease	0.52% 1/193 • 12 months
Blood and lymphatic system disorders Leukopenia	0.52% 1/193 • 12 months
Blood and lymphatic system disorders Neutropenia	0.52% 1/193 • 12 months
Cardiac disorders Acute myocardial infarction	0.52% 1/193 • 12 months
Cardiac disorders Cardiomegaly	0.52% 1/193 • 12 months
Cardiac disorders Coronary artery disease	1.0% 2/193 • 12 months
Cardiac disorders Coronary artery stenosis	0.52% 1/193 • 12 months
Cardiac disorders Sinus tachycardia	0.52% 1/193 • 12 months
Cardiac disorders Tachyarrhythmia	0.52% 1/193 • 12 months
Endocrine disorders Toxic nodular goitre	0.52% 1/193 • 12 months
Gastrointestinal disorders Gingivitis	0.52% 1/193 • 12 months
Gastrointestinal disorders Inguinal hernia	0.52% 1/193 • 12 months
Gastrointestinal disorders Periodontitis	0.52% 1/193 • 12 months
General disorders Chest pain	0.52% 1/193 • 12 months
Hepatobiliary disorders Cholestasis	0.52% 1/193 • 12 months
Infections and infestations Arthritis bacterial	0.52% 1/193 • 12 months
Infections and infestations Bacterial infection	0.52% 1/193 • 12 months
Infections and infestations Bronchitis	1.0% 2/193 • 12 months
Infections and infestations Chronic sinusitis	0.52% 1/193 • 12 months
Infections and infestations Erysipelas	0.52% 1/193 • 12 months
Infections and infestations Herpes zoster	0.52% 1/193 • 12 months

Other adverse events

Other adverse events
Measure	Rituximab Plus MTX n=193 participants at risk Participants received rituximab 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15 (one course of treatment). Participants should have been receiving mandatory background therapy with MTX (prescribed as necessary by the treating physician) at a stable dose between 7.5 and 25 mg weekly; participants may also have been receiving a stable dose of folic acid. Participants with DAS28 ≥2.6 and an improvement in DAS28 \>0.6 16 to 24 weeks following treatment could have received up to two additional courses of rituximab treatment.
Blood and lymphatic system disorders Anaemia	1.0% 2/193 • 12 months
Blood and lymphatic system disorders Leukopenia	0.52% 1/193 • 12 months
Cardiac disorders Dilatation ventricular	0.52% 1/193 • 12 months
Cardiac disorders Heart valve insufficiency	0.52% 1/193 • 12 months
Ear and labyrinth disorders Tinnitus	0.52% 1/193 • 12 months
Ear and labyrinth disorders Vertigo	1.6% 3/193 • 12 months
Eye disorders Blindness transient	0.52% 1/193 • 12 months
Eye disorders Cataract	0.52% 1/193 • 12 months
Eye disorders Conjunctivitis	1.0% 2/193 • 12 months
Eye disorders Erythema of eyelid	0.52% 1/193 • 12 months
Eye disorders Visual acuity reduced	0.52% 1/193 • 12 months
Gastrointestinal disorders Abdominal pain	1.0% 2/193 • 12 months
Gastrointestinal disorders Abdominal pain upper	1.6% 3/193 • 12 months
Gastrointestinal disorders Diarrhoea	5.7% 11/193 • 12 months
Gastrointestinal disorders Dyspepsia	0.52% 1/193 • 12 months
Gastrointestinal disorders Dysphagia	0.52% 1/193 • 12 months
Gastrointestinal disorders Flatulence	0.52% 1/193 • 12 months
Gastrointestinal disorders Gastritis	2.6% 5/193 • 12 months
Gastrointestinal disorders Glossitis	0.52% 1/193 • 12 months
Gastrointestinal disorders Haemorrhoids	0.52% 1/193 • 12 months
Gastrointestinal disorders Nausea	3.1% 6/193 • 12 months
Gastrointestinal disorders Reflux oesophagitis	0.52% 1/193 • 12 months
Gastrointestinal disorders Stomatitis	0.52% 1/193 • 12 months
Gastrointestinal disorders Vomiting	1.0% 2/193 • 12 months
General disorders Chest pain	0.52% 1/193 • 12 months
General disorders Chills	1.0% 2/193 • 12 months
General disorders Fatigue	2.6% 5/193 • 12 months
General disorders Impaired healing	0.52% 1/193 • 12 months
General disorders Infusion related reaction	3.6% 7/193 • 12 months
General disorders Oedema	0.52% 1/193 • 12 months
General disorders Oedema peripheral	1.0% 2/193 • 12 months
General disorders Pyrexia	0.52% 1/193 • 12 months
Hepatobiliary disorders Cholelithiasis	1.0% 2/193 • 12 months
Immune system disorders Allergy to arthropod sting	0.52% 1/193 • 12 months
Immune system disorders Seasonal allergy	0.52% 1/193 • 12 months
Infections and infestations Acute tonsillitis	1.6% 3/193 • 12 months
Infections and infestations Borrelia infection	0.52% 1/193 • 12 months
Infections and infestations Bronchitis	8.8% 17/193 • 12 months
Infections and infestations Cystitis	1.6% 3/193 • 12 months
Infections and infestations Eye infection bacterial	0.52% 1/193 • 12 months
Infections and infestations Fungal skin infection	0.52% 1/193 • 12 months
Infections and infestations Gastroenteritis	4.1% 8/193 • 12 months
Infections and infestations Gastrointestinal infection	0.52% 1/193 • 12 months
Infections and infestations Herpes ophthalmic	1.0% 2/193 • 12 months
Infections and infestations Herpes simplex	1.0% 2/193 • 12 months
Infections and infestations Herpes virus infection	0.52% 1/193 • 12 months
Infections and infestations Herpes zoster	1.6% 3/193 • 12 months
Infections and infestations Hordeolum	0.52% 1/193 • 12 months
Infections and infestations Infected epidermal cyst	0.52% 1/193 • 12 months
Infections and infestations Influenza	2.1% 4/193 • 12 months
Infections and infestations Laryngitis	0.52% 1/193 • 12 months
Infections and infestations Nasopharyngitis	22.3% 43/193 • 12 months
Infections and infestations Onychomycosis	0.52% 1/193 • 12 months
Infections and infestations Oral candidiasis	0.52% 1/193 • 12 months
Infections and infestations Oral herpes	2.6% 5/193 • 12 months
Infections and infestations Otitis media	1.0% 2/193 • 12 months
Infections and infestations Paronychia	1.0% 2/193 • 12 months
Infections and infestations Pneumonia	0.52% 1/193 • 12 months
Infections and infestations Pyelonephritis	0.52% 1/193 • 12 months
Infections and infestations Respiratory tract infection	4.1% 8/193 • 12 months
Infections and infestations Rhinitis	3.1% 6/193 • 12 months
Infections and infestations Sinusitis	2.6% 5/193 • 12 months
Infections and infestations Tinea pedis	1.6% 3/193 • 12 months
Infections and infestations Tonsillitis	0.52% 1/193 • 12 months
Infections and infestations Tooth infection	1.0% 2/193 • 12 months
Infections and infestations Upper respiratory tract infection	6.2% 12/193 • 12 months
Infections and infestations Urinary tract infection	1.6% 3/193 • 12 months
Infections and infestations Vaginal infection	0.52% 1/193 • 12 months
Infections and infestations Viral infection	1.0% 2/193 • 12 months
Infections and infestations Vulvovaginal mycotic infection	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Animal bite	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Arthropod bite	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Arthropod sting	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Contusion	2.1% 4/193 • 12 months
Injury, poisoning and procedural complications Epicondylitis	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Fall	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Hand fracture	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Rib fracture	1.0% 2/193 • 12 months
Injury, poisoning and procedural complications Tendon rupture	1.0% 2/193 • 12 months
Injury, poisoning and procedural complications Thermal burn	0.52% 1/193 • 12 months
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.52% 1/193 • 12 months
Investigations Blood creatinine increased	0.52% 1/193 • 12 months
Investigations Body temperature increased	0.52% 1/193 • 12 months
Investigations Hepatic enzyme increased	0.52% 1/193 • 12 months
Metabolism and nutrition disorders Anorexia	0.52% 1/193 • 12 months
Metabolism and nutrition disorders Diabetes mellitus	1.0% 2/193 • 12 months
Metabolism and nutrition disorders Hypercholesterolaemia	0.52% 1/193 • 12 months
Metabolism and nutrition disorders Hyperlipidaemia	1.0% 2/193 • 12 months
Metabolism and nutrition disorders Hyperuricaemia	0.52% 1/193 • 12 months
Metabolism and nutrition disorders Iron deficiency	0.52% 1/193 • 12 months
Metabolism and nutrition disorders Vitamin D deficiency	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Arthralgia	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Arthritis	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Back pain	3.1% 6/193 • 12 months
Musculoskeletal and connective tissue disorders Bursitis	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Dactylitis	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Jaw cyst	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Joint effusion	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Joint lock	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Muscular weakness	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.0% 2/193 • 12 months
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Myalgia	1.0% 2/193 • 12 months
Musculoskeletal and connective tissue disorders Neck pain	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Osteoarthritis	1.6% 3/193 • 12 months
Musculoskeletal and connective tissue disorders Osteopenia	1.0% 2/193 • 12 months
Musculoskeletal and connective tissue disorders Osteoporosis	1.0% 2/193 • 12 months
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Rheumatoid nodule	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	1.0% 2/193 • 12 months
Musculoskeletal and connective tissue disorders Synovitis	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.52% 1/193 • 12 months
Musculoskeletal and connective tissue disorders Tendonitis	0.52% 1/193 • 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.52% 1/193 • 12 months
Nervous system disorders Carpal tunnel syndrome	1.0% 2/193 • 12 months
Nervous system disorders Dizziness	0.52% 1/193 • 12 months
Nervous system disorders Dysaesthesia	1.0% 2/193 • 12 months
Nervous system disorders Headache	2.6% 5/193 • 12 months
Nervous system disorders Migraine	0.52% 1/193 • 12 months
Nervous system disorders Neurological symptom	0.52% 1/193 • 12 months
Nervous system disorders Paraesthesia	0.52% 1/193 • 12 months
Nervous system disorders Polyneuropathy	1.0% 2/193 • 12 months
Nervous system disorders Sciatica	1.0% 2/193 • 12 months
Psychiatric disorders Depressed mood	0.52% 1/193 • 12 months
Psychiatric disorders Depression	3.1% 6/193 • 12 months
Psychiatric disorders Depressive symptom	0.52% 1/193 • 12 months
Psychiatric disorders Insomnia	1.6% 3/193 • 12 months
Psychiatric disorders Psychotic disorder	0.52% 1/193 • 12 months
Psychiatric disorders Sleep disorder	0.52% 1/193 • 12 months
Psychiatric disorders Transient psychosis	0.52% 1/193 • 12 months
Renal and urinary disorders Nephrolithiasis	1.0% 2/193 • 12 months
Renal and urinary disorders Renal failure	0.52% 1/193 • 12 months
Renal and urinary disorders Urethral stenosis	0.52% 1/193 • 12 months
Reproductive system and breast disorders Gynaecomastia	1.0% 2/193 • 12 months
Reproductive system and breast disorders Menopausal symptoms	0.52% 1/193 • 12 months
Respiratory, thoracic and mediastinal disorders Asthma	0.52% 1/193 • 12 months
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.52% 1/193 • 12 months
Respiratory, thoracic and mediastinal disorders Cough	4.1% 8/193 • 12 months
Respiratory, thoracic and mediastinal disorders Dysphonia	1.0% 2/193 • 12 months
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	1.0% 2/193 • 12 months
Respiratory, thoracic and mediastinal disorders Epistaxis	2.1% 4/193 • 12 months
Respiratory, thoracic and mediastinal disorders Lung disorder	0.52% 1/193 • 12 months
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.52% 1/193 • 12 months
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	1.0% 2/193 • 12 months
Respiratory, thoracic and mediastinal disorders Throat tightness	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Acrodermatitis	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Decubitus ulcer	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Dermatitis allergic	1.6% 3/193 • 12 months
Skin and subcutaneous tissue disorders Drug eruption	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Eczema	1.6% 3/193 • 12 months
Skin and subcutaneous tissue disorders Erythema	1.0% 2/193 • 12 months
Skin and subcutaneous tissue disorders Hyperhidrosis	1.6% 3/193 • 12 months
Skin and subcutaneous tissue disorders Nail bed inflammation	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Night sweats	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Panniculitis	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Pruritus	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Rash	2.6% 5/193 • 12 months
Skin and subcutaneous tissue disorders Rash papular	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Rosacea	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Skin lesion	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Skin ulcer	1.0% 2/193 • 12 months
Skin and subcutaneous tissue disorders Urticaria	0.52% 1/193 • 12 months
Skin and subcutaneous tissue disorders Urticaria localised	0.52% 1/193 • 12 months
Vascular disorders Hot flush	1.0% 2/193 • 12 months
Vascular disorders Hypertension	3.6% 7/193 • 12 months
Vascular disorders Hypertensive crisis	1.0% 2/193 • 12 months
Vascular disorders Peripheral arterial occlusive disease	0.52% 1/193 • 12 months
Vascular disorders Thrombosis	0.52% 1/193 • 12 months
Eye disorders Eyelid oedema	0.52% 1/193 • 12 months

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