A Study of MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Therapies.

ACR20 response: ≥20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; Patient Global Assessment of Disease Activity (PtGA); Physician Global Assessment of Disease Activity (PGA); self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ-DI\]); and either C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR).

Time frame: Week 24

Population: ITT population

The mean level of CRP in milligrams per liter (mg/L), an acute phase reactant, at Week 0 and the change from Week 0 to Weeks 24 and 48.

Time frame: Baseline, Weeks 24 and 48

Population: ITT population

DAS28 was calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (millimeters per hour \[mm/hr\]) and PtGA of disease activity with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 ≤3.2 equals (=) low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity.

Time frame: Baseline and Week 24

Population: ITT population

The mean level of ESR (in mm/hr), an acute phase reactant, at Week 0 and the change from Week 0 to Weeks 24 and 48.

Time frame: Baseline, Weeks 24 and 48

Population: ITT population

HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Time frame: Baseline, Weeks 24 and 48

Population: ITT population

Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Maximum total erosion score in the hands was 100 and in the feet was 42, for a maximum overall score of 142. Total erosion score was for both hands and feet.

Time frame: Screening, Weeks 24 and 48

Population: ITT population

JSN Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). Maximum total scores for JSN in the hands was 100 and in the feet was 48, for a maximum overall score of 148. Total JSN was for both hands and feet.

Time frame: Screening, Weeks 24 and 48

Population: ITT population. 39 participants were analyzed for this outcome measure.

Posterior-anterior (PA) radiograph of each hand and anterior-posterior (AP) radiograph of each foot were taken separately and assessed according to Genant's method as modified from Sharp's method. The Sharp-Genant score=total of the erosion score and the joint space narrowing (JSN) score of all the hands and feet. Erosion Score: 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. JSN Score:13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). Maximum total erosion score in hands=100 and in feet=42; maximum scores for JSN in the hands=100 and in feet=48. Maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score. Change in scores was calculated as change=final score minus initial score.

Time frame: Screening and Weeks 24 and 48

Population: ITT population

The mean score of pain at Week 0 (baseline) and the change from Week 0 to Weeks 24 and 48 as assessed by participants using a 100-mm horizontal VAS, where the left endpoint indicated No pain, and the right endpoint indicated Unbearable pain. A negative change indicated improvement.

Time frame: Baseline, Weeks 24 and 48

Population: ITT population

The mean score of the symptoms of rheumatoid arthritis (RA) at Week 0 (baseline) and the change from Week 0 to Weeks 24 and 48 as assessed by participants using a 100 mm horizontal VAS, where the left endpoint indicated No disease activity (no symptom, or no symptom of RA), and the right endpoint indicated Maximum disease activity (maximum RA activity). A negative change from Baseline indicated improvement.

Time frame: Baseline, Weeks 24 and 48

Population: ITT population

ACR50 response: ≥50% improvement in tender joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; PtGA; PGA; self-assessed disability (HAQ-DI); and either CRP or ESR.

Time frame: Week 24

Population: ITT population

ACR70 response: ≥70% improvement in tender joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; PtGA; PGA; self-assessed disability (HAQ-DI); and either CRP or ESR.

Time frame: Week 24

Population: ITT population

DAS28 was calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and PtGA of disease activity with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity.

Time frame: Baseline, Week 24

Population: ITT population

The percentage of participants categorized as good, moderate, or nonresponders according to the EULAR response criteria at Week 24. Participants were categorized as good responders if the intensity of their symptoms was in the low disease activity (DAS28 less than \[\<\]3.2) category after treatment, and their symptoms significantly decreased to \>1.2. Participants were categorized as moderate responders if the intensity of their symptoms was in the moderate or high disease activity (DAS28 \>3.2) category after treatment, and the symptoms significantly decreased to \>1.2; or if the intensity of their symptoms was in the low or moderate disease activity (DAS28 \<5.1) category, and the DAS28 score changed more than 0.6 or 1.2 or less. Participants were categorized as non-responders if they did not fall into the good or moderate categories.

Time frame: Week 24

Population: ITT population

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

Time frame: Screening, Weeks 24 and 48

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

The mean score of the symptoms of RA at Week 0 and the change from Week 0 (baseline) to Weeks 24 and 48 as assessed by investigators using a 100-mm horizontal VAS, where the left endpoint indicated No disease activity (no symptom, or no symptom of RA), and the right endpoint indicated Maximum disease activity (maximum RA activity). A negative change from Baseline indicated improvement.

Time frame: Baseline, Weeks 24 and 48

Population: ITT population

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

Time frame: Screening, Weeks 24 and 48

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

Number of swollen joints was determined by examination of 66 joints (as assessed through pressing and palpating during the physical examination) and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit as swollen or not swollen.

Time frame: Baseline, Weeks 24 and 48

Population: ITT population

Number of tender joints was determined by examination of 68 joints (as assessed through pressing and palpating during the physical examination) and identifying when swelling was present. The number of tender joints was recorded on the joint assessment form at each visit as either tender or not tender.

Time frame: Baseline, Weeks 24 and 48

Population: ITT population