A Study of the Safety and Efficacy of Rituximab in Patients With Moderate to Severe Rheumatoid Arthritis Receiving Methotrexate (RUMBA)

Rituximab: 1000 mg intravenous (IV) on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18).

Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion.

Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant).

Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).

Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12.) For the Month 6 and 18 cycles, rituximab or placebo was administered.

Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion.

Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant).

Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).

A Grade III Adverse Event (AE) is severe; defined as considerable interference with the subject's daily activities, medical intervention/therapy required and hospitalization possible.

A Grade IV AE is life-threatening; defined as extreme limitation in activity, significant medical intervention/therapy required, hospitalization probable.

Because of the small sample size and the small number of subjects who completed Week 104, the analysis were limited to descriptive statistics only.

ACR20 response was defined as satisfying the following 3 criteria improvement from baseline: ≥ 20% in tender joint count; ≥ 20% in swollen joint count; ≥ 20% improvement from baseline in 3 of the following 5 criteria:

Subject's Global Assessment of Pain Subject's Global Assessment of Disease Activity Physician's Global Assessment Subject's Self-Assessment Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) Note: The definitions of ACR50 and ACR70 are the same as ACR20, except that the 20% value in the above definition is replaced by 50% and 70% values, respectively.

Major clinical response is an ACR70 response defined as improvement from baseline: ≥70% in tender joint count; ≥70% in swollen joint count; ≥70% in 3 of the following: Patient Pain Assessment, Patient Global Assessment, Physician Global Assessment, Patient Self-Assessed Disability, ESR or CRP for ≥169 consecutive days.

Remission: ≥5 requirements fulfilled for ≥2 consecutive months: Duration of morning stiffness <15 minutes, No fatigue, No joint pain, No joint tenderness or pain on motion, No soft tissue swelling in joints or tendon sheaths, ESR <30 mm/hour for women and <20 mm/hour for men.

EULAR remission = DAS28-4(CRP) < 2.6 (Fransen et al. 2004.

EULAR response categories (van Gestel et al. 1999):

Good response = final DAS28-4(CRP) < 3.2 and decreased > 1.2 points from baseline Moderate response = final DAS28-4(CRP) ≥ 3.2 but ≤ 5.1 and decreased > 0.6 points from baseline or final DAS28-4(CRP) > 5.1 and decreased > 1.2 from baseline.