Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR).

Objective: To evaluate the efficacy and safety of three dosing and repeat treatment regimens of rituximab (RTX) plus MTX in patients with active RA.

Methods: Patients with active RA despite stable MTX (10-25 mg/week) were randomly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart: 2 x 500 and 2 x 500 mg; 2 x 500 and 2 x 1000 mg (dose escalation); and 2 x 1000 and 2 x 1000 mg. The primary endpoint was proportion of patients achieving ACR20 at Week 48.

Rituximab pharmacokinetics in patients with rheumatoid arthritis: B-cell levels do not correlate with clinical response.

This study characterized the relationship between clinical response, serum rituximab concentrations, and peripheral B-cell levels in patients with rheumatoid arthritis treated with rituximab. Data were analyzed from a double-blind, phase IIa trial in which 161 patients with active rheumatoid arthritis despite continuing methotrexate were randomized to methotrexate alone (10-25 mg/wk), rituximab alone (single course: 1000 mg administered intravenously on days 1 and 15), rituximab plus cyclophosphamide (750 mg administered intravenously on days 3 and 17), or rituximab plus methotrexate. Serum samples for pharmacokinetic analysis were collected through 24 weeks, and peripheral circulating CD19+ B-cell levels were measured through 48 weeks.