Genentech, Inc. (SOUTH SAN FRANCISCO, California) and Biogen Idec, Inc. (Cambridge, Massachusetts) announced Rituxan^® (rituximab) data, including results from phase II and III studies of Rituxan in patients with moderately-to-severely active rheumatoid arthritis (RA). Among the studies reported were a phase III controlled retreatment trial with Rituxan in patients who have had an inadequate response to previous treatment with one or more TNF antagonist therapies; data from the first phase III study of Rituxan plus methotrexate (MTX) in biologic-naïve RA patients; and phase II data evaluating immune response to vaccines in Rituxan-treated patients.

Data from SUNRISE, the first randomized, double-blind, placebo-controlled phase III study assessing fixed interval re-treatment of Rituxan in moderately-to-severely active RA patients who had an inadequate response to previous treatment with at least one TNF inhibitor, demonstrated that at 48 weeks, a significantly greater proportion of patients who received two courses of Rituxan (two infusions of 1000 mg at each course) maintained an ACR20 response compared to those who received one course of Rituxan followed by one course of placebo. Of the 318 patients retreated with a second course of Rituxan, 53.5% achieved an ACR20 response compared to 44.6% of the 157 patients who received one course of Rituxan and were retreated with placebo (P = .0195). Patients who achieved clinical response to a first course of Rituxan and received retreatment with placebo were more likely to lose response, compared to patients who received retreatment with Rituxan. The incidence of adverse events (AEs), serious adverse events (SAEs) or infections among patients receiving one or two courses of Rituxan was similar.

Data from a 24-week pivotal phase III study known as SERENE evaluating Rituxan in 509 biologic-naïve RA patients who inadequately responded to MTX demonstrated a statistically significant improvement in ACR20 scores among patients who received a single treatment course of two infusions of either 500 mg or 1000 mg of Rituxan in combination with a stable dose of MTX compared with patients who received placebo in combination with MTX (55.1% and 50.6% for the Rituxan treatment arms compared to 23.3% in the placebo arm, P<.0001 for both comparisons), achieving the primary endpoint. The incidence of overall AEs, SAEs, overall infections, and serious infections was comparable between Rituxan and placebo treatment groups in SERENE. Although there were more infusion-related reactions with the first Rituxan infusion, these reactions were primarily mild-to-moderate in severity and reversible with medical intervention. There were no serious infusion reactions with Rituxan.

A phase II study known as SIERRA showed comparable immune response to tetanus vaccines in patients receiving Rituxan in combination with MTX compared with patients receiving placebo plus MTX (39% of Rituxan-treated patients with a 4-fold titer rise compared with 42% of patients receiving placebo). Patients who received Rituxan in combination with MTX had decreased responses to pneumococcal polysacchride vaccine. However, many patients were able to mount responses (57% of Rituxan-treated patients with a 2-fold titer rise to greater than or equal to 1 pneumococcal serotype compared with 82% of patients receiving placebo).

Rituxan, in combination with MTX, is indicated to reduce signs and symptoms and to slow the progression of structural damage in adult patients with moderately-to-severely active RA who have had an inadequate response to one or more TNF antagonist therapies. Genentech and Biogen Idec submitted a supplemental Biologics License Application (sBLA) on September 15, 2008, for an expanded indication for Rituxan in patients with moderately-to-severely active RA who inadequately respond to one or more nonbiologic DMARD(s).