Phase 3 data show benefit from RA drug combination in methotrexate nonresponders

Incidences of overall and serious adverse events were comparable between rituximab- and placebo-treated groups.

A phase 3 clinical study evaluating rituximab plus methotrexate for treating rheumatoid arthritis found that the drug combination significantly improved patients' American College of Rheumatology-20 scores at 24 weeks follow-up compared patients treated with placebo plus methotrexate, according to a press release from Genentech Inc. and Biogen Idec, which co-market the drug in the United States.

The study, called SERENE, involved patients with moderately-to-severely active rheumatoid arthritis (RA) who inadequately responded to prior methotrexate monotherapy. Investigators enrolled a total of 509 patients at 102 study sites in 11 countries.

These patients were randomly assigned to one of two Rituxan (rituximab) treatment groups, or the placebo group. Patients assigned to the rituximab treatment groups received a two-infusion course of either 500-mg or 1,000-mg of the drug combined with a stable dose of methotrexate.

Although the study was not designed to compare rituximab doses, treatment efficacy appeared to be similar between both rituximab doses, according to the release.

"While use of [rituximab] with methotrexate is well-established in RA patients who have had an inadequate response to anti-TNF therapy, this is the first phase 3 study demonstrating that [rituximab] improved symptoms of RA in patients who had not previously been treated with a biologic therapy," Hal Barron, MD, Genentech's senior vice president of development and chief medical officer, stated in the release. "These findings support the potential use of [rituximab] earlier in the course of treatment."

"These data provide further support for B-cell therapy in RA," Evan Beckman, MD, Biogen Idec's senior vice president of immunology research and development, noted in the release. "We look forward to sharing the full analysis results from SERENE with the medical community and the FDA."

A preliminary data analysis found no unexpected safety signals, according to the release.

The incidence of overall adverse events and serious adverse events were comparable between rituximab- and placebo-treated groups. The overall rates of infections and serious infections were also comparable between treatment groups.

Patients treated with rituximab showed a higher rate of infusion-related reactions from the first rituximab infusion. However, the reactions were primarily mild to moderate in severity and reversible with medical intervention, the release stated.

There were no serious infusion reactions with rituximab, and the companies continue to monitor its the long-term safety, the release noted.

Genentech and Biogen Idec co-market Rituxan in the United States, and Roche markets the drug under the trade name MabTheraRA to all other markets, except Japan where it is co-marketed by Chugai and Zenyaku Kogyo Co. Ltd.