CHICAGO — A host of promising new therapies for rheumatoid arthritis are in development, including the human monoclonal antibody belimumab, Mark C. Genovese, M.D., reported at a symposium sponsored by the American College of Rheumatology.
Belimumab inhibits the activity of B-lymphocyte stimulator (BLyS), a protein that is elevated in the blood and joint fluid of people who have rheumatoid arthritis (RA).
BLyS is believed to contribute to the production of autoantibodies, especially rheumatoid factor, which appears to correlate with disease severity.
An interim analysis of a phase II trial of belimumab (LymphoStat-B) showed a clinical effect at various doses in 283 patients with active moderate to severe RA, said Dr. Genovese, an investigator for Human Genome Sciences, which sponsored the study.
Belimumab also produced statistically significant reductions in all active treatment groups of circulating B cells (CD 20+ and other subsets) and rheumatoid factor, compared with placebo.
“It's an encouraging therapy,” Dr. Genovese told this newspaper. “But that enthusiasm has to be tempered by the fact we have to see more studies.”
Patients were allowed concurrent standard-of-care therapy, including at least one TNF-α inhibitor and up to 10 mg/day of prednisone.
About 73% of patients were receiving background methotrexate. More than one-third of patients (38%) had been failed by at least one TNF-α inhibitor.
Patients were randomized to receive placebo or belimumab in doses of 1 mg/kg, 4 mg/kg, or 10 mg/kg, given intravenously for 24 weeks.
All patients were dosed on days 0, 14, and 28, then every 28 days for the remainder of the 24 weeks.
The study's primary efficacy end point was the achievement of an American College of Rheumatology (ACR) 20 response at 24 weeks.
Among those in the 1-mg/kg group, 36% achieved an ACR 20 response, as did 17% in the placebo group. This between-group difference was statistically significant.
Trends toward a drug benefit were seen in the 4-mg/kg group (28% ACR 20) and in the 10-mg/kg group (29% ACR 20).
Adverse events were similar across treatment groups, and clinically significant infusion reactions were rare, according to a statement by Human Genome Sciences.
Another promising therapy, rituximab, is a monoclonal antibody that targets CD20 on B cells, said Dr. Genovese, chief of clinical services in the division of immunology and rheumatology at Stanford University, Palo Alto, Calif.
A preliminary analysis of phase III data from the Randomized Evaluation of Long-term Efficacy of Rituximab in RA (REFLEX) trial showed that a greater proportion of rituximab-treated patients achieved an ACR 20 at week 24 than those taking placebo, said Dr. Genovese, also a consultant for Genentech Inc., which sponsored the study.
The study included patients with active RA who had an inadequate response or were intolerant to prior treatment with one or more anti-TNF therapies.
The data did not show anything unexpected regarding safety or efficacy, said Stanley B. Cohen, M.D., the principal investigator for the Radiant Research site of the trial.
The findings so far support the hypothesis that “we have a potential therapy that we can use in patients with disease that is refractory to our most potent therapies to date, which are TNF inhibitors,” Dr. Cohen said in an interview.
Detailed results from REFLEX are expected to be presented at the annual congress of the European League Against Rheumatism in June.