Furie R et al. (2008) Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase 1 trial in patients with systemic lupus erythematosus. Arthritis Res Ther 11: R109

B cells have important pathogenic roles in systemic lupus erythematosus (SLE): they produce autoantibodies, secrete inflammatory cytokines and might promote expansion of autoreactive T cells via antigen presentation. Several treatments that target B cells have, therefore, been investigated in patients with SLE. Furie et al. now report favorable results for their phase I trial of belimumab—a fully human, neutralizing, monoclonal antibody against B-lymphocyte stimulator—which both stimulates proliferation and inhibits apoptosis of B cells.

This multicenter, randomized, double-blind, dose-escalation study of belimumab involved 70 patients with mild-to-moderate SLE, of whom 36 received a single infusion of belimumab (at 1, 4, 10 or 20 mg/kg) or placebo, while the other 34 received two such infusions, 21 days apart. Patients were monitored for 84 days after their last infusion. Belimumab had linear pharmacokinetics across this dose range, and a half-life of approximately 14 days, which suggested that dosing intervals of 28 days were appropriate for future studies. The incidence of adverse events and laboratory abnormalities was similar in treatment and placebo groups. Compared with placebo, belimumab significantly reduced patients' median percentages of CD20+ B cells by up to 47%.

Phase II trials to assess the safety and clinical activity of belimumab in patients with SLE and rheumatoid arthritis are under way.