Belimumab, a BLyS-specific inhibitor for the treatment of systemic lupus erythematosus

As B cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE), therapies targeting them may provide a valuable treatment for patients with SLE. One of the therapeutic strategies for B-cell targeting is through the inhibition of factors involved in the survival or differentiation of B cells. B-cell-activating factor (BAFF) or B-lymphocyte stimulator (BlyS; trademark of Human Genome Sciences, Rockville, MD, USA) has proven to be a key factor in the selection and survival of B cells. Belimumab is a fully human monoclonal antibody (immunoglobulin G1) that binds to soluble BAFF and inhibits it from binding to its receptors. To date, two phase III trials have demonstrated that belimumab in combination with standard of care significantly reduced SLE disease activity and SLE flare rates in patients with active SLE. In addition, it was generally well tolerated. This article reviews the immune mechanisms induced by the inhibition of BAFF/BLyS and the evidence-based clinical effectiveness of belimumab in SLE patients.