B cell-targeted therapies for systemic lupus erythematosus: an update on clinical trial data

In the past year there has been remarkable activity and some important success in the development of B cell-targeted therapies for the treatment of systemic lupus erythematosus (SLE). The most promising studies were BLISS-52 and BLISS-76, large phase III studies that demonstrated measurable efficacy for belimumab, a monoclonal antibody against B cell-activating factor (BAFF). The moderate-sized phase II/III trials EXPLORER and LUNAR that tested rituximab, an anti-CD20 monoclonal antibody, for treatment of non-renal and renal lupus, disappointed many investigators with anecdotal success in refractory patients. These rituximab trials were intended to detect a large clinical effect in patients with very active disease and this was not found. Nevertheless, arguments can be made for additional studies in targeted populations or with a change in design to detect smaller or longer-term effects. Epratuzumab, a monoclonal antibody against the B cell surface antigen CD22, and atacicept, a chimeric molecule formed by a receptor for BAFF and a proliferation-inducing ligand (APRIL) with immunoglobulin (Ig)-G, have both been promising in initial small trials and now larger clinical trials are underway. Thus, recent clinical trial data show that B cell-targeting therapies are beginning to fulfil their promise as treatments for SLE and there are good reasons to hope for further progress in the near future.