B cell-targeted therapies in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology that primarily affects women of childbearing age. There is no disease more heterogeneous than SLE as patients experience a myriad of manifestations and unpredictable periods of heightened disease activity. This heterogeneity not only makes it difficult for treatment decisions and prognostication, but has made drug development quite challenging. Despite these challenges, belimumab, voclosporin, and anifromulab, approved by the United States Food and Drug Administration (FDA) to treat SLE or lupus nephritis (LN), enhanced our armamentarium of traditional therapies, such as hydroxychloroquine, corticosteroids, and immunosuppressives. However, there remains a dire need to develop therapies that offer greater efficacy and safety. Patients with SLE produce excessive amounts of autoantibodies and cytokines that result in inflammation and organ damage. While a considerable number of potential drug development targets exist, there has been much attention focused on B cells. Strategies have included direct B cell killing, modulation of B cell function, inhibition of molecules essential to B cell growth and survival, and acceleration of autoantibody clearance, to name just a few. In this article, we review SLE clinical trials evaluating experimental agents that target B cells or plasma cells.