B Cell-Targeted Therapies in Systemic Lupus Erythematosus

Most high-profile clinical trials of targeted therapies, including those targeting B cells, have failed in systemic lupus erythematosus (SLE). Currently, only one biological therapy has been approved for this condition, belimumab, a monoclonal antibody neutralizing a key B cell survival factor, B cell activating factor of the tumour necrosis factor (TNF) family (BAFF). However, results with this therapeutic are modest and it is not widely used and thus, the search for better therapeutics continue. The reasons for such across the board failure, which has become the norm in SLE clinical trials, as opposed to the numerous therapeutic successes in other autoimmune diseases, appear multifactorial and include a potential combination of suboptimal target selection, patient stratification, use of concomitant immunosuppressive drugs and/or outcome measures as primary endpoint. Lessons can be learned, as much from successful as from failed clinical trials, and clinicians now have a careful focus on optimisation of the study design of future trials via better target identification, patient selection, and use of high-quality outcome measures. In this Chapter, we will review the current status of B cell-targeted therapies in SLE, including targeting strategy achieved via B cell depletion (CD20), through negative regulation of the B cell antigen receptor (BCR) signalling (CD22, Fc gamma receptor (FcγR)IIb), or via neutralizing one or several components of the BAFF/a proliferation-inducing ligand (APRIL) system.