B-cell depletion therapy in systemic lupus erythematosus: emerging strategies and challenges

INTRODUCTION: B cell plays a pivoting role in the pathogenesis of systemic lupus erythematosus (SLE). In addition to the production of autoantibodies, B cells present antigens to activate the T cells and release proinflammatory cytokines that are relevant for disease activity. B cell modulation remains the spotlight in the development of novel therapeutics in SLE. AREAS COVERED: This article summarizes strategies to enhance B cell depletion in SLE and lupus nephritis (LN). Data on the efficacy of recent clinical trials of B cell depletion in SLE/LN are discussed along with their challenges. EXPERT OPINION: Evidence suggests that deep tissue B cell depletion and delayed repopulation of autoreactive B cells may enhance the durability of response in SLE. Newer generation anti-CD20 biologics, sequential use of anti-CD20 and anti-BAFF, simultaneous inhibition of BAFF and APRIL, as well as the dual action anti-BAFF-R biologic, increase the potency of B cell depletion. However, the major concern of these approaches is the increased risk of infection. Careful selection of SLE patients for B cell modulation therapy and monitoring for infective complications is mandatory while the longer-term results of newer modalities such as the bispecific T cell engagers and chimeric antigen receptor (CAR) therapies are anticipated.