Evolution and trajectory of B-cell targeted therapies in rheumatic diseases.

Aberrant B-cell function, which could arise from various underlying causes, is central to the pathogenesis of diverse autoimmune rheumatic diseases. B cells remain the only cell type to be specifically therapeutically targeted through depletion and have the only therapy with a routinely available flow cytometric biomarker of treatment. Since first use and subsequent licensing for rheumatoid arthritis, rituximab has had a transformative impact on patients globally and across the rheumatic diseases. Further insights from B-cell-activating factor (BAFF) blockade with belimumab in systemic lupus erythematosus have followed. Examination of B-cell depletion, clinical outcomes, and re-emergent disease after treatment have deepened our understanding of the identity, detailed phenotype, biology, and kinetics of the B-cell subsets that are central to disease. This Review reflects on 20 years of clinical and translational insights drawn from B-cell targeted therapies for adult autoimmune rheumatic diseases, and highlights how these therapies have informed an exciting new era of future therapeutic developments.