The Rheumatic and Musculoskeletal Diseases

B-cells have multiple pathogenic roles in rheumatic and musculoskeletal diseases (RMDs). The two most evaluated strategies for B-cell blockade over the last two decades are B-cell depletion and inhibition of B-cell survival factors (BAFF and/or APRIL). Rituximab, a chimeric monoclonal antibody depletes B-cells by targeting CD20, although the depth, duration of depletion and clinical response may vary between patients.

Recent data have supported the efficacy of reduced rituximab dose and the different retreatment strategies in both its licensed indications; rheumatoid arthritis and granulomatosis with polyangiitis/microscopic polyangiitis, although long-term data are still needed to establish the optimal approach. Despite the failure of rituximab in meeting its primary endpoints when investigated in systemic lupus erythematosus (SLE), primary Sjogren's syndrome and inflammatory myopathies, it may still be used in refractory cases based on clinical efficacy from case series. Mechanistic studies concerning stratification of patients who will respond best to rituximab and personalized therapy are needed but currently limited. Moreover, more data are needed with regards to the use of rituximab biosimilars and the development of humanized and/or Type 2 anti-CD20 agents.

Belimumab, a BAFF-inhibitor, is the only biological therapy that is licensed for SLE in over 50 years. Its action on both B-cells and non-B-cells may have contributed to the success of belimumab trials. However, choosing the right patient for this therapy remains challenging. Long term data, efficacy in other RMDs and better identification of clinical phenotype that will respond to therapy are needed. More data are also needed on the various other strategies for B-cell blockade that are currently under investigation including inhibition of B-cell receptor signaling, development of B-cell tolerogens and targeting plasma cells.
 

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