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.
Moreover, targeted therapies that are not strictly targeting B-cells, but with a significant effect on them such as the interleukin-6 inhibition are of interest. Alternatively, combination therapy may be effective as evidenced by the treatment for B-cell malignancies. Nevertheless, vigilance is needed from the perspective of safety from prolonged B-cell depletion and thus, long-term safety data are of paramount.
In this Research Topic, our aim is to dissect and improve understanding of the advance in B-cell therapies in various RMDs. This topic is important since B-cell therapies have revolutionized the treatment of patients but more data are needed to refine their use. We are interested in studies concerning biomarkers and stratification of patients to B-cell therapies, treatment strategies, and outcomes as well as efficacy and safety data of the currently available or under investigation. We welcome authors from different subspecialties including rheumatology, immunology, dermatology, nephrology, pulmonary medicine, neurology, and others to contribute their original clinical or experimental research data, review articles or exceptional case reports that shed light on the research theme above with the ultimate goal of improving the care of patients with RMDs.
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.
Moreover, targeted therapies that are not strictly targeting B-cells, but with a significant effect on them such as the interleukin-6 inhibition are of interest. Alternatively, combination therapy may be effective as evidenced by the treatment for B-cell malignancies. Nevertheless, vigilance is needed from the perspective of safety from prolonged B-cell depletion and thus, long-term safety data are of paramount.
In this Research Topic, our aim is to dissect and improve understanding of the advance in B-cell therapies in various RMDs. This topic is important since B-cell therapies have revolutionized the treatment of patients but more data are needed to refine their use. We are interested in studies concerning biomarkers and stratification of patients to B-cell therapies, treatment strategies, and outcomes as well as efficacy and safety data of the currently available or under investigation. We welcome authors from different subspecialties including rheumatology, immunology, dermatology, nephrology, pulmonary medicine, neurology, and others to contribute their original clinical or experimental research data, review articles or exceptional case reports that shed light on the research theme above with the ultimate goal of improving the care of patients with RMDs.