Targeting B cells in multiple sclerosis

Abstract

Purpose of review Treatments targeting B cells are increasingly used for patients with multiple sclerosis (MS). We review the mechanisms of action, clinical effectiveness and safety of treatment, with emphasis on recently published studies. Recent findings Several monoclonal antibodies targeting the surface molecule CD20 on B cells are approved or being developed for treatment of MS. Overall, they seem comparable in terms of strongly suppressing radiological disease activity and relapse biology. Novel approaches include anti-CD19 antibody therapy and treatment with oral drugs targeting Bruton's tyrosine kinase (BTK). The main safety issue with persistent B cell depletion is an increased risk of infections – possibly including an increased risk of severe COVID-19. Vaccine responses are also blunted in patients treated with anti-CD20 antibodies. Lower doses or longer infusion intervals may be sufficient for control of disease activity. Whether this might also improve the safety of treatment and increase vaccination responses remains to be determined. Summary Available data support the widespread use of therapies targeting B cells in MS. Whether novel approaches targeting CD19 or BTK will have advantages compared to anti-CD20 antibody therapy remains to be established. Furthermore, trials investigating alternative dosing regimens for anti-CD20 antibody treatment are warranted.

Leptomeningeal enhancement in multiple sclerosis and other neurological diseases: A systematic review and Meta-Analysis

“…However, most of these studies have a small sample size and might thus be insufficiently powered to detect a potential therapeutic effect. In addition, newer DMTs such as Bruton tyrosine kinase inhibitors ( Sellebjerg and Weber, 2021 ) have not been assessed in this regard, even though these drugs led to a resolution of LME in one rodent study employing a neuroinflammatory model ( Bhargava et al, 2021 ). Hence, more data is needed on potential therapeutic impact of DMT on LME resolution.…”

Radiosynthesis of [11C]Ibrutinib via Pd-Mediated [11C]CO Carbonylation: Preliminary PET Imaging in Experimental Autoimmune Encephalomyelitis Mice

“…Bruton's tyrosine kinase (BTK) is critical for the maturation of B cells and in regulating hematopoietic cell circulation (1,2). BTK inhibitors have been developed to treat B-cell malignancies and autoimmune diseases including multiple sclerosis (MS) (3,4), where it is postulated that inhibiting BTK blocks the maturation of B cells (5)(6)(7)(8)(9). Ibrutinib is a first-generation BTK inhibitor used as a chemotherapeutic agent to treat B-cell cancers (10).…”

Leptomeningeal Enhancement in Multiple Sclerosis and Other Neurological Diseases: A Systematic Review and Meta-Analysis

“…However, most of these studies have a small sample size and might thus be insufficiently powered to detect a potential therapeutic effect. In addition, newer DMTs such as Bruton tyrosine kinase inhibitors (59) have not been assessed in this regard, even though these drugs led to a resolution of LME in one rodent study employing a neuroinflammatory model. (36).…”