Literature Review (Grey)
Bruton tyrosine kinase inhibitors (BTKis) encompass a new class of therapeutics currently being evaluated for the treatment of multiple sclerosis (MS). Whether BTKis affect COVID-19 risk or severity or reduce vaccine efficacy are important but unanswered questions. In this article the authors provide an overview on BTKi mechanisms relevant to COVID-19 infection and vaccination and review preliminary data on BTKi use in patients with COVID-19. BTKis block B-cell receptor– and myeloid fragment crystallizable receptor–mediated signaling, thereby dampening B-cell activation, antibody class-switching, expansion, and cytokine production. Beyond antibodies, COVID-19 severity and vaccine efficacy appear largely linked to T-cell responses and interferon induction, processes not directly affected by BTKis. Given that B cells have clear roles in antigen presentation to T cells, however, it is possible that BTKis may indirectly interfere with beneficial or detrimental T-cell responses during COVID-19 infection or vaccination. In addition to these possible effects on generating a protective immune response, BTKis may attenuate the hyperinflammatory dysregulation often seen in severe cases of COVID-19 that evolves as a key risk factor in this disease. Currently available outcomes from BTKi-treated patients with COVID-19 are discussed. Clinical trials are currently underway to evaluate the safety and efficacy of BTKis in individuals with MS. Although limited data suggest a potential benefit of BTKis on outcomes for some COVID-19 patients, data from adequately powered, prospective and randomized clinical trials are lacking. Likewise, the specific effect of BTKis on the safety and efficacy of COVID-19 vaccines remains to be determined. Any potential unknown risks that BTKi therapy may present to the patient relative to COVID-19 infection, severity, and vaccine efficacy must be balanced with the importance of timely intervention to prevent or minimize MS progression.
Balancing Potential Benefits and Risks of Bruton Tyrosine Kinase Inhibitor Therapies in Multiple Sclerosis During the COVID-19 Pandemic. Martin S. Weber, Jacqueline A. Nicholas, Michael R. Yeaman. Neurol Neuroimmunol Neuroinflamm Nov 2021, 8 (6) e1067; DOI: 10.1212/NXI.0000000000001067.