RT Journal Article
SR Electronic
T1 Balancing Potential Benefits and Risks of Bruton Tyrosine Kinase Inhibitor Therapies in Multiple Sclerosis During the COVID-19 Pandemic
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e1067
DO 10.1212/NXI.0000000000001067
VO 8
IS 6
A1 Martin S. Weber
A1 Jacqueline A. Nicholas
A1 Michael R. Yeaman
YR 2021
UL http://nn.neurology.org/content/8/6/e1067.abstract
AB 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. Here, we 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.BTK=Bruton tyrosine kinase; BTKi=Bruton tyrosine kinase inhibitor; CLL=chronic lymphocytic leukemia; DMT=disease-modifying therapy; Fc=fragment crystallizable; IFN=interferon; IL=interleukin; MS=multiple sclerosis; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; TLR=Toll-like receptor; XLA=X-linked agammaglobulinemia