Innate and adaptive immunomodulation by Bruton’s tyrosine kinase (BTK) inhibitors: An emerging treatment for multiple sclerosis

A greater understanding and appreciation regarding the role of B cells in the pathophysiology of multiple sclerosis (MS) has resulted in the successful implementation of B cell-depleting therapies in routine clinical care. As a result of the search for sustainable and effective long-term B cell control, a new mechanism of action that focuses on the inhibition of Bruton’s tyrosine kinase, an enzyme essential for the functioning of B cell receptors (BCRs) and cells of the myeloid lineage, has been proposed. This chapter will explore the current development in multiple BTK inhibitors for treatment of autoimmune diseases, with the main focus on MS. Currently, there are four main BTK inhibitors (evobrutinib, tolebrutinib, fenebrutinib, and BIIB091) that are being investigated in either early- or late-stage MS trials. BTK inhibitors have the potential to provide a better risk-to-benefit ratio in the treatment of MS. However, efficacy and pharmacovigilance data from phase III trials and long-term follow-up are currently lacking and warranted.