BTK inhibitors in multiple sclerosis: emerging evidence and future directions

Introduction: Available disease modifying treatments (DMTs) for multiple sclerosis (MS) impact on the immune adaptive response without inhibiting innate immune cells that participate in disease progression. Bruton tyrosine kinase (BTK) inhibitors are an emerging treatment being intensely evaluated in MS. This review highlights the potential use of BTK inhibitors in the treatment of MS by exploring mechanisms of action, recent clinical findings, and gaps in implementation. Areas covered: This narrative review traces the roots of the use of BTK inhibitors for the treatment of MS. PubMed, EMBASE, Scopus and Google Scholar were searched for publications using combinations of terms related to ‘multiple sclerosis,’ ‘Bruton Tirosin Kinase inhibitors,’ ‘chronic inflammation,’ ‘disability progression.’ Official websites were also screened. Expert opinion: BTK inhibitors can cross the blood-brain barrier (BBB) and have the potential to impact on processes of compartmentalized chronic neuroinflammation within the central nervous system, which promote MS progression. There is growing evidence that BTK inhibitors may play a role in preventing disability in MS, mainly in patients with progressive disease, with limited anti-inflammatory activity. Although BTK inhibitors appear highly promising, several questions remain unanswered and their positioning within the therapeutic landscape of MS is still yet to be fully clarified.