Hasan Ibrahim MATAR, Mohammad Nabeel BANIAMER, Abdullah I. ALSARAYRAH, Aya Abd-elsalam AL-RJOUB, Ammar Samer ALTAWEEL, Basil Nabeel BANIAMER, Abdallah Najeh ALETAYWI
Journal of Multiple Sclerosis Research - 2026;6(1):31-38
Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammatory demyelinating lesions within the central nervous system. Bruton's tyrosine kinase inhibitors (BTKis) modulate immune responses by inhibiting a key enzyme involved in B-cell receptor signaling and the activation of other immune cells. However, the efficacy and safety of BTKi remain controversial, and more comprehensive studies are required. We searched PubMed, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) evaluating BTKis for MS through October 1, 2024, and identified six RCTs. A total of 2,960 patients from these trials were included to examine the efficacy and safety of BTKi in MS treatment. The included BTKi were evobrutinib [25,45, and 75 mg once daily; 75 mg twice daily (BID)], fenebrutinib (200 mg BID), and tolebrutinib. Across the included studies, evobrutinib-particularly at 75 mg BID-reduced the number of new T1 gadolinium-enhancing lesions and T2 lesion burden compared with placebo, with a favorable safety profile. In addition, its long-term efficacy was supported by stable outcomes and sustained safety. Other BTKi demonstrated promising short-term results; however, no long-term data are currently available. In contrast, none of the treatments showed significant changes in Expanded Disability Status Scale scores. Overall, BTKi have shown promising results in the treatment of MS. In particular, evobrutinib may serve as a suitable oral alternative for patients with mild to moderate disease due to its safety and selectivity. Nevertheless, further clinical trials are needed to better evaluate other BTKi and to provide a more comprehensive understanding of their long-term efficacy and safety.
