Multiple sclerosis updates and the safety and efficacy of Bruton tyrosine kinase inhibitors in it: A systematic review

Abstract

Background: Multiple sclerosis (MS) is a chronic neurodegenerative and autoimmune disease characterized by CNS inflammation and demyelination. Although current disease-modifying therapies (DMTs) can reduce peripheral immune responses, their impact on CNS-compartmentalized inflammation remains limited. Bruton Tyrosine Kinase inhibitors (BTKis) have emerged as promising oral agents targeting both B cells and microglia.

Objective: To evaluate the safety profiles and effectiveness of two BTK inhibitors- Tolebrutinib and Evobrutinib in the management of relapsing multiple sclerosis.

Methods: A literature search was conducted using PubMed, Embase, and Scopus for randomized controlled trials published between 2020 and 2024. Studies comparing Evobrutinib and Tolebrutinib in MS patients were screened and evaluated based on predetermined inclusion and exclusion criteria. Four relevant RCTs were matched and examined in more detail.

Results: On MRI, both BTK inhibitors showed decreases in gadolinium-enhancing lesions; Tolebrutinib demonstrated dose-dependent efficacy in reducing new Gd-enhancing lesions and T2 lesion counts, with optimal effects at 60 mg daily. Evobrutinib showed dose-dependent decreases in serum neurofilament light (NfL) levels and relapse rates, with twice-daily dosing providing greater BTK inhibition and clinical benefit. Nasopharyngitis, temporary increases in liver enzymes, and mild gastrointestinal symptoms were among the frequent side effects for both agents. The included studies did not report any direct clinical comparisons of CNS penetration or microglial modulation.

Conclusion: With good safety and efficacy profiles in treating relapsing multiple sclerosis, both of the BTKis (Evobrutinib and Tolebrutinib) show promise. Both have promise as oral treatments of the future, but Tolebrutinib might have better effects on the central nervous system. To confirm long-term results and determine their role in progressive MS, more phase III trials are necessary.

Keywords: BTK inhibitors; Evobrutinib; Multiple Sclerosis; Neuroinflammation; Tolebrutinib.