Efficacy and Safety of Tyrosine Kinase Inhibitors in the Treatment of Multiple Sclerosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Fahad Amin1, Muhammad Fateh Alam Bhatty1, Huzaifa Nadeem1, Sarmad Chattha1, Fatima Rasool1, Hassan Asif1, Hafiza Maheen Fatima1
1King Edward Medical University
Objective:
This systematic review and meta-analysis aimed to evaluate the efficacy of tyrosine kinase inhibitors in patients with multiple sclerosis by assessing their effects on gadolinium-enhancing lesions, T2 lesion rates, disability progression measured by the Expanded Disability Status Scale (EDSS), and relapse rates, while also determining their safety profile with a particular focus on serious adverse events and hepatotoxicity.
Background:
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, characterized by T-cell–mediated myelin destruction, demyelination, and neurological dysfunction. Tyrosine kinase (TK) inhibitors have recently emerged as potential therapeutic agents; however, their clinical efficacy and safety remain uncertain.
Design/Methods:
Following PRISMA 2020 guidelines, PubMed, Cochrane Library, EU Trials, Scopus, and ClinicalTrials.gov were searched through August 2025 for randomized controlled trials comparing TK inhibitors with placebo. Primary outcomes included changes in gadolinium-enhancing and T2 lesion rates, with secondary outcomes of EDSS, relapse rate, and safety events. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Pooled risk ratios (RRs), mean differences (MDs), and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated under a random-effects model.
Results:
Seven RCTs with 2392 patients (TK: 1627; placebo: 765) were included. TK inhibitors significantly reduced gadolinium-enhancing lesions (SMD = –0.34, 95% CI [–0.55, –0.12]) and T2 lesion rates (RR = 0.48, 95% CI [0.30, 0.76]). A modest EDSS improvement was observed (MD = –0.10, 95% CI [–0.17, –0.02]), but no significant effect on relapse rates (RR = 0.96, 95% CI [0.56, 1.66]). TK inhibitors increased risks of serious adverse events (RR = 1.59, 95% CI [1.23, 2.06]) and hepatotoxicity (RR = 2.00, 95% CI [1.08, 3.70]).
Conclusions:
TK inhibitors reduce lesion activity and modestly improve disability in MS but do not lower relapse risk and are associated with increased adverse events. Their use requires close monitoring, and further long-term studies are needed.
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