To evaluate the efficacy of Bruton’s Tyrosine Kinase (BTK) inhibitors in the treatment of Multiple Sclerosis (MS).

MS is an autoimmune demyelinating disease of brain and spinal cord, causing intermittent episodes of physical and cognitive impairments. BTK inhibitors have potential therapeutic benefit, but their clinical efficacy remains inconclusive.

PubMed, Cochrane Library, and Clinicaltrials.gov were systematically searched for randomized controlled trials that assessed BTK inhibitors in MS. Primary outcomes were new T1 Gadolinium lesions and new/enlarging T2 lesions (3.0T MRI). Secondary outcomes included annualized relapse rate, disability progression sustained for 3 and 6 months, and disability improvement sustained for 6 months. Meta-analysis was performed in R (meta, metafor packages). Binary outcomes were estimated as odds ratios, and continuous outcomes were measured as mean di?erences with 95% CLs; heterogeneity was assessed with I².

Thirteen studies (6,360 participants; mean age 41.95 ± 9.20 years; 35.8% male, 64.2% female) were included. BTK inhibitors as an intervention showed a signi?cant improvement in disease progression at 3 months, measured as an increase from baseline EDSS score of 1.0 point more  [OR: 0.80, 95% CI 0.70–0.92]. Placebo group was associated with signi?cantly higher incidence of severe adverse e?ects [OR: 1.35,95%CI 1.08–1.69] and an increase in enlarging T1 Gd lesions [MD: 0.17,95%CI 0.10 to 0.24]. Changes in enlarging T2 Gd lesions were statistically insigni?cant [MD:-0.33,95%CI -1.00 to 0.34]. Of the 12 outcomes, three showed signi?cant differences. For disease progression at 6 months, a trend toward benefit was observed with placebo controls (k=3; OR 0.76, 95% CI 0.64–0.91), but not with teriflunomide (k=2; OR 1.03, 95% CI 0.73–1.46); test for difference was not significant (p=0.13).

This meta-analysis suggests that BTK inhibitors slow the progression of MS. BTK inhibitors signi?cantly reduced 3-month disease progression and T1 Gd lesions, but not the T2 lesions. Moderate heterogeneity needs further exploration.