Targeting B-cell Signaling in Multiple Sclerosis: A Meta-analysis of Bruton’s Tyrosine Kinase (BTK) Inhibitors
Hira Zafar1, Hafiz Talha Javed1, Muhammad Hassan Akhtar2, Ali Hamdan2, Alishba Ehtisham2, Zainab Jamshaid2, Eiman Ijaz2, Aina Ashfaq2, Hafsah Gulzar2, Huda Afzal3, Muhammad Qasim Qureshi2
1Department of Neurology, University of Arkansas for Medical Sciences, 2Department of Neurology, King Edward Medical University, 3Department of Neurology, Punjab Medical College
Objective:

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

Background:

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.

Design/Methods:

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 differences with 95% CLs; heterogeneity was assessed with I².

Results:

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 significant 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 significantly higher incidence of severe adverse effects [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 insignificant [MD:-0.33,95%CI -1.00 to 0.34]. Of the 12 outcomes, three showed significant 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).

Conclusions:

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

10.1212/WNL.0000000000213297
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