Although second-generation H1 antihistamines remain the first-line treatment for chronic spontaneous urticaria (CSU), a significant proportion of patients experience inadequate symptom control, highlighting the ongoing need for more effective and targeted treatment strategies. We conducted a systematic review and meta-analysis of 5 randomized controlled trials (RCTs) comparing Bruton’s tyrosine kinase (BTK) inhibitors with placebo at 4, 8, and 12 weeks in patients with CSU. We searched PubMed, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) from inception to April 2025. The primary outcomes assessed included the Weekly Urticaria Activity Score (UAS7), complete absence of pruritus and urticaria (UAS7 = 0), well-controlled CSU (UAS7 ≤ 6), and safety outcomes. Across 5 included RCTs, 1071 (71.93%) patients received BTK inhibitors. BTK inhibitors significantly increased the likelihood of achieving UAS7 = 0 at week 4 [risk ratio (RR) 5.64; 95% confidence interval (CI) 1.04-30.70; P = .05], week 8 (RR 3.78; 95% CI 2.48-5.76; P < .00001), and week 12 (RR 2.68; 95% CI 1.28-5.62; P = .02). Consistent findings were observed for UAS7 ≤ 6 at week 4 (RR 4.30; 95% CI 3.06-6.03; P < .00001), week 8 (RR 2.60; 95% CI 2.02-3.33; P < .00001), and week 12 (RR 2.05; 95% CI 1.68-2.50; P < .00001). Neither the incidence of adverse events (AEs; RR 1.06; 95% CI 0.84-1.33; P = .47), nor serious AEs (RR 1.17; 95% CI 0.34-4.02; P = .71) was significantly different between groups. BTK inhibitors offer a valuable, safe, and effective treatment option for CSU, particularly in cases that are refractory to second-generation H1 antihistamines.

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Bruton’s Tyrosine Kinase Inhibitors for Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis