Time to Meaningful Clinical Response Across Approved and Emerging Therapies for Antihistamine-Refractory Chronic Spontaneous Urticaria: A Network Meta-Analysis

Background/Objectives: Several novel biologics and small-molecule therapies have emerged for the treatment of antihistamine-refractory chronic spontaneous urticaria (CSU), yet no study has directly compared their speed of response. This study aims to provide indirect evidence on the relative time to meaningful clinical response across approved and investigational therapies using a Bayesian network meta-analysis. Methods: Phase 2 and phase 3 randomized controlled trials reporting UAS7 scores in a graphical format for antihistamine-refractory CSU were included. The primary outcome was the mean time in weeks to minimal clinically important difference (MCID), defined as a UAS7 reduction of 10 points. Data were extracted using WebPlotDigitizer (v4.7) and analyzed via Bayesian random-effects network meta-analysis in MetaInsight (v6.4.0), with placebo as the reference node. Results: All drugs except rilzabrutinib 400 mg daily demonstrated faster mean time to MCID than placebo. Fenebrutinib had the fastest mean time to MCID (0.67–0.76 weeks), and tezepelumab the slowest (5.41–5.65 weeks). Only omalizumab 300 mg every 4 weeks, dupilumab 300 mg every 2 weeks, and ligelizumab 72 mg and 120 mg every 4 weeks achieved statistically significant reductions compared with placebo. All treatments had wide credible intervals reflecting limited direct comparisons. Conclusions: This is the first network meta-analysis comparing time to meaningful symptom control across therapies for antihistamine-refractory CSU. Omalizumab, dupilumab, and ligelizumab demonstrated statistically significant reductions in time to MCID compared with placebo. Head-to-head trials with standardized outcome reporting would enable more definitive comparative conclusions.