Biologic therapies for adult chronic urticaria: what works, what doesn't, and why.

INTRODUCTION: Chronic spontaneous urticaria (CSU) remains uncontrolled in many adults despite antihistamines and anti-immunoglobulin E (IgE) therapy. The expanding therapeutic landscape includes validated biologic options, promising investigational mechanisms, and unsuccessful therapeutic programs. AREAS COVERED: This narrative review integrates guidelines, randomized trials, regulatory information, systematic reviews, and cohort studies identified through PubMed/MEDLINE and ClinicalTrials.gov searches through 20 July 2026, with targeted updates during revision. It evaluates anti-IgE therapies, interleukin-4/interleukin-13 blockade, KIT receptor-directed mast-cell depletion, other biologic pathways, and non-biologic small molecules for context. Biomarkers, safety, negative trials, and disease modification are examined. EXPERT OPINION: Omalizumab remains the benchmark therapeutic agent. Dupilumab inhibits interleukin-4/interleukin-13 signaling and is approved for CSU and several type 2 and other inflammatory conditions. Remibrutinib is an oral Bruton tyrosine kinase inhibitor with efficacy across IgE-defined subgroups, supporting its relevance beyond a single proposed autoimmune endotype. Anti-KIT therapy is a leading investigational biologic strategy. Biomarkers should inform response probabilities rather than rigid prescribing decisions. Definitive disease modification remains unproven.