Chronic urticaria, encompassing chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), affects a substantial portion of the population worldwide and imposes a heavy burden due to persistent symptoms like hives, itching, and angioedema, often inadequately controlled by standard treatments.
Current first-line therapy relies on nonsedating H1-antihistamines, with omalizumab (an anti-IgE biologic) as the mainstay for refractory cases.
However, omalizumab achieves complete resolution in only about 45% of patients and rarely induces lasting remission after discontinuation.
However, omalizumab achieves complete resolution in only about 45% of patients and rarely induces lasting remission after discontinuation.
Excitingly, the therapeutic landscape for refractory CSU has expanded dramatically in recent years, with several new approvals and promising agents targeting both IgE-dependent and non-IgE pathways.
Dupilumab (Dupixent), an IL-4/IL-13 inhibitor, gained FDA approval in April 2025 for H1-antihistamine-refractory CSU in adults and adolescents ≥12 years, validating the role of type 2 inflammation in CSU pathogenesis.
Remibrutinib (Rhapsido), the first oral Bruton's tyrosine kinase inhibitor (BTKi), received FDA approval in September 2025 for adults with symptomatic CSU despite antihistamines. Phase 3 trials (REMIX-1 and REMIX-2) showed rapid, significant reductions in Urticaria Activity Score (UAS7), itch, and hives, with about one-third of patients achieving complete symptom resolution by week 12.
Omalizumab biosimilars, such as Omlyclo are offering more accessible IgE-targeted options.
Emerging c-Kit inhibitors like barzolvolimab have demonstrated efficacy in CSU and CIndU, with effects persisting post-treatment in trials, highlighting mast cell targeting potential.
Other mechanisms in development include additional BTKis, JAK inhibitors, TYK2/JAK inhibitors, MRGPRX2 antagonists, and more.
While some candidates (e.g., fenebrutinib, THB001, EP262) were discontinued due to safety issues, and others (e.g., tezepelumab, mepolizumab, benralizumab, lirentelimab, AK006) due to insufficient efficacy, these outcomes have refined our understanding of CSU pathways.
While some candidates (e.g., fenebrutinib, THB001, EP262) were discontinued due to safety issues, and others (e.g., tezepelumab, mepolizumab, benralizumab, lirentelimab, AK006) due to insufficient efficacy, these outcomes have refined our understanding of CSU pathways.
Overall, 2025 marked a transformative year for CSU management, shifting toward more targeted, effective systemic therapies - both injectable biologics and convenient oral options - that promise better symptom control and quality of life for patients with refractory disease. The pipeline remains active, with phase 3 programs underway to further broaden choices.
References:
https://www.jaci-inpractice.org/article/S2213-2198(25)01144-4/fulltext
References:
https://www.jaci-inpractice.org/article/S2213-2198(25)01144-4/fulltext