Omalizumab, Remibrutinib Most Effective for Refractory Chronic Urticaria

A study found that standard-dose omalizumab and remibrutinib are the most effective drugs for patients with chronic urticaria refractory to antihistamines.1

“Dupilumab is also among the most effective in reducing urticaria activity, although there is a paucity of evidence for its effects on angioedema-specific outcomes,” wrote investigators, led by Alexandro W.L. Chu, MD, from the department of medicine at McMaster University in Canada.

Chronic urticaria, characterized by itchy wheals or angioedema, lasts ≥ 6 weeks. Patients who do not respond to antihistamines have several other treatment options, but it is unknown how these alternative systemic treatments compare with one another.

For individuals with refractory chronic urticaria, guidelines currently recommend the use of omalizumab and cyclosporine. Other alternative treatments include corticosteroids (oral prednisone), leukotriene receptor antagonists (montelukast and zafirlukast), dapsone, sulfasalazine, hydroxychloroquine, methotrexate, autologous serum therapy, mycophenolate mofetil, phototherapy, warfarin, immunoglobulin, doxepin, and topical clobetasol.2

In this meta-analysis, investigators compared the benefits and harms of systemic treatments for chronic urticaria. They searched Medline, Embase, Central, Chinese Biomedical.1 Databases, China National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wanfang from inception to February 4, 2025, for randomized trials on systemic immunomodulatory treatments for chronic urticaria. The analysis assessed urticaria activity (itch and wheal score), angioedema activity, health-related quality of life, and adverse events.

The study included 93 studies (83 randomized and 10 non-randomized studies), with a total of 11,398 participants (adults and adolescents) who had a mean age of 41.6 years, 68% of females, and a mean UAS7 of 30.48. These trials comprised of 42 interventions; studies had a median duration of 12 weeks (range, 1 – 52 weeks).

The study found, with high certainty, that standard-dose omalizumab (300 mg every 4 weeks) and remibrutinib are the most effective for improving patient outcomes. However, the safety profile of remibrutinib is less certain.

Dupilumab, although improving urticaria activity, had an uncertain impact on quality of life. No trials examined dupilumab’s impact on angioedema activity.

Investigators found cyclosporine may be the most effective for improving urticaria activity, yet the most harmful in increasing the frequency of adverse events. With uncertain evidence, the study showed azathioprine, dapsone, hydroxychloroquine, mycophenolate, sulfasalazine, and vitamin D may improve outcomes, whereas benralizumab, quilizumab, and tezepelumab may not have meaningful improvement versus placebo. The findings were consistent across age groups and baseline severity.

“These findings are relevant to clinical decision-making, highlighting the values- and preference-sensitive decisions that patients with chronic urticaria will face when multiple treatment options demonstrate similar efficacy,” investigators wrote.

For instance, comorbidities may help determine what treatment to prescribe to a patient. A patient with concomitant food allergy may prefer omalizumab, whereas a patient with chronic rhinosinusitis with nasal polyposis or atopic dermatitis may prefer dupilumab.

Availability of medications or financial constraints can also determine what treatment to prescribe, as well as other factors such as fear of needles, cost, convenience of administration, long-term safety, and benefits vs harms.

“Our findings support the need for robust head-to-head randomized trials among biologics, small molecule inhibitors, and classic immunomodulators, which, while ideal, has thus far been challenging to implement in asthma,” investigators wrote. “Thus, this study may provide the best available comparative evidence to inform decision-making. Exploring urticaria phenotypes may also aid in the precision of therapy choices. Strengthening this evidence base will refine their optimal role in chronic urticaria management, both in resource-rich and resource-constrained settings, allowing for clearer differentiation of interventions among effectiveness categories.”

References

1. Chu AWL, Oykhman P, Chu X, et al. Comparative efficacy and safety of biologics and systemic immunomodulatory treatments for chronic urticaria: Systematic review and network meta-analysis. J Allergy Clin Immunol. Published online July 11, 2025. doi:10.1016/j.jaci.2025.06.004

2. Mehta A, Godse K, Patil S, Nadkarni N, Gautam M. Treatment of Refractory Chronic Urticaria. Indian J Dermatol. 2015 May-Jun;60(3):230-7. doi: 10.4103/0019-5154.156325. PMID: 26120147; PMCID: PMC4458932.