Article Impact Level: HIGH Data Quality: STRONG Summary of Journal of Allergy and Clinical Immunology, S0091674925006463. https://doi.org/10.1016/j.jaci.2025.06.004 Dr. Alexandro W.L. Chu et al.
Points
- A meta-analysis of 93 studies found standard-dose omalizumab and remibrutinib are among the most effective treatments for improving key patient outcomes in chronic urticaria.
- While cyclosporine may be one of the most effective therapies for reducing urticaria activity, it may also be among the most harmful regarding the frequency of adverse events.
- The biologic dupilumab demonstrated a clear ability to improve urticaria activity; however, its overall effect on quality of life and angioedema activity remains uncertain based on the available data.
- Conventional immunosuppressants, such as azathioprine and dapsone, may offer some improvement in outcomes, while biologics, including benralizumab and tezepelumab, may not differ significantly from a placebo.
- Researchers concluded that omalizumab and remibrutinib offer the most favorable net benefit, whereas the utility of conventional immunosuppressants is less certain due to potential harms.
Summary
A systematic review and network meta-analysis were conducted to synthesize the comparative benefits and harms of systemic treatments for chronic urticaria, informing an update to the AAAAI/ACAAI JTFPP clinical guidelines. Researchers searched seven major databases from inception to February 4, 2025, identifying 93 studies (including 83 randomized trials and 10 nonrandomized studies) with a total of 11,398 participants. The analysis evaluated 42 different interventions, focusing on outcomes such as urticaria activity, angioedema activity, health-related quality of life, and adverse events, with evidence certainty assessed using the GRADE approach.
With high certainty, standard-dose omalizumab (300 mg every 4 weeks) and the novel agent remibrutinib were found to be among the most effective interventions for improving multiple patient-important outcomes. The safety profile of remibrutinib, however, is less certain than that of omalizumab. Dupilumab was effective for improving urticaria activity, but its impact on quality of life and angioedema is uncertain. Conversely, cyclosporine may be highly effective for improving urticaria activity but may also be among the most harmful therapies regarding the frequency of adverse events.
Evidence for other agents was less certain. Azathioprine, dapsone, hydroxychloroquine, mycophenolate, sulfasalazine, and vitamin D may improve outcomes. In contrast, benralizumab, quilizumab, and tezepelumab may not offer benefits over placebo. The findings were consistent across subgroups, concluding that standard-dose omalizumab and remibrutinib offer the most favorable balance of efficacy and safety. At the same time, the net benefit of conventional immunosuppressants remains uncertain.
Link to the article: https://www.jacionline.org/article/S0091-6749(25)00646-3/fulltext
References Chu, A. W. L., Oykhman, P., Chu, X., Rayner, D. G., Bhangal, S., Dam, A., Xu, J., Sheikh, J., Trayes, K. P., Frazier, W. T., Lang, D. M., Beck, L. A., Mathur, S. K., Waserman, S., Thabane, L., Asiniwasis, R. N., Runyon, L., Moellman, J., Oliver, E. T., … Chu, D. K. (2025). Comparative efficacy and safety of biologics and systemic immunomodulatory treatments for chronic urticaria: Systematic review and network meta-analysis. Journal of Allergy and Clinical Immunology, S0091674925006463. https://doi.org/10.1016/j.jaci.2025.06.004
