Second-generation H1 antihistamines for the treatment of chronic urticaria: a network meta-analysis

To evaluate the efficacy and safety of 10 commonly used second-generation H1 antihistamines (cetirizine, levocetirizine, loratadine, desloratadine, ebastine, bilastine, olopatadine, rupatadine, fexofenadine, and mizolastine) at licensed doses in treating chronic urticaria using network meta-analysis.

Seven electronic databases were searched, including PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Service System. Relevant literature from inception to the end of December 2025 was retrieved. Studies meeting the criteria were selected, and network meta-analysis was performed using Stata 16 software.

A total of 54 studies involving 7,290 patients were included. Network meta-analysis indicated that olopatadine, mizolastine, bilastine, and levocetirizine were more effective than placebo in improving total symptom scores. All 10 drugs were superior to placebo in reducing itching scores, although only fexofenadine achieved statistical significance. For reducing wheal scores, ebastine was significantly more effective than mizolastine and loratadine. Regarding adverse reactions, no significant differences were observed between any of the drugs and placebo, with fexofenadine having the lowest adverse reaction rate. Sensitivity analyses excluding highrisk studies confirmed the robustness of findings across all outcomes.

Based on current evidence, olopatadine at licensed dose exhibited the best efficacy in reducing total symptom scores. Fexofenadine was most effective for improving itching scores and ebastine was optimal for reducing wheal scores. In addition, fexofenadine had the lowest incidence of adverse reactions. However, the conclusions of this study still need to be validated by further high-quality randomized controlled trials.