Comparative Efficacy and Acceptability of Licensed Dose Second-Generation Antihistamines in Chronic Spontaneous Urticaria: A Network Meta-Analysis

J Allergy Clin Immunol Pract. 2021 Feb;9(2):956-970.e57. doi: 10.1016/j.jaip.2020.08.055. Epub 2020 Sep 8.


Background: Licensed dose second-generation H1-antihistamines (sgAHs) are the first-line treatment in chronic spontaneous urticaria (CSU). However, the available evidence up to the present is insufficient to rank sgAHs in terms of their efficacy.

Objectives: To study the comparative efficacy and acceptability of all licensed dose sgAHs in CSU treatment.

Methods: We searched PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Web of Science for randomized controlled trials (RCTs) that included licensed dose sgAHs in CSU treatment up until March 2020. A network meta-analysis was performed to estimate the standardized mean difference (SMD) and 95% confidence interval (CI) from both direct and indirect evidence for efficacy outcomes. The primary outcome was the total symptom score (TSS) changes from baseline. Secondary outcomes were changes in pruritus score and wheal score from baseline. The acceptability was estimated using odds ratios.

Results: We identified and included 22 RCTs with 3943 patients for evidence synthesis. Olopatadine, fexofenadine, bilastine, rupatadine, and levocetirizine were more efficacious than placebo in TSS. Olopatadine was ranked first for all efficacy outcomes (TSS: SMD -1.26 [95% CI: -1.94 to -0.58], pruritus score: SMD -0.82 [95% CI: -1.30 to -0.35], and wheal score: SMD -0.65 [95% CI: -1.10 to -0.55]). The acceptability of all included sgAHs was not inferior to the placebo.

Conclusions: Olopatadine, fexofenadine, bilastine, rupatadine, and levocetirizine demonstrate superior therapeutic efficacy to placebo for the treatment of patients with CSU. Because of the low to very low quality of almost all studies included in this study, rigorous head-to-head trials are needed to confirm our findings.

Keywords: Acceptability; Antihistamines; Chronic idiopathic urticaria; Chronic spontaneous urticaria; Comparison; Efficacy; Licensed dose; Network meta-analysis; Second-generation antihistamines; Systematic review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chronic Disease
  • Chronic Urticaria*
  • Histamine H1 Antagonists, Non-Sedating*
  • Humans
  • Network Meta-Analysis
  • Pruritus
  • Urticaria* / drug therapy


  • Histamine H1 Antagonists, Non-Sedating