ARIA 2024-2025 guideline panel. Efficacy and safety of oral antihistamines for allergic rhinitis: Network meta-analysis.

Vieira RJ, Gil-Mata S, Ferreira A et al. J Allergy Clin Immunol Pract. 2026 Feb 16:S2213-2198(26)00140-6. doi: 10.1016/j.jaip.2025.12.034. 

Highlights

• What is already known about this topic? Oral antihistamines are one of the mainstays of the pharmacological management of allergic rhinitis, being widely available and affordable.

• What does this article add to our knowledge? Oral antihistamines are effective in improving rhinitis symptoms and quality-of-life. Cetirizine, ebastine, bilastine and rupatadine were among the individual medications associated with the highest efficacy for improving nasal symptoms.

• How does this study impact current management guidelines? This systematic review will inform the Allergic Rhinitis and its Impact on Asthma (2024-2025) guidelines. In particular, it will provide evidence on the efficacy and safety of individual oral antihistamines.

Abstract

Background

Oral H1-antihistamines (OAH) are among the most frequently used medications for the treatment of allergic rhinitis (AR).

Objective

To perform a systematic review and network meta-analysis comparing the efficacy and safety of individual OAH in patients with AR.

Methods

We searched four electronic bibliographic databases and three clinical trial databases for randomized controlled trials assessing adults with perennial or seasonal AR, and comparing (i) OAH versus placebo or (ii) different individual OAH. We performed a network meta-analysis on the Total Nasal Symptom Score, Total Ocular Symptom Score, Rhinoconjunctivitis Quality-of-Life Questionnaire, development of adverse events, and withdrawals due to adverse events. Certainty of evidence for comparisons involving the most clinically relevant second-generation OAH was assessed using GRADE-NMA.

Results

Summary of the network meta-analysis results
of the comparisons between each main oral
antihistamine with placebo 

We included 74 randomized controlled trials (21 on perennial AR and 53 on seasonal AR). Cetirizine, ebastine, bilastine and rupatadine were among the individual medications associated with the highest efficacy for improving nasal symptoms. For other efficacy outcomes, the most efficacious interventions varied. A similar frequency of adverse events was observed among different individual second-generation OAH, with serious adverse events being rare. For most comparisons, the certainty of evidence was rated as “low” or “very low”, indicating substantial uncertainty regarding the treatment effects.

Conclusion

Although some OAH seem to be more efficacious than others, most differences between individual second-generation medications are trivial or small. In addition, we did not find relevant differences in the safety profiles of second-generation OAH.

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