Comparative Safety Profiles of Individual Second-Generation H1-Antihistamines for the Treatment of Chronic Urticaria: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

The comparative safety and/or dosing regimens of individual second-generation H1-antihistamines (sgAHs) in patients with chronic urticaria (CU) remain poorly elucidated.To compare the safety profiles of individual sgAHs and/or dosing regimens in adolescents or adult patients with CU using a systematic review and network meta-analysis of all available evidence.With limited English publications, electronic databases and gray literature were searched for randomized clinical trials from inception, with searches last updated on January 20, 2023. Relevant safety outcomes included treatment unacceptability (all-cause discontinuation), tolerability (discontinuation due to any adverse events), adverse events, serious adverse events, central nervous system (CNS) side effects, and anticholinergic side effects. Regarding the network estimates, the probability of being associated with the highest adverse outcome risk was estimated for each treatment comparison.Fifty-one randomized clinical trials with 14 individual sgAHs and different dosing regimens, involving 7502 participants, were included. On the basis of the findings from network meta-analyses, variations in sgAH treatment comparisons were observed regarding the unacceptability of treatment, tolerability, adverse events, and CNS side effects. There were no statistically significant differences between the results of sgAH treatment for serious adverse events and those for anticholinergic side effects. On the basis of the ranking of safety profiles, emedastine 4 mg, mizolastine 10 mg, and cetirizine 10 mg were the top 3 ranked treatments with unfavorable safety profiles associated with CNS side effects and any adverse events.These findings suggest evidence of variations in safety profiles among sgAHs for CU treatment, particularly in terms of adverse events and CNS side effects.