Adverse Events, CNS Side Effects Vary in sgAHs for Chronic Urticaria

There are no significant differences in serious adverse events (SAEs) and anticholinergic side effects among second-generation H1-antihistamines (sgAHs) compared with placebo for the treatment of patients with chronic urticaria, according to study findings published in Journal of Allergy and Clinical Immunology: In Practice.

Researchers conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) that compared evidence regarding sgAH safety profiles as an individual single dose or with dose escalation for CU. They searched for relevant articles published in the Medline, Embase, PubMed, Cochrane Library, Scopus, and CINAHL databases from inception to July 2, 2022, as well as in a supplemental search in Google Scholar, ongoing trial registries, and other sources with an update on January 20, 2023. The RCTs were included if they reported data regarding adverse events of sgAHs in adolescents or adults aged 12 years and older diagnosed with CU.

The primary outcomes were treatment unacceptability, tolerability, adverse events, SAEs, composite central nervous system (CNS) side effects, and composite anticholinergic side effects.

A total of 48 full-text articles and 2 short reports published between 1991 and 2022 were included in the review and meta-analysis. The studies compared 14 sgAHs with each other or placebo in licensed-dose, up-dosing, dose-ranging, or combinations of sgAHs. The median age of the 7502 participants was 39.0 (SD, 3.9) years.

The NMA estimates for treatment unacceptability (47 trials; n=6757) showed that bilastine 20 mg, cetirizine 10 mg, desloratadine 5 mg, emedastine 4 mg, fexofenadine 240 mg, levocetirizine 5 mg, loratadine 10 mg, mizolastine 10 mg, olopatadine 10 mg, rupatadine 10 mg, and rupatadine 20 mg were more favorable vs placebo for all-cause discontinuation during follow-up (odds ratios [ORs], 0.25-0.60).

Regarding tolerability (42 trials; n=6381), no sgAH treatment comparison had a greater risk for all-cause discontinuation due to adverse events compared with placebo, except for fexofenadine 120 mg, which was unfavorable for tolerability compared with fexofenadine 480 mg (OR, 4.76; 95% CI, 1.03-20.00).

For adverse events (37 trials; n=5806), cetirizine 10 mg, desloratadine 5 mg, emedastine 4 mg, levocetirizine 5 mg, loratadine 10 mg, mizolastine 10 mg, olopatadine 10 mg, rupatadine 10 mg, and rupatadine 20 mg had an increased risk vs placebo (ORs, 1.50-3.01).

In 41 trials (n=6087), cetirizine 10 mg, emedastine 4 mg, levocetirizine 5 mg, loratadine 10 mg, mizolastine 10 mg, and rupatadine 20 mg were more unfavorable for composite CNS side effects vs placebo (ORs, 2.43-5.78). No statistical differences were found for particular sgAH treatments for SAEs (50 trials; n=7419) and anticholinergic side effects (39 trials; n=6012).

The pairwise meta-analyses yielded almost identical results to those of the network analyses, except for treatment unacceptability (cetirizine 10 mg, and rupatadine 10 mg and 20 mg), any adverse events (cetirizine 10 mg, loratadine 10 mg, and rupatadine 10 mg), and CNS side effects (levocetirizine 5 mg, loratadine 10 mg, and mizolastine 10 mg).

Emedastine 4 mg, mizolastine 10 mg, and cetirizine 10 mg were the ranked treatments with unfavorable outcomes regarding safety profiles, especially CNS side effects and any adverse events, according to the multiple outcomes visualized approach.

Limitations of the study include the fact that selective outcome reporting should have been conducted, and the search was limited to studies published in English. Also, some treatment options were based on 1 trial, and potential small study effects may have occurred.

“To better harmonize and compare the efficacy and safety of different treatment interventions, there is a need for standardized reporting of core outcome sets in future CU clinical trials,” conclude the researchers.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.