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Choices of second-generation antihistamines in chronic spontaneous urticaria

Published online: September 7, 2020

Urticaria is one of the common allergic skin problems worldwide. It is not only a bad itch, but also can be an embarrassment resulting from the unpleasant widespread rash and/or marked swelling of the soft tissue (angioedema), particularly in severely affected patients, which impacts their quality of life and mental health. The classification of urticaria fundamentally depends on the duration and cause. Chronic spontaneous urticaria (CSU) refers to urticaria that persists more than 6 weeks without any specific triggers. Although no inducible factors are identified, the well-known crucial mediator contributing to the symptoms in CSU is histamine. Second generation antihistamines (sgAHs) are the preferred option recommended by all clinical practice guidelines, owing to their favorable safety profiles compared to first generation AHs. Various choices of sgAHs are approved in the indication of CSU, albeit without an evidence-based ranking in terms of their efficacy.

In a research article recently published in The Journal of Allergy and Clinical Immunology: In Practice, Phinyo et al. conducted a network meta-analysis (NMA) to compare the efficacy and acceptability of all licensed dose sgAHs in CSU treatment. Twenty-two randomized controlled trials with 3943 patients were included. Ten sgAHs, namely acrivastine, bilastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mizolastine, and rupatadine were comparatively analyzed for their efficacy, primarily assessed by changes in total symptom score. They found that of all licensed dose sgAHs in this NMA, olopatadine, fexofenadine, bilastine, rupatadine, and levocetirizine demonstrated superior therapeutic efficacy to placebo for the treatment of patients with CSU. No statistically significant different outcome among the active drugs except levocetirizine was superior to rupatadine by indirect analysis. The acceptability of all drugs was not inferior to placebo.

A few limitations should be considered before implementing the results from this analysis into the clinical practice. Firstly, a few commonly used sgAHs, such as acrivastine and ebastine, were not included in this comparison due to the unmet predefined inclusion criteria. Secondly, the statistical issues including the difference of units and scales of measurement across trials, the imputation of missing data, and a low quality of evidence used for synthesis may hinder the reliability and the internal validity of the NMA estimates. Therefore, the direct evidence from further well-designed comparative head-to-head studies is still of paramount importance.

NMA is the best methodology that one can perform scientifically to compare the efficacy among various active comparators that may otherwise be infeasible in a single study. The findings from this NMA could guide physicians who treat CSU patients regarding choices of sgAHs in terms of their efficacy. However, other factors including safety, cost, patient preference, and the availability of these drugs should be considered when selecting sgAHs in practice.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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