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Uncertainty over the efficacy of up-dosing antihistamine in chronic urticaria

Between 0.5 and 1% of the population experience chronic spontaneous urticaria (CSU) which is characterised by recurrent pruritic wheals and/or angioedema that can persist for up to six weeks.

While the precise cause of CSU remains unclear, contemporary European guidelines advocate the use of second-generation antihistamines as a first-line treatment for the condition. Although these drugs can be effective, for patients in which symptom control remains inadequate, the guidance recommends up-dosing to four times the recommended dose as a second-line treatment option.

This latter commendation is based on expert opinion and for this study, a team from the Allergology Department, Complexo Hospital, A Coruna, Spain, set out to review the available evidence to support this approach. They included studies published in English or Spanish with patients at least 12 years of age with CSU on regular (as opposed to “on-demand”) therapy with a second-generation antihistamine. Other inclusion criteria were that the study should have a single antihistamine (rather than a combination), a placebo arm and using the drug at a higher than recommended dosage.

In total and after removal of duplicates and exclusions, only 14 articles were analysed in detail including 20 to 439 patients. Six studies focused on fexofenadine (up-dosing to 720 mg), 2 on cetirizine, levocetirizine, rupatadine, desloratadine and 1 trial with either ebastine or bilastine. Furthermore, only 5 of these trials were placebo controlled and all studies lasted between 2 and 8 weeks except for one fexofenadine trial which lasted 16 weeks. A higher dose of fexofenadine produced a dose-dependent significant response and controlled CSU in the majority of patients. Commenting on their findings, the authors noted that of the 14 trials, only 6 were of high quality and that the high level of heterogeneity in sample size, design, duration etc, which made it very difficult to make comparisons. Interestingly, they also note that despite current guideline recommendations, most studies did not find a significant impact on symptom control from up-dosing.

The authors concluded that while up-dosing appears both effective and safe, there is a lack of evidence to support this approach and called for further studies to validate the recommendations in guidelines.

Iriarte SP T et al. Up-dosing antihistamines inn chronic spontaneous urticaria: efficacy and safety. A systematic review of the literature. J Investig Allergol Clin Immunol 2020 doi: 10.18176/jiaci.0649