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Up-Dosing Antihistamines in Chronic Spontaneous Urticaria: Efficacy and Safety. A Systematic Review of the Literature

Iriarte Sotés P1*, Armisén M2*, Usero-Bárcena T3*, Rodriguez Fernández A4, Otero Rivas M5; Gonzalez MT2, Meijide Calderón A6 and Veleiro B7*, from Urtigal, the Galician Group of Interest in Urticaria

1Allergology Department, Complexo Hospitalario Universitario de Ferrol
2Allergology Department, Complexo Hospitalario Universitario de Santiago
3Dermatology Department Complexo Hospitalario Universitario de Ferrol
4Allergology Department, Centro de Especialidades Mollabao, Pontevedra
5Dermatology Department, Hospital Universitario Lucus Augusti, Lugo
6AllergologyDepartment, Complexo Hospitalario Universitario de Vigo
7Allergology Department, Complexo Hospitalario Universitario A Coruña
*These authors have participated equally in the preparation of this manuscript

J Investig Allergol Clin Immunol 2021; Vol. 31(4)
doi: 10.18176/jiaci.0649

Background: According to current guidelines, oral antihistamines are the first line treatment for chronic spontaneous urticaria (CSU). Up-dosing antihistamines up to fourfold the licensed dose is recommended if control is not achieved. Such indications are based mainly on expert´s opinions.
Objectives: To critically review and analyze clinical evidence regarding to efficacy and safety of higher-than-licensed dosage of second-generation oral antihistamines in CSU treatment.
Material and methods: A systematic literature review following a sensitive search strategy was performed. All articles published in MEDLINE, EMBASE, and Cochrane Library between 1961 and October 2018 were examined. Publications with CSU patients treated with prescribed second-generation antihistamines in monotherapy comparing with either placebo, licensed dosage and/or higher dosage were included. Articles were evaluated by peer revisors. Quality was evaluated using Jadad and Oxford scores.
Results: We identified 337 articles, 14 were included in the final evaluation; 6 focus on fexofenadine, 2 on cetirizine, levocetirizine, rupatadine and desloratadine, and 1 for ebastine and bilastine. Only 5 studies were placebo-controlled. The number of included patients ranged from 20 to 439. Observation lapse was ≤ 16 weeks. High fexofenadine doses produced dose-dependent significant response and controlled urticaria in a majority of patients. Cetirizine, levocetirizine, rupatadine and bilastine showed an increased effectiveness when up-dosing. Most frequent adverse events were headache and drowsiness.
Conclusion: The low quality and heterogeneity of the articles reviewed made impossible to reach any robust conclusions and unveil the need to develop large-scale randomized clinical trials.

Key words: Chronic urticaria, Antihistamines, Treatment, Up-Dosing, Efficacy, Safety, Systematic review