Rafael José Vieira, Sara Gil-Mata, André Ferreira, Pau Riera-Serra, Antonio Bognanni, Vítor Duarte, Hugo Viegas, Ana Cristina Pequito Pereira, Renato Ferreira-da-Silva, Henrique Ferreira-Cardoso, Manuel Marques-Cruz, João Castro-Teles, Miguel Campos-Lopes, Ana Teixeira-Ferreira, Nuno Lourenço-Silva, José Laerte Boechat, E Borowiack, Ewelina Sadowska, Raquel Albuquerque Costa, Paula Perestrelo, Marta Soares Pereira, Juliana Pereira-Macedo, Despo Ierodiakonou, A. Chu, Izabela Pera Calvi, Maria Inês Torres, Rita A. Silva Ribeiro, Tuuli Thomander, Arunas Valiulis, Iván Chérrez-Ojeda, Anna Bedbrook, Ludger Klimek, Juan Jose Yepes Nuñez, Torsten Zuberbier, João A. Fonseca, Holger J. Schünemann, Jean Bousquet, Bernardo Sousa-Pinto, Elena Azzolini, G.Walter Canonica, Leticia De Las Vecillas, Mark Dykewicz, Lucas Leemann, Gilles Louis, Olga Lourenço, Ana Dantas Neves, Nikolaos G. Papadopoulos, Elena Parmelli, Sanna K. Toppila-Salmi, Marine Savouré, Maria Emilia Paida Torres, Maria Teresa Ventura, Sian Williams, Jaron Zuberbier
BACKGROUND: Oral H1-antihistamines (OAHs) are among the most frequently used medications for the treatment of allergic rhinitis (AR). OBJECTIVE: To perform a systematic review and network meta-analysis comparing the efficacy and safety of individual OAHs in patients with AR. METHODS: We searched 4 electronic bibliographic databases and 3 clinical trial databases for randomized controlled trials assessing adults with perennial or seasonal AR, and comparing (1) OAH versus placebo or (2) different individual OAHs. We performed a network meta-analysis on the Total Nasal Symptom Score, Total Ocular Symptom Score, Rhinoconjunctivitis Quality-of-Life Questionnaire, development of adverse events, and withdrawals due to adverse events. Certainty of evidence for comparisons involving the most clinically relevant second-generation OAHs was assessed using Grading of Recommendations, Assessment and Evaluation approach to network meta-analysis. RESULTS: We included 74 randomized controlled trials (21 on perennial AR and 53 on seasonal AR). Cetirizine, ebastine, bilastine, and rupatadine were among the individual medications associated with the highest efficacy for improving nasal symptoms. For other efficacy outcomes, the most efficacious interventions varied. A similar frequency of adverse events was observed among different individual second-generation OAHs, with serious adverse events being rare. For most comparisons, the certainty of evidence was rated as "low" or "very low," indicating substantial uncertainty regarding the treatment effects. CONCLUSIONS: Although some OAHs seem to be more efficacious than others, most of the differences between individual second-generation medications are trivial or small. In addition, we did not find any relevant differences in the safety profiles of second-generation OAHs.