Efficacy and Safety of Combined Pharmacotherapies in Moderate‐to‐Severe Allergic Rhinitis: A Network Meta‐Analysis

Combination pharmacotherapies are often selected for moderate-to-severe allergic rhinitis (AR), particularly when monotherapies do not control symptoms effectively. However, few studies have compared the efficacy and safety of different combination regimens. Therefore, we performed this study to investigate the clinical benefits of different combination strategies for moderate-to-severe AR. Electronic databases were searched (inception-May 31, 2024) for randomized controlled trials involving combination therapies for treating moderate-to-severe AR. The medication classes included intranasal corticosteroids (INCS), intranasal antihistamines (INAH), oral antihistamines (OAH), and oral leukotriene receptor antagonists (LTRA). A network meta-analysis with a random-effects model was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Forty-eight eligible studies with 17,188 participants were included. In this meta-analysis, INAH and INCS, OAH and INCS, and INCS were the most effective in improving Total Nasal Symptom Score, and INAH and INCS, INAH, and INCS most effectively enhanced the total ocular symptom score. INCS and LTRA, OAH and INCS, and INAH and INCS showed the greatest benefit in improving the Rhinitis Quality of Life Questionnaire. Although INCS and INAH and INAH increased the risk of overall adverse events, specific adverse events predominantly included a bitter taste. Combination therapies demonstrated superior efficacy compared to monotherapies overall. The INAH and INCS combination provided the greatest advantage in symptom improvement. The combination of OAH and INCS could be a viable alternative treatment option if the bitter taste is unacceptable. Our findings provide novel insights into optimizing personalized combination therapies.