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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\u2010to\u2010severe AR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Electronic databases were searched (inception\u2010May 31, 2024) for randomized controlled trials involving combination therapies for treating moderate\u2010to\u2010severe AR. The medication classes included intranasal corticosteroids (INCS), intranasal antihistamines (INAH), oral antihistamines (OAH), and oral leukotriene receptor antagonists (LTRA). A network meta\u2010analysis with a random\u2010effects model was performed following the Preferred Reporting Items for Systematic Reviews and Meta\u2010Analyses guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty\u2010eight eligible studies with 17,188 participants were included. In this meta\u2010analysis, 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.23578","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T03:32:45Z","timestamp":1743219165000},"page":"898-914","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Efficacy and Safety of Combined Pharmacotherapies in Moderate\u2010to\u2010Severe Allergic Rhinitis: A Network Meta\u2010Analysis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1080-4267","authenticated-orcid":false,"given":"Yuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Allergy Beijing Tongren Hospital Capital Medical University  Beijing China"},{"name":"Department of Otolaryngology Head and Neck Surgery Beijing Tongren Hospital Capital Medical University  Beijing China"},{"name":"Beijing Laboratory of Allergic Diseases 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