Treatment Dose Increase Versus Co-Medication in Allergic Rhinitis: Systematic Review With Dose–Response Network Meta-Analysis

Background: To achieve adequate symptom control, patients with allergic rhinitis (AR) often need to increase their medication dose or add other treatments (co-medication). We aimed to perform a systematic review to compare the efficacy and safety of AR medications for increased dose versus co-medication. Methods: We searched four bibliographic databases and three trial databases for randomised controlled trials assessing the effect of intranasal and/or oral medications in patients of all ages with seasonal or perennial AR. We performed pairwise meta-analysis based on direct evidence to compare (i) non-standard versus standard treatment doses, and (ii) co-medication strategies versus monotherapy using standard doses. Furthermore, we fitted dose–response network meta-analysis (NMA) to obtain projected estimates for comparisons involving two times the standard dose of AR medications in monotherapy versus co-medication with the standard dose of the same medications. We assessed the certainty of evidence using GRADE for NMA. Results: We included 262 studies. Co-medication schemes involving oral antihistamines (OAH) + intranasal corticosteroids (INCS) resulted in higher improvements of nasal symptoms and quality of life than doubling the dose of OAH. However, doubling the dose of intranasal medications led to better results than having intranasal medications + OAH. Doubling the dose of INCS was associated with higher efficacy than adding intranasal antihistamines (INAH). No relevant safety differences were found between treatment strategies. Conclusions: Results favoured (i) doubling the dose of intranasal medications versus adding OAH, and (ii) adding INCS to OAH over doubling the dose of OAH. This study will inform the ARIA-EAACI 2024–2025 guidelines.