Treatment dose increase versus comedication in allergic rhinitis: Systematic review with dose-response network meta-analysis protocol

Background: In patients with allergic rhinitis who remain uncontrolled despite being treated with standard daily doses of a single medication, strategies that can be followed to achieve adequate symptom control include (i) increasing the medication dose, or (ii) adding an additional medication (co-medication). However, it is not known which one of these two strategies is more effective. Objectives: This article describes a protocol of a systematic review with dose-response network meta-analysis aiming at comparing different intranasal and oral medications in patients with seasonal or perennial allergic rhinitis. Methods: We will search four electronic bibliographic databases and three clinical trials databases for randomized controlled trials (i) assessing adults or children with seasonal or perennial allergic rhinitis, and (ii) evaluating the effect of intranasal medications, oral medications or combinations of any intranasal and/or oral medications for allergic rhinitis. Assessed outcomes will include the Total Nasal Symptom Score, the Total Ocular Symptom Score and the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). We will assess the methodological quality of included primary studies by using the Cochrane riskof-bias tool. Certainty in the body of evidence for the analysed outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach for network meta-analyses (GRADE-NMA). We will perform a frequentist dose-response model-based network meta-analysis. Sensitivity analyses will be performed by separately analysing data for seasonal and perennial allergic rhinitis. Conclusion: This protocol describes the methodology of a systematic review that will fit dose-response network meta-analysis models in the comparison between different intranasal and oral medications. The findings of this systematic review will support recommendations in the Allergic Rhinitis and its Impact on Asthma (ARIA) 2024-2025 guidelines.