Abstract
Background
Allergic rhinitis (AR) is a prevalent chronic condition with a substantial global burden. Although numerous therapeutic interventions exist, their comparative efficacy and safety remain unclear. The objective was to evaluate symptomatic interventions for seasonal and perennial AR without comorbid asthma via a systematic review and dose-stratified network meta-analysis (NMA).Methods
We systematically searched Web of Science, Cochrane Library, Scopus, PubMed, and Embase for randomized controlled trials. Studies evaluating immunotherapy, alternative medicine, or primarily enrolling patients with comorbid asthma were excluded. A frequentist random-effects NMA compared interventions at class and dose-specific levels. Primary outcomes were total nasal symptom score (TNSS), total ocular symptom score, quality of life, and adverse events. Treatment rankings were derived using the surface under the cumulative ranking curve (SUCRA), and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation for Network Meta-Analysis for the TNSS outcome. The protocol was registered in PROSPERO (CRD42024507281). Global and local inconsistencies were evaluated.Results
From 36,669 records, 175 randomized controlled trials (RCTs) encompassing over 90,000 participants were included. In the network meta-analysis, treatment rankings varied across outcomes, and no single regimen consistently outperformed others; the observed heterogeneity and significant inconsistency in several networks precluded firm conclusions regarding comparative effectiveness. Intra-class differences in effect sizes were observed across several drug classes. Certain higher-dose intranasal corticosteroid monotherapies appeared among the top-ranked interventions in SUCRA analyses. Still, these rankings should be interpreted cautiously given the substantial heterogeneity and inconsistency in some networks. The certainty of evidence for the TNSS outcome was moderate to very low in most comparisons.Discussion
Despite sensitivity analyses, significant statistical incoherence persisted in several comparisons, particularly for TNSS in seasonal AR. The analysis was limited to patients without comorbid asthma. Overall, no universally superior regimen could be identified. Given the remaining heterogeneity and inconsistency, the findings should be regarded as exploratory and hypothesis-generating rather than as definitive evidence of comparative effectiveness. These findings raise the possibility that treatment selection may benefit from an individualized approach, although confirmatory studies are needed.Registration
PROSPERO CRD42024507281.