Efficacy of house dust mite allergen immunotherapy in allergic rhinitis: a network meta-analysis based on component-resolved classification.

BACKGROUND: House dust mite allergen immunotherapy (HDM-AIT) trials in allergic rhinitis show substantial efficacy heterogeneity, traditionally evaluated by administration route. Whether clinical efficacy differs among HDM-AIT preparations with different allergen compositional breadth remains unclear. OBJECTIVE: To compare HDM-AIT efficacy using a component-resolved framework that stratifies preparations by allergen compositional breadth. METHODS: We searched PubMed, Embase, and CENTRAL for double-blind, placebo-controlled randomized trials of HDM-AIT lasting at least 12 months. Interventions were classified as comprehensive-component subcutaneous immunotherapy (CC-SCIT), major-component-dominant subcutaneous immunotherapy (MCD-SCIT), or major-component-dominant sublingual immunotherapy tablet (MCD-SLIT-tablet) using a prespecified component-resolved framework in which the breadth of treatment-induced component-specific IgG4 responses served as the primary node-defining criterion, with component-specific IgG and proteomic evidence used as supportive evidence. Frequentist pairwise and Bayesian network meta-analyses were performed. The primary outcome was symptom score; secondary outcomes were medication score and combined symptom and medication score. RESULTS: Sixteen trials involving 7,329 participants were included. For symptom score, CC-SCIT showed the most favorable estimated treatment effect versus placebo (standardized mean difference [SMD], -0.40; 95% credible interval [CrI], -0.73 to -0.11; surface under the cumulative ranking curve [SUCRA], 82.6%), while MCD-SLIT-tablet showed a more precise estimate supported by a larger evidence base (SMD, -0.30; 95% CrI, -0.41 to -0.20; SUCRA, 60.7%). For medication score, CC-SCIT (SMD, -0.40; 95% CrI, -0.81 to 0.00; SUCRA, 79.8%) and MCD-SCIT (SMD, -0.38; 95% CrI, -0.72 to -0.05; SUCRA, 78.5%) showed similar estimated effects, whereas MCD-SLIT-tablet showed a smaller but more precise effect (SMD, -0.15; 95% CrI, -0.28 to 0.00; SUCRA, 39.9%). For combined symptom and medication score, CC-SCIT showed the largest estimated effect versus placebo (SMD, -0.84; 95% CrI, -1.53 to -0.37; SUCRA, 99.5%). The network was star-shaped, and comparisons among non-placebo treatment nodes were indirect. Posterior rank distributions also indicated uncertainty in the relative ordering of the treatment nodes, particularly those supported by fewer trials. CONCLUSION: Reported immunologic and compositional profiles of HDM-AIT preparations were associated with variability in trial-level efficacy estimates. These findings support product-level molecular characterization and direct comparative studies as priorities for future precision AIT. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/, CRD420261307571.