Comprehensive-component subcutaneous immunotherapy shows the most favorable symptom score reduction in allergic rhinitisComprehensive Immunotherapy Shows Best Results for Allergic Rhinitis Symptoms

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. To compare HDM-AIT efficacy using a component-resolved framework that stratifies preparations by allergen compositional breadth. 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. 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. 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. https://www.crd.york.ac.uk/PROSPERO/view/, CRD420261307571.