Sublingual allergen immunotherapy: evidence from randomized trials, real-world studies and meta-analyses.

Abstract

Background: Allergen immunotherapy is the only potentially disease-modifying treatment for IgE-mediated respiratory allergy. Among the available routes, sublingual immunotherapy (SLIT) has gained prominence because of its favorable safety profile and greater patient acceptability.

Objectives: This narrative review critically appraises the clinical efficacy, real-world effectiveness, and long-term disease-modifying potential of SLIT for seasonal and perennial respiratory allergies by integrating evidence from randomized controlled trials, large observational cohorts, and meta-analyses, with attention to allergen- and product-specific outcomes and age-related differences.

Results: Robust RCT evidence supports clinically meaningful reductions in symptoms and medication use with grass and HDM SLIT tablets, with sustained benefits observed up to 1-2 years after a 3-year treatment course in key trials. Real-world cohorts corroborate these findings and additionally report a reduced risk of new asthma onset and lower long-term medication dispensing after SLIT. Evidence for SLIT in asthma shows reductions in exacerbation risk in some trials, although its effects on day-to-day control are less consistent. Pediatric trials generally mirror adult outcomes, with favorable safety and efficacy, particularly for standardized tablets; however, heterogeneity across trials and historical methodological limitations remain important caveats. Meta-analyses confirm overall efficacy but highlight substantial between-study heterogeneity and the importance of product-specific evaluations.

Conclusions: SLIT could be an effective, well-tolerated, disease-modifying option for respiratory allergic rhinitis and shows promise for selected asthma outcomes. Optimal benefits require standardized, adequately dosed formulations and sustained adherence (≥3 years). Future research should prioritize product-specific, adequately powered trials with standardized outcomes to refine patient selection and long-term disease-modification endpoints.