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

Paoletti G, Valli N, Di Bona D et al. (2026) Front. Allergy 7:1940709. doi: 10.3389/falgy.2026.1940709

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. 

Schematic overview of the effects of SLIT on allergic disease.
Evidence from randomized controlled trials and real-world studies
indicates reduced symptoms and medication use in allergic rhinitis,
 improved quality of life, and increased IgG4, secretory IgA (sIgA)/
IgE-blocking activity.
In asthma, SLIT is associated with fewer exacerbations and reduced
use of asthma medications. Sustained clinical benefits after treatment
 discontinuation have been demonstrated in both adults and children,
with evidence reported for pollen and house dust mite allergens.
Created with BioRender.com.

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.

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