D3.194 - Carry-Over Effect of House Dust Mite (HDM) Immunotherapy for Allergic Respiratory Conditions in Pediatric and Adolescent Populations: A Systematic Review and Narrative Synthesis

Allergic respiratory diseases, such as allergic rhinitis and asthma, often begin in childhood and represent a major global health burden. They are closely linked to early-life sensitization to perennial indoor allergens, particularly house dust mite (HDM). Although pharmacological therapies provide symptomatic relief, they do not modify disease progression. Allergen immunotherapy (AIT) is the only disease-modifying treatment, but the persistence of clinical benefits after discontinuation remains unclear in pediatric populations. This review examines the long-term, post-treatment (carry-over) effects of HDM immunotherapy in children and adolescents.

This review followed MECIR standards and was reported according to PRISMA 2020. Randomized controlled trials and cohort studies enrolling children and adolescents (5–17 years) with house dust mite (HDM)–related allergic respiratory diseases were eligible if they evaluated subcutaneous or sublingual HDM immunotherapy for at least three years, with a minimum of one year of post-treatment follow-up. Primary outcomes were long-term symptom control and medication use after treatment discontinuation, with quality of life as a secondary outcome. Searches were conducted in MEDLINE, CENTRAL, Scopus, ClinicalTrials.gov, and ICTRP through October 2025, supplemented by reference screening and author contact. Two reviewers independently conducted study selection, data extraction, and risk-of-bias assessment using Covidence. Risk of bias was assessed with RoB 2 and ROBINS-I-V2, findings were synthesized narratively due to heterogeneity, and certainty of evidence was evaluated using GRADE.

Six studies (one randomized controlled trial and five cohort studies) evaluating house dust mite (HDM) immunotherapy in children and adolescents were included. Across symptom-, medication-, combined symptom–medication, and quality-of-life domains, HDM immunotherapy consistently favored improved long-term clinical outcomes compared with control, with benefits persisting up to six years after treatment discontinuation. Evidence from the single RCT demonstrated sustained reductions in symptoms and medication use, while cohort studies reported substantial symptom remission and marked reductions in pharmacotherapy. However, certainty of evidence ranged from moderate to very low. All included studies were judged at high risk of bias, driven by confounding, lack of blinding, incomplete outcome reporting, and reliance on non-randomized designs. Consequently, observed long-term benefits should be interpreted cautiously.

All included studies consistently favored house dust mite (HDM) immunotherapy, demonstrating sustained improvements in symptoms, medication use, and quality of life after treatment discontinuation. These carry-over effects are biologically plausible, reflecting established immunological mechanisms of allergen immunotherapy that require prolonged exposure to stabilize immune tolerance. However, all studies were at high risk of bias and overall certainty of evidence was low, underscoring the need for well-designed pediatric randomized trials with standardized outcomes and long-term follow-up.