Efficacy of index of reactivity-liquid sublingual immunotherapy in allergic rhinoconjunctivitis: a systematic review and meta-analysis of randomized studies

IntroductionAllergen immunotherapy (AIT) is a well-established treatment with demonstrated efficacy and safety. However, variability in study outcomes remains a challenge, driven by differences in patient characteristics, study designs, and treatment durations. Moreover, disparities in allergen comp...

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Main Authors: Danilo Di Bona, Andrea Di Biase, Giovanni Paoletti, Rosanna Villani, Gaetano Serviddio, Josiane Cognet-Sicé, Silvia Scurati, Giorgio Walter Canonica
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Allergy
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Online Access:https://www.frontiersin.org/articles/10.3389/falgy.2025.1597003/full
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author Danilo Di Bona
Andrea Di Biase
Giovanni Paoletti
Giovanni Paoletti
Rosanna Villani
Gaetano Serviddio
Josiane Cognet-Sicé
Silvia Scurati
Giorgio Walter Canonica
Giorgio Walter Canonica
author_facet Danilo Di Bona
Andrea Di Biase
Giovanni Paoletti
Giovanni Paoletti
Rosanna Villani
Gaetano Serviddio
Josiane Cognet-Sicé
Silvia Scurati
Giorgio Walter Canonica
Giorgio Walter Canonica
author_sort Danilo Di Bona
collection DOAJ
description IntroductionAllergen immunotherapy (AIT) is a well-established treatment with demonstrated efficacy and safety. However, variability in study outcomes remains a challenge, driven by differences in patient characteristics, study designs, and treatment durations. Moreover, disparities in allergen composition and quality of AIT products across manufacturers contribute to significant heterogeneity, complicating the interpretation of efficacy and safety data. This meta-analysis focuses on assessing the efficacy and safety of a single manufacturer’s liquid sublingual immunotherapy (SLIT) for allergic rhinoconjunctivitis (ARC). By narrowing the scope to one specific product, this study seeks to reduce variability linked to product differences, aligning with recommendations from the World Allergy Organization to improve the reliability of meta-analytic findings.MethodsRandomized controlled trials (RCTs) on index of reactivity (IR) SLIT liquid formulations of various allergens were identified through comprehensive searches in electronic databases (MEDLINE, ISI Web of Science, the Cochrane Library, and ClinicalTrial.gov) up to December 2024, complemented by manual searches. Data on populations, treatments, and outcomes were extracted. Efficacy was evaluated by calculating the standardized mean difference (SMD) for symptoms and medication use. Subgroup analyses were performed by age, allergen type and sensitization status. Asthma comorbidity, dose and duration of SLIT were evaluated using meta-regression.ResultsA total of 25 RCTs (1,830 patients) provided data on symptom scores (SS), and 19 RCTs (1,555 patients) reported on medication scores (MS). Analysis revealed that IR-SLIT-liquid was significantly more effective than placebo in reducing both SS (SMD: −0.30; 95% CI: −0.41 to −0.18; P < 0.0001) and MS (SMD: −0.51; 95% CI: −0.72 to −0.29; P < 0.0001). Efficacy outcomes were consistent regardless of factors such as age, allergen type (grass, house dust mites, trees, weeds), sensitization status, asthma presence, or cumulative dose, while longer treatment durations were associated with improved efficacy. No significant adverse events were reported.DiscussionThis meta-analysis underscores the clinical effectiveness and safety of IR-SLIT-liquid, confirming its role as a reliable etiologic treatment for patients with ARC, for all allergens and age groups. The effect size is comparable to other immunotherapy options. The low rates of adverse events and treatment withdrawals highlight favorable tolerability and high level of patient adherence.Systematic Review Registrationhttps://inplasy.com/wp-content/uploads/2025/01/INPLASY-Protocol-7305.pdf, INPLASY 202510049
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publishDate 2025-06-01
publisher Frontiers Media S.A.
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spelling doaj-art-21ea426d01c34412b7ac2446d2144d2e2025-08-20T03:56:49ZengFrontiers Media S.A.Frontiers in Allergy2673-61012025-06-01610.3389/falgy.2025.15970031597003Efficacy of index of reactivity-liquid sublingual immunotherapy in allergic rhinoconjunctivitis: a systematic review and meta-analysis of randomized studiesDanilo Di Bona0Andrea Di Biase1Giovanni Paoletti2Giovanni Paoletti3Rosanna Villani4Gaetano Serviddio5Josiane Cognet-Sicé6Silvia Scurati7Giorgio Walter Canonica8Giorgio Walter Canonica9Department of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, ItalyPersonalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyIntegrated Health Care Department, Stallergenes Greer, Antony, FranceIntegrated Health Care Department, Stallergenes Greer, Antony, FranceDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, ItalyPersonalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, ItalyIntroductionAllergen immunotherapy (AIT) is a well-established treatment with demonstrated efficacy and safety. However, variability in study outcomes remains a challenge, driven by differences in patient characteristics, study designs, and treatment durations. Moreover, disparities in allergen composition and quality of AIT products across manufacturers contribute to significant heterogeneity, complicating the interpretation of efficacy and safety data. This meta-analysis focuses on assessing the efficacy and safety of a single manufacturer’s liquid sublingual immunotherapy (SLIT) for allergic rhinoconjunctivitis (ARC). By narrowing the scope to one specific product, this study seeks to reduce variability linked to product differences, aligning with recommendations from the World Allergy Organization to improve the reliability of meta-analytic findings.MethodsRandomized controlled trials (RCTs) on index of reactivity (IR) SLIT liquid formulations of various allergens were identified through comprehensive searches in electronic databases (MEDLINE, ISI Web of Science, the Cochrane Library, and ClinicalTrial.gov) up to December 2024, complemented by manual searches. Data on populations, treatments, and outcomes were extracted. Efficacy was evaluated by calculating the standardized mean difference (SMD) for symptoms and medication use. Subgroup analyses were performed by age, allergen type and sensitization status. Asthma comorbidity, dose and duration of SLIT were evaluated using meta-regression.ResultsA total of 25 RCTs (1,830 patients) provided data on symptom scores (SS), and 19 RCTs (1,555 patients) reported on medication scores (MS). Analysis revealed that IR-SLIT-liquid was significantly more effective than placebo in reducing both SS (SMD: −0.30; 95% CI: −0.41 to −0.18; P < 0.0001) and MS (SMD: −0.51; 95% CI: −0.72 to −0.29; P < 0.0001). Efficacy outcomes were consistent regardless of factors such as age, allergen type (grass, house dust mites, trees, weeds), sensitization status, asthma presence, or cumulative dose, while longer treatment durations were associated with improved efficacy. No significant adverse events were reported.DiscussionThis meta-analysis underscores the clinical effectiveness and safety of IR-SLIT-liquid, confirming its role as a reliable etiologic treatment for patients with ARC, for all allergens and age groups. The effect size is comparable to other immunotherapy options. The low rates of adverse events and treatment withdrawals highlight favorable tolerability and high level of patient adherence.Systematic Review Registrationhttps://inplasy.com/wp-content/uploads/2025/01/INPLASY-Protocol-7305.pdf, INPLASY 202510049https://www.frontiersin.org/articles/10.3389/falgy.2025.1597003/fullmeta-analysisrandomized controlled trialrhinitisallergicSLIT-liquidsublingual immunotherapy
spellingShingle Danilo Di Bona
Andrea Di Biase
Giovanni Paoletti
Giovanni Paoletti
Rosanna Villani
Gaetano Serviddio
Josiane Cognet-Sicé
Silvia Scurati
Giorgio Walter Canonica
Giorgio Walter Canonica
Efficacy of index of reactivity-liquid sublingual immunotherapy in allergic rhinoconjunctivitis: a systematic review and meta-analysis of randomized studies
Frontiers in Allergy
meta-analysis
randomized controlled trial
rhinitis
allergic
SLIT-liquid
sublingual immunotherapy
title Efficacy of index of reactivity-liquid sublingual immunotherapy in allergic rhinoconjunctivitis: a systematic review and meta-analysis of randomized studies
title_full Efficacy of index of reactivity-liquid sublingual immunotherapy in allergic rhinoconjunctivitis: a systematic review and meta-analysis of randomized studies
title_fullStr Efficacy of index of reactivity-liquid sublingual immunotherapy in allergic rhinoconjunctivitis: a systematic review and meta-analysis of randomized studies
title_full_unstemmed Efficacy of index of reactivity-liquid sublingual immunotherapy in allergic rhinoconjunctivitis: a systematic review and meta-analysis of randomized studies
title_short Efficacy of index of reactivity-liquid sublingual immunotherapy in allergic rhinoconjunctivitis: a systematic review and meta-analysis of randomized studies
title_sort efficacy of index of reactivity liquid sublingual immunotherapy in allergic rhinoconjunctivitis a systematic review and meta analysis of randomized studies
topic meta-analysis
randomized controlled trial
rhinitis
allergic
SLIT-liquid
sublingual immunotherapy
url https://www.frontiersin.org/articles/10.3389/falgy.2025.1597003/full
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