IR (index of reactivity)-house dust mite sublingual immunotherapy liquid formulation for allergic rhinoconjunctivitis: Systematic review and meta-analysis of randomized and nonrandomized studies

Danilo Di Bona; Palma Carlucci; Federico Spataro; Giovanni Paoletti; Josiane Cognet-Sicé; Silvia Scurati; Giorgio Walter Canonica

doi:10.1016/j.jacig.2024.100208

IR (index of reactivity)-house dust mite sublingual immunotherapy liquid formulation for allergic rhinoconjunctivitis: Systematic review and meta-analysis of randomized and nonrandomized studies

J Allergy Clin Immunol Glob. 2024 Jan 9;3(2):100208. doi: 10.1016/j.jacig.2024.100208. eCollection 2024 May.

Authors

Danilo Di Bona¹, Palma Carlucci¹, Federico Spataro¹, Giovanni Paoletti^{2

3}, Josiane Cognet-Sicé⁴, Silvia Scurati⁴, Giorgio Walter Canonica^{2

3}

Affiliations

¹ Department of Precision and Regenerative Medicine and Jonic Area, Unit of Allergology, University of Bari Aldo Moro, Bari, Italy.
² Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy.
³ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
⁴ Stallergenes Greer, Antony, France.

Abstract

Background: Although randomized controlled trials (RCT) are the reference standard of evidence in allergen immunotherapy (AIT), nonrandomized studies (NRS) are needed to confirm their results in more representative populations, particularly for treatment duration and persistence. However, when discrepancies are observed between RCT and NRS, NRS reliability decreases because these discrepant results are generally attributed to the methodologic flaws of NRS.

Objective: We compared the benefit of sublingual AIT (SLIT) for allergic rhinoconjunctivitis in NRS versus RCT focusing on a single product/allergen to reduce heterogeneity.

Methods: For meta-analysis, house dust mite (HDM) SLIT liquid formulation studies were sourced from computerized (Medline, Web of Science, and LILACS databases, to January 2023) and manual literature searches. Populations, treatments, and outcome data were combined (DerSimonian-Laird method). Noncomparative NRS were compared to RCT' SLIT arm before and after treatment. Efficacy was determined as the standardized mean difference (SMD) in symptom score (SS) and medication score (MS).

Results: Data from 12 NRS (682 patients) and 8 RCT (176 patients) were analyzed. The benefit with index of reactivity (IR)-HDM SLIT liquid formulation was found significant for, first, SS in both NRS (SMD = -1.27; 95% confidence interval [CI], -1.64, -0.90) and RCT (SMD = -0.56; 95% CI, -0.90, -0.21), and second, MS with SMD equal to -1.35 (95% CI, -1.77, -0.93) and -0.46 (95% CI, -0.67, -0.25), respectively. Metaregression showed that symptom improvement was correlated with treatment duration with consistent results in NRS and RCT with 12-month SS data: -0.87 (interquartile range, -1.02, -0.77) and -0.75 (interquartile range, -0.93, -0.41), respectively.

Conclusion: This meta-analysis showed comparable clinical benefit of IR-HDM SLIT liquid formulation increasing over time in both NRS and RCT, suggesting that NRS may reliably integrate RCT results and be considered for guidelines.

Keywords: Guidelines; nonrandomized studies; randomized controlled trials; real-life; rhinoconjunctivitis; study quality; sublingual immunotherapy.