Clinical Evaluation of Allergen Immunotherapy for Allergic Asthma

Francesco Catamerò,1,2 Simone Foti Randazzese,3 Davide Caimmi,4,5 Giovanni Paoletti,6,7 Giorgio Walter Canonica,6,7 Enrico Heffler,6,7 Andrea Giovanni Ledda,8 Stefano Del Giacco,8 Giulia Anna Maria Luigia Costanzo,8 Giuseppe Guida,9,10 Fabio Luigi Massimo Ricciardolo,9– 11 Francesca Bertolini,9 Remo Poto,12 Rory Chan,13 Gilda Varricchi,12,14 Mattia Giovannini1,21Department of Health Sciences, University of Florence, Florence, Italy; 2Allergy Unit, Meyer Children’s Hospital IRCCS, Florence, Italy; 3Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy; 4Allergy Unit, Hôpital Arnaud De Villeneuve, University Hospital of Montpellier, Montpellier, Occitanie, France; 5IDESP, UMR 1318, University of Montpellier - INSERM, Montpellier, Occitanie, France; 6Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; 7Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 8Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy; 9Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; 10Severe Asthma, Rare Lung Disease and Respiratory Pathophysiology Unit, San Luigi Gonzaga University Hospital, Orbassano, Italy; 11Institute of Translational Pharmacology, National Research Council (IFT-CNR), Palermo, Italy; 12Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy; 13University of Dundee, School of Medicine, Dundee, UK; 14Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, ItalyCorrespondence: Francesco Catamerò, Department of Health Sciences, University of Florence, Viale Pieraccini 24, Florence, 50139, Italy, Email francesco.catamero@unifi.itAbstract: Allergen immunotherapy (AIT) is the only available disease-modifying treatment for IgE-mediated allergic disease. Unlike conventional pharmacotherapy, AIT targets the underlying immune dysregulation driving allergic asthma (AA), with the potential to induce sustained off-treatment benefits. This narrative review examines the available evidence from both randomized controlled trials (RCTs) and real-world evidence to provide an updated and balanced overview of the clinical role of AIT in AA across different age groups. RCTs indicate that AIT can improve asthma symptom scores, reduce medication requirements and exacerbation risk, with additional steroid-sparing effects; however, findings are not consistent across trials. The strongest evidence is confined to house dust mite SLIT tablets, and the most recent Cochrane review judged the evidence insufficient for firm conclusions. Observational database studies enrolling up to 445,000 patients are consistent with these findings, reporting reductions in asthma events, medication use and treatment step-up, although their design precludes causal inference. Beyond symptomatic control, AIT has demonstrated a preventive role by interrupting the allergic trajectory, reducing the risk of new-onset asthma in patients with allergic rhinitis, and slowing progression to more severe asthma phenotypes. Long-term follow-up studies, mostly small and open in design, suggest that benefit may persist for up to 15 years after AIT discontinuation. Preliminary uncontrolled evidence also suggests that AIT may be feasible in selected patients with well-controlled severe asthma. In conclusion, AIT represents a uniquely positioned, disease-modifying strategy in the management of AA, with potential benefits spanning symptom control, prevention of disease onset and progression, and long-term benefits persisting after treatment discontinuation.Keywords: allergen immunotherapy, allergic asthma, SLIT, SCIT, disease-modifying, asthma prevention