Biologic Use in Type 2 versus Non-Type 2 Asthma: Similarities, Differences, and Challenges.
- 1Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.
- 2Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
- 3Pulmonology Clinic, Department of Pneumology and Oncology, "Ospedale dei Colli", Naples, Italy.
Abstract
Biologic therapy has transformed the management of severe asthma, but its benefit has been distributed unevenly. Six monoclonal antibodies are licensed (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab), joined most recently by the ultra-long-acting anti-interleukin (IL)-5 antibody depemokimab. All were developed within, and are prescribed on the basis of, the type 2 (T2) inflammatory pathway. Patients whose disease is driven by IL-4, IL-13, IL-5 and IgE now have several effective options; patients whose disease is not have almost none. This asymmetry is the central problem in severe asthma today, and it is the subject of this review. In this narrative review, informed by a structured literature search, we synthesize evidence from randomized controlled trials of every approved biologic, from real-world data and from the substantial body of negative trials in non-T2 disease. We argue that the T2/non-T2 dichotomy is operationally useful but biologically misleading: its thresholds are arbitrary and unstable under corticosteroid exposure, low T2 biomarkers are not synonymous with absent T2 biology, and non-T2 disease is itself heterogeneous. We examine what the phenotypes share (epithelial alarmin signaling, airway remodeling, corticosteroid-related morbidity and the treatable-traits paradigm) and where they differ. We then address the practical challenges of clinical decision-making: selecting a first biologic when eligibility criteria overlap, managing partial response, switching, de-escalation and clinical remission. Finally, we evaluate agents in development, including anti-TSLP receptor antibodies, IL-33/ST2 blockade, bispecific constructs, OX40L-directed therapy and oral eosinophil-depleting small molecules, and outline the trial designs and biomarkers that will be needed if patients with non-T2 disease are to be served as well as those with T2 disease.
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BibTeX
@article{maglio2026biologic,
title = {{Biologic Use in Type 2 versus Non-Type 2 Asthma: Similarities, Differences, and Challenges.}},
author = {Angelantonio Maglio and Luisa Oriana D'Auria and Antonio Franzese and Maria Elena Liguori and Sara Gramazio and Giuseppe Arnone and Valeria Longobardi and Corrado Pelaia and Girolamo Pelaia and Cecilia Calabrese and Carolina Vitale and Alessandro Vatrella},
journal = {Journal of inflammation research},
year = {2026},
month = oct,
doi = {10.2147/jir.s589946},
url = {https://europepmc.org/article/MED/42899165},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Biologic Use in Type 2 versus Non-Type 2 Asthma: Similarities, Differences, and Challenges.
AU - Angelantonio Maglio
AU - Luisa Oriana D'Auria
AU - Antonio Franzese
AU - Maria Elena Liguori
AU - Sara Gramazio
AU - Giuseppe Arnone
AU - Valeria Longobardi
AU - Corrado Pelaia
AU - Girolamo Pelaia
AU - Cecilia Calabrese
AU - Carolina Vitale
AU - Alessandro Vatrella
PY - 2026
DA - 2026/10/15
JO - Journal of inflammation research
DO - 10.2147/jir.s589946
UR - https://europepmc.org/article/MED/42899165
AB - Biologic therapy has transformed the management of severe asthma, but its benefit has been distributed unevenly. Six monoclonal antibodies are licensed (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab), joined most recently by the ultra-long-acting anti-interleukin (IL)-5 antibody depemokimab. All were developed within, and are prescribed on the basis of, the type 2 (T2) inflammatory pathway. Patients whose disease is driven by IL-4, IL-13, IL-5 and IgE now have several effective options; patients whose disease is not have almost none. This asymmetry is the central problem in severe asthma today, and it is the subject of this review. In this narrative review, informed by a structured literature search, we synthesize evidence from randomized controlled trials of every approved biologic, from real-world data and from the substantial body of negative trials in non-T2 disease. We argue that the T2/non-T2 dichotomy is operationally useful but biologically misleading: its thresholds are arbitrary and unstable under corticosteroid exposure, low T2 biomarkers are not synonymous with absent T2 biology, and non-T2 disease is itself heterogeneous. We examine what the phenotypes share (epithelial alarmin signaling, airway remodeling, corticosteroid-related morbidity and the treatable-traits paradigm) and where they differ. We then address the practical challenges of clinical decision-making: selecting a first biologic when eligibility criteria overlap, managing partial response, switching, de-escalation and clinical remission. Finally, we evaluate agents in development, including anti-TSLP receptor antibodies, IL-33/ST2 blockade, bispecific constructs, OX40L-directed therapy and oral eosinophil-depleting small molecules, and outline the trial designs and biomarkers that will be needed if patients with non-T2 disease are to be served as well as those with T2 disease.
SN - 1178-7031
ER -