COPD: real-world evidence on single-inhaler triple therapy and the emergence of biologic therapy
12 affiliations
- 1Department of Medical, Surgical and Health Sciences, University of Trieste
- 2Department of Pulmonology, Santa Maria Degli Angeli Hospital
- 3Department of Pulmonary Rehabilitation, Azienda Sanitaria Universitaria Friuli Centrale
- 4Department of Pneumology, Ruhrlandklinik, University Hospital Essen, University of Duisburg-Essen
- 5Rheumatology Unit, ASST Ovest Milanese, Legnano Hospital
- 6Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, the University of Manchester, Manchester Academic Health Science Centre
- 7Department of Rheumatology, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation
- 8NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust
- 9Department of Experimental and Clinical Medicine, Division of Internal Medicine, Azienda Ospedaliera Universitaria Careggi, University of Florence
- 10Department of Rheumatology and Immunology, Shantou Central Hospital
- 11Department of Pulmonology, University Hospital of Cattinara
- 12Department of Cardiac, Respiratory Medicine, Thoracic, Vascular Sciences and Public Health, University of Padova
Abstract
Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide. Despite major pharmacological advances, a substantial gap persists between guideline recommendations and routine clinical practice, particularly after exacerbations. This narrative review summarizes current evidence supporting personalized pharmacological escalation in COPD, focusing on single-inhaler triple therapy (SITT) and the emergence of biologic therapy. SITT, combining an inhaled corticosteroid, a long-acting β ₂ -agonist and a long-acting muscarinic antagonist, is now the preferred inhaled strategy for patients requiring ICS-containing triple therapy. Real-world studies indicate that, compared with multiple-inhaler triple therapy, SITT is associated with better adherence and persistence, lower exacerbation rates and improved clinical outcomes, although observational findings require cautious causal interpretation. In parallel, COPD has entered the era of targeted biologic therapy. Dupilumab was the first biologic approved for COPD, following the BOREAS and NOTUS trials in patients with chronic bronchitis, blood eosinophils ≥300 cells/µL and persistent exacerbations despite triple therapy. Mepolizumab has more recently provided robust phase 3 evidence in eosinophilic COPD through the MATINEE trial. Early real-world dupilumab studies further suggest potential effectiveness in selected patients under-represented in pivotal trials, including those with advanced age, severe airflow limitation, oxygen dependence or high mucus burden. Beyond canonical type 2 pathways, IL-33 inhibition with tozorakimab may further broaden targeted treatment to COPD phenotypes without a clear eosinophilic signature. Integrating these advances within a treatable-traits framework may help optimize patient selection, close post-exacerbation therapeutic gaps, and align pharmacological escalation with comorbidity management, adherence, inhaler technique and rehabilitation needs.
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BibTeX
@article{re2026copd,
title = {{COPD: real-world evidence on single-inhaler triple therapy and the emergence of biologic therapy}},
author = {Beatrice Da Re and Nicolò Reccardini and Giorgio Monteleone and Eugenio Capparelli and Michael Hughes and Giulia Bandini and Yukai Wang and Paola Confalonieri and Francesco Salton and Marco Confalonieri and Umberto Semenzato and Barbara Ruaro},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1983112},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1983112/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - COPD: real-world evidence on single-inhaler triple therapy and the emergence of biologic therapy
AU - Beatrice Da Re
AU - Nicolò Reccardini
AU - Giorgio Monteleone
AU - Eugenio Capparelli
AU - Michael Hughes
AU - Giulia Bandini
AU - Yukai Wang
AU - Paola Confalonieri
AU - Francesco Salton
AU - Marco Confalonieri
AU - Umberto Semenzato
AU - Barbara Ruaro
PY - 2026
DA - 2026/10/23
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1983112
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1983112/full
AB - Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide. Despite major pharmacological advances, a substantial gap persists between guideline recommendations and routine clinical practice, particularly after exacerbations. This narrative review summarizes current evidence supporting personalized pharmacological escalation in COPD, focusing on single-inhaler triple therapy (SITT) and the emergence of biologic therapy. SITT, combining an inhaled corticosteroid, a long-acting β ₂ -agonist and a long-acting muscarinic antagonist, is now the preferred inhaled strategy for patients requiring ICS-containing triple therapy. Real-world studies indicate that, compared with multiple-inhaler triple therapy, SITT is associated with better adherence and persistence, lower exacerbation rates and improved clinical outcomes, although observational findings require cautious causal interpretation. In parallel, COPD has entered the era of targeted biologic therapy. Dupilumab was the first biologic approved for COPD, following the BOREAS and NOTUS trials in patients with chronic bronchitis, blood eosinophils ≥300 cells/µL and persistent exacerbations despite triple therapy. Mepolizumab has more recently provided robust phase 3 evidence in eosinophilic COPD through the MATINEE trial. Early real-world dupilumab studies further suggest potential effectiveness in selected patients under-represented in pivotal trials, including those with advanced age, severe airflow limitation, oxygen dependence or high mucus burden. Beyond canonical type 2 pathways, IL-33 inhibition with tozorakimab may further broaden targeted treatment to COPD phenotypes without a clear eosinophilic signature. Integrating these advances within a treatable-traits framework may help optimize patient selection, close post-exacerbation therapeutic gaps, and align pharmacological escalation with comorbidity management, adherence, inhaler technique and rehabilitation needs.
SN - 1663-9812
ER -