Pulmonology
COPD
The Management of Refractory Chronic Obstructive Pulmonary Disease
Patients with refractory chronic obstructive pulmonary disease (COPD) experience unmet treatment needs despite receiving standard-of-care maintenance therapy. Presenters at the recent CHEST 2026 Annual Meeting shared data on currently US Food and Drug Administration (FDA)–approved therapies and emerging treatment options for these patients.
Following these presentations, featured expert Frank C. Sciurba, MD, FCCP, was interviewed by Conference Reporter Associate Editor-in-Chief Mona Shah, PharmD. Clinical perspectives from Dr Sciurba on these findings are presented here.
When we discuss refractory COPD, we need to start by establishing appropriate maintenance management followed by identifying patients who remain symptomatic and have ongoing treatment needs. Because COPD is incompletely reversible, we are constantly trying to chip away at the dysfunction, poor quality of life, symptoms, and exertional intolerance and instability resulting in exacerbations that these patients experience.
Basic maintenance should include the use of long-acting bronchodilator therapy. In general, this means treatment with dual therapy with a LAMA and a LABA, with or without ICS. The use of ICS can be guided by patients’ exacerbation frequencies and blood eosinophil levels. Patients with COPD who experience 2 or more moderate exacerbations in the past year and have blood eosinophil levels of 300 cells/µL or higher are more likely to be responsive to the addition of ICS. For patients with at least 1 moderate exacerbation in the past year and blood eosinophil levels that fall between approximately 100 and 300 cells/µL, ICS can also be considered. Those with blood eosinophil levels below 100 cells/µL who are symptomatic but do not have frequent exacerbations are appropriate candidates for dual bronchodilator treatment without ICS. It is also important to ensure that patients are up to date on their vaccinations. Supplemental oxygen therapy may be appropriate with exertion and also at rest if patients need it. Finally, pulmonary rehabilitation is very important to optimize function in these individuals.
Despite maintenance treatment, patients with COPD can continue to be symptomatic with profound exertional dyspnea with or without exacerbations, and they may have frequent exacerbations. Most patients who have frequent exacerbations experience some degree of symptoms, even on their good days. It is unusual for any of these patients to be generally asymptomatic. In fact, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 report states that if a patient has had just 1 exacerbation requiring ICS in the past year, they are considered to have high-risk frequent exacerbations, and they have unmet treatment needs. There are also patients who have profound symptoms—especially dyspnea—but do not experience frequent exacerbations. Device therapies can be supportive for these individuals, including endobronchial valves and other new research techniques for patients with emphysema or hyperinflation symptoms. However, the biggest updates from CHEST 2026 in addressing unmet needs for patients with refractory COPD were focused on biologic therapies.
FDA-approved biologic therapies for patients with COPD with an eosinophilic phenotype who are on triple therapy and continue to exacerbate include dupilumab and mepolizumab. Data presented from multiple studies at CHEST 2026 by me and my colleagues Stefanie Kolterer, PhD, Mena Soliman, MD, MSc, Gerard J. Criner, MD, FACP, FACCP, Nicola A. Hanania, MD, MS, FCCP, Mishal Tariq, MBBS, Shafaq Jabeen, MBBS, and Reynold A. Panettieri Jr, MD, continue to confirm the roles of dupilumab and mepolizumab in managing refractory COPD.
Historically, we knew that patients with blood eosinophil levels of 300 cells/µL or higher were appropriate candidates for dupilumab and mepolizumab. However, we now understand that blood eosinophil levels can vary over time and that we can also consider these therapies in patients with blood eosinophil levels below 150 cells/µL who have historically had elevated levels. Previously mentioned data presented at the meeting by Dr Soliman, Dr Hanania, and me suggest that patients with COPD with type 2 inflammation may be responsive to or stabilized by dupilumab and mepolizumab.
Also at CHEST 2026, Navneet Gupta, MBBS, presented data on ensifentrine, a first-in-class, inhaled, dual PDE3/PDE4 inhibitor, small-molecule drug that is FDA approved for the maintenance treatment of COPD, which is also being studied as an add-on to triple therapy to reduce COPD exacerbations.
Finally, as for the emerging treatment options for refractory COPD discussed at CHEST 2026, my colleagues George Washko, MD, MS, Henrik Watz, MD, PhD, and I presented data from multiple studies on tozorakimab, an exciting, investigational, first-in-class biologic agent that targets IL-33. The data suggest that this agent is effective in individuals with both low and elevated eosinophil counts.
Patients with refractory COPD are continuing to suffer. I think that the progress being made with the currently FDA-approved treatment options is exciting. They are helping many patients, but unmet needs in COPD remain, and we need to continue studying new therapies.
Anzueto AR, Bon J, Shah S, Biswas A, Gould S, Min J. Mepolizumab improves health-related quality of life in COPD regardless of smoking status: pooled results from phase 3 randomized trials [poster 4368] [session: Obstructive lung diseases scientific abstract posters (F): COPD]. Poster presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Bhatt SP, Brusselle GG, Puggioni F, et al. Effect of dupilumab on quality of life mediated by exacerbation reduction, lung function improvements, or decline in fractional exhaled nitric oxide: BOREAS and NOTUS [session: Precision COPD: type 2 inflammation, biomarkers, and targeted therapy]. Abstract presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Criner GJ, Wilkinson T, Sciurba FC, et al. Dupilumab reduces exacerbations across all seasons in patients with COPD [poster 4371] [session: Obstructive lung diseases scientific abstract posters (F): COPD]. Poster presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2026 report. Accessed October 27, 2026. https://goldcopd.org/wp-content/uploads/2026/01/GOLD-REPORT-2026-v1.3-8Dec2025_WMV2.pdf
Gupta N, Le JP, Malode A, et al. Real-world effectiveness of adjunctive ensifentrine in COPD patients receiving inhaled triple therapy: a propensity-matched US cohort study [session: Reframing COPD: phenotypes, outcomes, therapeutics, and the future of care delivery]. Abstract presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Hanania NA, Kraft M, Burrows E, Biswas A, Gould S, Min J. Mepolizumab reduces systemic corticosteroid utilization in COPD with type 2 inflammation: pooled results from phase 3 randomized trials [session: Precision COPD: type 2 inflammation, biomarkers, and targeted therapy]. Abstract presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Janssens W, Brusselle GG, Bhutani M, et al. Exacerbation dynamics in COPD with type 2 inflammation: change-point Time-T analysis of early vs sustained effects in BOREAS and NOTUS [session: COPD in a flash: high-yield insights for practice]. Abstract presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Mahapatra SS, Ramesh S, Tariq M, et al. Comparative efficacy and safety of biologic therapies in eosinophilic COPD: a systematic review and network meta-analysis [session: Obstructive lung diseases and their mimics]. Abstract presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Mohamed AA, Shehata A, Al Ghnaimat A, et al. Efficacy and safety of mepolizumab in COPD with eosinophilic phenotype: a systematic review and meta-analysis of randomized controlled trials [session: Reframing COPD: phenotypes, outcomes, therapeutics, and the future of care delivery]. Abstract presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Panettieri RA, Paczkowski R, Mei H, et al. The real-world clinical profile of mepolizumab initiators following Food and Drug Administration approval for chronic obstructive pulmonary disease [poster 3206] [session: Late-breaking scientific abstract posters (A): allergy and airway, obstructive lung diseases, pharmacotherapeutics]. Poster presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Sciurba FC, Bhatt SP, Watz H, et al. Tozorakimab treatment improves daily respiratory symptoms in patients with chronic obstructive pulmonary disease: results from the OBERON and TITANIA studies [session: Top late-breaking abstracts: new drugs, new targets, new tools]. Abstract presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Sciurba FC, Bon J, Burrows E, Biswas A, Gould S, Min J. Mepolizumab improves health-related quality of life in COPD irrespective of dyspnea severity: pooled results from phase 3 randomized trials [session: Precision COPD: type 2 inflammation, biomarkers, and targeted therapy]. Abstract presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Washko G, Sciurba FC, Watz H, et al. Tozorakimab leads to long-term reductions in the number of lung segments with mucus plugs in patients with COPD: results from the phase 3 PROSPERO extension study [session: Top late-breaking abstracts: new trial data from bench to bronchoscope]. Abstract presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
Watz H, Sciurba FC, Bourdin A, et al. Long-term efficacy and safety of tozorakimab in patients with COPD: an integrated analysis of OBERON, TITANIA and the PROSPERO extension study [poster 3204] [session: Late-breaking scientific abstract posters (A): allergy and airway, obstructive lung diseases, pharmacotherapeutics]. Poster presented at: American College of Chest Physicians 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.
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