2025 GOLD Report for COPD: MeiLan Han, MD, MS, Discusses Addition of Dupilumab, Ensifentrine

MeiLai K Han, MD, MS

Updates to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report for 2025 in part reflect the growing trend in precision medicine, which is being driven by more refined understanding of disease pathophysiology. In a recent interview with Patient Care, MeiLan Han, MD, MS, a member of the GOLD science committee and professor of internal medicine and chief of the division of pulmonary and critical care medicine at the University of Michigan Health, clarified the report's division in to 2 sections with separate algorithms for initial therapy and follow-up therapy. The most important update to the latter algorithm is the inclusion of 2 therapies approved by the FDA in 2024 to further reduce symptoms and disease exacerbations. Han explains more in the following transcript which has been edited for length and clarity.

Patient Care: Were there updates made to the guidelines that reflect the growing understanding of the heterogeneity of COPD, ie, disease phenotypes?

Absolutely. I think this is where we’re seeing the biggest changes in COPD management. First it's important to point out a clarification in the 2025 GOLD report. An area that often causes confusion is that the GOLD report divides treatment into 2 phases: initial therapy and follow-up therapy. After starting a patient on a treatment, you move away from the initial guidelines and focus on follow-up recommendations.

A notable change this year is that the combination of inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) has been removed from the initial management phase. This shift surprised many physicians, especially since many primary care patients are still on this combination. The updated GOLD guidelines include a section addressing what to do if a patient is already on ICS/LABA. If they’re stable, that’s fine, but there’s now guidance for moving forward.

The most significant updates this year involve two new FDA-approved medications for COPD: ensifentrine and dupilumab, both added to the follow-up therapy section.

For follow-up therapy, GOLD now emphasizes tailoring treatment based on the patient’s primary issue: symptoms like shortness of breath versus exacerbations. Ensifentrine is categorized under the shortness-of-breath pathway. It’s a nebulized PDE3/PDE4 inhibitor designed as an add-on to existing inhalers. There is phase3 data showing improvements in lung function and symptoms, with some reduction in exacerbations. However, GOLD placed ensifentrine in the symptom management category because most participants in the phase 3 study were not on triple inhaled therapy—considered the current standard of care—making it difficult to interpret its impact on exacerbations.

The second addition to the follow-up section, dupilumab, reflects the shift toward precision medicine, focusing more on COPD phenotypes. Dupilumab specifically targets the IL-4 and IL-13 pathways, which are associated with type 2 inflammation. While this pathway is more commonly linked to asthma, we now recognize it in COPD patients with elevated eosinophil counts (≥300 cells/μL). In these patients, dupilumab has shown significant reductions in exacerbations, even for those already on triple inhaled therapy.

So, the 2025 GOLD update provides a few options for a patient who continues to experience COPD exacerbations. You can use azithromycin as add-on therapy, particularly for patients who are non-smokers; you can add roflumilast if chronic bronchitis is the primary symptom; and now, dupilumab is a recommended option for patients with high eosinophil counts. Overall, we are talking about more targeted, individualized options for managing COPD based on specific patient characteristics.

MeiLan K Han, MD, MS, is professor of internal medicine and chief of the division of pulmonary and critical care medicine at the University of Michigan Health, in Ann Arbor, MI. Han's research focus is on defining phenotypes in COPD using imaging. She is a lead investigator for several NIH sponsored COPD studies and serves as a spokesperson for the American Lung Association and board member of the COPD Foundation. She is currently a deputy editor for the American Journal of Respiratory and Critical Care Medicine and serves as a member of the GOLD scientific committee, responsible for developing the internationally recognized consensus statement on COPD diagnosis and management.