The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2025 report reflects a growing trend toward precision medicine, driven by a more refined understanding of COPD pathophysiology. The updated guidelines include two new FDA-approved medications, ensifentrine and dupilumab, in the follow-up therapy section to further reduce symptoms and disease exacerbations.
The GOLD report divides treatment into two phases: initial therapy and follow-up therapy. After starting a patient on a treatment, the focus shifts from initial guidelines to follow-up recommendations. A notable change in the 2025 update is the removal of inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) from the initial management phase. According to MeiLan Han, MD, MS, 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 acceptable, but there’s now guidance for moving forward.
Ensifentrine for Symptom Management
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. Phase 3 data has demonstrated 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.
Dupilumab for Type 2 Inflammation
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, it is now recognized 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.
Individualized Treatment Options
The 2025 GOLD update provides several options for patients who continue to experience COPD exacerbations. Azithromycin can be used as add-on therapy, particularly for non-smokers; roflumilast can be added if chronic bronchitis is the primary symptom; and dupilumab is a recommended option for patients with high eosinophil counts. Overall, the guidelines promote more targeted, individualized options for managing COPD based on specific patient characteristics.
