Advances have been made in the development of biologic therapies targeting type 2 inflammatory pathways in chronic obstructive pulmonary disease (COPD), with monoclonal antibodies emerging as particularly promising agents. Several presentations at the recent American Thoracic Society International Conference 2026 (ATS 2026) shared data that build on this research.

Following these presentations, featured expert Nicola A. Hanania, MD, MS, was interviewed by Conference Reporter Medical Director Lauren Weinand, MD. Clinical perspectives from Dr Hanania on these findings are presented here.

At ATS 2026, I discussed the current role of type 2 biologics in COPD during a state-of-the-art educational session. We know that type 2 inflammation is important in COPD. It is driven by several mediators, including epithelial cytokines (eg, TSLP and IL-33), IL-13, IL-4, and IL-5. All these cytokines can propagate changes in the airway, including those relating to remodeling, mucus production, destruction in the terminal lung, and eosinophilic recruitment. Of course, these changes result in airflow limitation symptoms, lung function decline, and COPD exacerbation.

Approximately 20% to 40% of patients with COPD demonstrate type 2 inflammatory features, commonly identified by elevated blood eosinophil counts and/or fractional exhaled nitric oxide levels. This subtype of COPD inflammation has been associated with an increased risk of exacerbations, hospitalization, readmission, and lung function decline. It is also a predictor of corticosteroid responsiveness. Despite adequate treatment with triple therapy, 30% to 60% of patients with COPD continue to have exacerbations. This is why it is important to look at other interventions, including type 2 biologic agents.

Currently, we have 2 US Food and Drug Administration (FDA)–approved type 2 biologics for COPD: dupilumab and mepolizumab. Dupilumab blocks IL-4R, a common receptor for both IL-4 and IL-13. IL-4 is instrumental in macrophage polarization, eosinophilic recruitment, and IgE production. IL-13 is important in airway remodeling, lung parenchymal destruction, and mucus hypersecretion. Mepolizumab blocks IL-5, which recruits and activates eosinophils. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 report recommends add-on maintenance therapy with dupilumab or mepolizumab in patients who continue to experience exacerbations, have high blood eosinophil counts, and are already on triple therapy.

Both agents have been studied in large populations of patients with COPD at a high risk of exacerbation. Mepolizumab was the first biologic to be investigated in 2 large trials, METREX and METREO, which looked at patients with eosinophilic COPD. Due to conflicting results between these 2 studies, the MATINEE study was performed. Dupilumab was studied in 2 large trials, BOREAS and NOTUS. In all these mepolizumab and dupilumab trials, participants were required to be on triple therapy and must have experienced 2 or more exacerbations in the preceding year, with evidence of type 2 inflammation based on blood eosinophil counts of 300 cells/µL or higher. The primary end point of these studies was annualized moderate or severe COPD exacerbations.

The METREX and METREO trials of mepolizumab were initially done in patients with a blood eosinophil count cutoff of 150 cells/µL and a high risk of exacerbation. The METREX study demonstrated positive results, with an 18% exacerbation reduction. However, the METREO study did not meet the primary end point, so the 2-year MATINEE trial was conducted. This study enrolled patients with COPD on triple therapy who had blood eosinophil counts of 300 cells/µL or higher at screening and 150 cells/µL or higher within 12 months prior to screening. In MATINEE, there was a 21% reduction in moderate or severe exacerbations. The safety of mepolizumab was confirmed in this trial, but there was no effect on lung function or patient-reported outcomes.

The BOREAS and NOTUS studies of dupilumab reported a reduction in moderate or severe exacerbations of 30% and 34%, respectively. Baseline blood eosinophil counts and fractional exhaled nitric oxide levels were both predictive of exacerbation reduction. Statistically significant improvements in lung function were also reported. Importantly, there were improvements in patients’ symptoms based on the Evaluating Respiratory Symptoms in COPD (E-RS:COPD) questionnaire (PPD Evidera Patient-Centered Research) and quality of life based on the St. George’s Respiratory Questionnaire (SGRQ; City St. George’s, University of London). The safety profile of dupilumab was robust in these studies, with no signal of an increased risk of adverse events compared with placebo.

There are additional biologics in the pipeline that target the epithelial alarmins IL-33 and TSLP. Some have completed phase 3 trials, but none are currently approved by the FDA. Future studies will tell us more about how all these biologic therapies perform in the real-world setting, whether they affect other comorbidities that these patients have, and whether they work better in one subgroup of patients with COPD vs others. Additional important questions for future research include whether we should be using biologics earlier and whether treatment timing affects outcomes.

Where does that leave us with the type 2 biologics? There are many unmet needs that still need to be examined, including the potential impact on disease progression and whether they have disease-modifying effects. Do these biologic therapies affect disease stability and activity? Will they affect patient-reported outcomes in the long-term? What is their role in the acute setting? Several posters that my colleagues Surya P. Bhatt, MD, MSPH (poster P1493), Simon Couillard, MD, FRCPC, MSc (poster P1486), Dave Singh, MD (poster P1506), and I (poster P1429) presented at ATS 2026 offered insights into some of these remaining questions.