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Division of Pulmonary, Allergy and Critical Care Medicine

SarcoidosisTeamSurya Bhatt, M.D.

Surya Bhatt, M.D., an associate professor in the UAB Division of Pulmonary, Allergy, and Critical Care Medicine, reported in the New England Journal of Medicine that patients with COPD and type 2 inflammation who received the biologic agent dupilumab had fewer exacerbations, better lung function, and less severe respiratory symptoms than those who received a placebo. This is the first time a biologic product, rather than a conventional drug, has been shown to be effective in treating COPD.

Regardless of severity, COPD flares lead to a poorer quality of life, increased hospitalizations, and an increased risk of death. Type 2 inflammation is associated with a higher risk of COPD exacerbations and may be indicated by elevated blood eosinophil counts. Between 20% and 40% of patients with COPD have evidence of type 2 inflammation. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for two key drivers of type 2 inflammation, interleukin-4, and interleukin-13.

Type 2 inflammation is associated with several pathologic processes in COPD, including airway hyperreactivity and fibrosis, airway remodeling, mucociliary dysfunction, and mucus hypersecretion. In the study, Bhatt looked at patients with a blood eosinophil count of at least 300 cells per microliter who were at an elevated exacerbation risk despite standard triple inhaler therapy. He assigned them to two groups to receive either subcutaneous dupilumab or placebo once every two weeks. The study's primary endpoint was the annualized rate of moderate or severe flares.

Dupilumab was associated with a 30% reduction in the rate of COPD flares over the 52-week course of the study. The biologic was also associated with meaningful improvements in lung function and health-related quality of life, as well as fewer severe respiratory symptoms compared to placebo. These improvements were observed within 2 to 4 weeks after the initiation of dupilumab and were sustained throughout the 52-week trial period.

The clinical improvements associated with dupilumab observed in this trial confirm the role of interleukin-4 or interleukin-13 (or both) in the pathologic pathways of this COPD subpopulation with type 2 inflammation—a role that extends beyond the role of interleukin-5 and eosinophils. The reduction in the frequency of exacerbations and the improvement in lung function with dupilumab were more pronounced among patients who had a fractional exhaled nitric oxide (FeNO) level of 20 ppb or higher at baseline.

"Dupilumab has the potential to impact the vicious cycle of exacerbations and lung function decline in patients who have COPD with type 2 inflammation and high exacerbation risk, who are already on optimal inhaled triple therapy," said Surya Bhatt, M.D. "Dupilumab significantly improves respiratory symptoms and also helped improve health-related quality of life measures."