Dupilumab may reduce COPD exacerbations in patients regardless of emphysema status: Study

A new study published in the journal of Respiratory Medicine showed that patients with type 2 inflammation and chronic obstructive pulmonary disease (COPD), with or without investigator-reported emphysema, showed comparable levels of dupilumab effectiveness. Significantly diminished lung function and a higher chance of exacerbations which are defined by increasing cough or dyspnea, an increase in the volume or purulence of sputum, or a combination of these symptoms that is frequently linked to chronic obstructive pulmonary disease. Despite the use of inhaled drugs, exacerbations are also linked to a higher risk of mortality from any cause, a faster deterioration in lung function, and an increased risk of recurrent exacerbations.

Although COPD has long been thought to include an enhanced innate immune response, there is emerging evidence that some people with the condition have type 2 inflammation. The interleukin-4 and interleukin-13 pathways raise fractional exhaled nitric oxide (FeNO) levels and, more generally, enhance eosinophil and type 2 inflammatory cell infiltrations in the lung. In the phase 3 BOREAS study, patients with type 2 inflammation and chronic obstructive pulmonary disease experienced fewer exacerbations and better lung function when treated with dupilumab, a completely human monoclonal antibody that targets the common receptor component for interleukin-4 and interleukin-13. Thus, this study was carried out by Surya Bhatt and colleagues to evaluate clinical outcomes in BOREAS patients according to their emphysema status.

Every two weeks for 52 weeks, patients with COPD with type 2 inflammation (screening blood eosinophils ≥300 cells/μL) receiving maximum inhaled treatment were randomized to receive either a placebo or an additional 300 mg of dupilumab. This study evaluated the change in prebronchodilator forced expiratory volume in 1 second (FEV1) from baseline to Week 12 in patients with and without investigator-reported emphysema, as well as the annualized rates of moderate/severe COPD exacerbations during a 52-week period.

A total of 306 out of 939 patients (32.6%) had investigator-reported emphysema at baseline. In individuals with and without emphysema, dupilumab decreased exacerbation rates by 29% and 31%, respectively, when compared to a placebo. With patients with and without emphysema, the prebronchodilator FEV1 least squares mean difference from baseline to Week 12 with dupilumab vs. placebo was 0.07 L and 0.09 L, respectively. The annualized rate of exacerbations and the decrease in prebronchodilator FEV1 did not show any treatment by emphysema interaction impact. Overall, dupilumab efficacy was similar in individuals with type 2 inflammation and COPD, whether or not they had investigator-reported emphysema.

Reference:

Bhatt, S. P., Rabe, K. F., Hanania, N. A., Vogelmeier, C. F., Bafadhel, M., Christenson, S. A., Papi, A., Singh, D., Laws, E., Dakin, P., Maloney, J., Lu, X., Bauer, D., Bansal, A., Robinson, L. B., & Abdulai, R. M. (2024). Dupilumab reduces exacerbations and improves lung function in patients with chronic obstructive pulmonary disease and emphysema: Phase 3 randomized trial (BOREAS). In Respiratory Medicine (p. 107846). Elsevier BV. https://doi.org/10.1016/j.rmed.2024.107846