1. In this randomized controlled trial, dupilumab use was associated with significantly fewer chronic obstructive pulmonary disease (COPD) exacerbations among patients with type two inflammation as compared to a placebo.
2. The incidence of adverse events leading to treatment discontinuation or death and serious adverse events was not significantly different between groups.
Evidence Rating Level: 1 (Excellent)
Study Rundown: COPD is a lung disease which results in reduced pulmonary function. Patients with COPD exacerbations present with acute worsening of dyspnea and increased sputum volume and purulence. Type two inflammation is commonly found in patients with COPD, and key cytokines interleukin-4 and interleukin-13 are proposed to aid type two inflammatory cells to invade lung tissue. In this double-blind randomized trial, the interleukin-4 and interleukin-13 receptor blocker dupilumab was tested against a placebo in adult patients with COPD, blood eosinophil count of over 300 per microliter, and receiving background glucocorticoid-long acting muscarinic antagonist (LAMA)-long-acting beta-agonist (LABA) combination inhaler treatment. Patients were treated for 52 weeks, followed by a 12-week safety follow-up without treatment. The primary outcome of the rate of moderate or severe COPD exacerbations was significantly lower in the dupilumab group compared to the placebo group. For secondary outcomes, the prebronchodilator forced expiratory volume (FEV1) was significantly higher in the dupilumab group than in the placebo group for both weeks 12 and 52. For patient-reported outcomes, both the St. George’s Respiratory Questionnaire (SGRQ) and Evaluating Respiratory Symptoms in COPD (E-RS-COPD) scores significantly improved from baseline in the dupilumab group compared to the placebo group. For safety, there were no significant differences between groups in adverse events or serious adverse events. As a limitation, non-White ethnicities were underrepresented, which may reduce generalizability.
Click to read the study in NEJM
Relevant Reading: Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease
In-Depth [randomized controlled trial]: In this phase three randomized trial, adult patients (40 to 80 years old) with COPD, a blood eosinophil count of over 300 per microliter, and who were receiving glucocorticoid-LAMA-LABA inhaler treatment were randomized to receive biweekly add-on dupilumab 300 mg (n=468) or a placebo (n=471) for 52 weeks. The annualized rate of moderate-to-severe COPD exacerbations was significantly lower in the dupilumab group (0.78; 95% Confidence Interval [CI], 0.64 to 0.93) as compared to the placebo group (1.10; 95% CI, 0.93 to 1.30; rate ratio, 0.70; 95% CI, 0.58 to 0.86; p<0.001). For secondary outcomes focused on lung function, the improvement in prebronchodilator FEV1 from baseline was significantly higher in the dupilumab group at week 12 (least squares mean difference, 83 mL; 95% CI, 42 to 125; p<0.001) and at week 52 (least squares mean difference, 83 mL; 95% CI, 38 to 128; p<0.001). Similar differences in prebronchodilator FEV1 change from baseline were found in the subgroup of patients with a baseline fractional concentration of exhaled nitric oxide level of 20 parts per billion or higher. For quality-of-life outcomes, improvement in the SGRQ and E-RS-COPD scores from baseline were both significantly higher in the dupilumab group compared to placebo. For safety, overall (77.4% and 76.0% in dupilumab and placebo groups, respectively) and serious (13.6% and 15.5%, respectively) adverse events were similar between groups. In summary, the present study demonstrates that dupilumab treatment may reduce the rate of exacerbations and improve the quality of life in patients with COPD and type two inflammation.
Image: PD
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