In patients with chronic obstructive pulmonary disease characterized by eosinophilia and a failure to respond to triple therapy, does adding dupilumab improve outcomes?
For a very high-risk group of patients with COPD with eosinophilia, adding dupilumab to standard triple therapy results in 1 fewer moderate exacerbation about every 3 years. Although the primary outcome was moderate to severe exacerbations, 90% of those exacerbations were of moderate severity (requiring antibiotic or systemic glucocorticoid) and did not require an emergency visit or hospitalization. At a cost of $37,000 per year, this does not seem to be even remotely cost-effective.
Plan de l'etude:
Randomized controlled trial (double-blinded)
Dupilumab is a monoclonal antibody that reduces inflammation by blocking interleukin-4 and interleukin-13. These investigators identified 939 adults, aged between 40 and 80 years, with a history of tobacco use, a forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio of less than 0.70, postbronchodilator FEV1 of 30% to 70% of predicted, and an absolute eosinophil count of at least 300 per microliter. All patients had been taking standard triple therapy with a glucocorticoid, long-acting beta agonist, and a long-acting muscarinic agonist. All participants also must have had at least 2 moderate exacerbations or one severe exacerbation in the past year. Those with combined chronic obstructive pulmonary disease (COPD) and asthma were excluded. At baseline, the mean age of the participants was 65 years, 66% were men, 85% were White, 30% were current smokers, and the average number of pack-years was 40. The study took place at 275 sites in 24 countries. Groups were balanced at baseline and analysis was by intention to treat. Patients were randomized to receive dupilumab 300 mg every 2 weeks for 1 year or matching placebo. The primary outcome was the number of moderate or severe exacerbations per year. A moderate exacerbation was one that resulted in treatment with an antibiotic, a systemic corticosteroid, or both. A severe exacerbation was one that led to an emergency care visit, hospitalization, or death. There were 0.78 moderate to severe exacerbations per year in the dupilumab group and 1.10 in the placebo group (absolute difference 0.32/year; rate ratio 0.70; 95% CI 0.58 - 0.86). Put another way, the typical participant taking dupilumab will have 1 fewer exacerbation every 3 years. There was no difference between groups in serious adverse events (13.6% vs 15.5% for placebo) or deaths (1.5% vs 1.7% for placebo). The authors do not specify how many exacerbations were moderate and how many were severe in the main article but acknowledge in an appendix that the rate of severe exacerbations was not significantly different: 0.072 per year for dupilumab and 0.086 for placebo (relative risk 0.85; 95% CI 0.45 - 1.60).
Mark H. Ebell, MD, MS
University of Georgia