Dupilumab Improves Outcomes for COPD, Type 2 Inflammation in Randomized Trial

Surya Bhatt, MD, MSPH

In a groundbreaking phase 3 clinical trial, investigators discovered patients with chronic obstructive pulmonary disease (COPD) who exhibited type 2 inflammation, experienced significant benefits when treated with dupilumab.¹

According to the data featured at the American Thoracic Society (ATS) 2023 International Conference in Washington, DC, a reduction in exacerbations, improved lung function, enhanced quality of life, and less severe respiratory symptoms were observed in these patients when compared with the placebo group.

COPD is associated with frequent exacerbations, and the study noted the risk of experiencing exacerbations is higher among patients with elevated blood eosinophil counts, or type 2 inflammation. Dupilumab, a fully human monoclonal antibody, has shown potential as a therapeutic intervention by targeting interleukin-4 and interleukin-13, key drivers of type 2 inflammation.

Randomized Trial Evaluates Dupilumab as COPD Therapy

The investigators, led by Surya Bhatt, MD, MSPH, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, conducted the double-blind, randomized trial aiming to evaluate the efficacy of dupilumab in patients with COPD presenting with elevated exacerbation risk and blood eosinophil counts of at least 300 per microliter, despite receiving standard triple therapy.

The trial involved subcutaneous administration of either dupilumab (300 mg) or placebo every 2 weeks. The primary endpoint was the annualized rate of moderate or severe COPD exacerbations.

Secondary endpoints included changes in prebronchodilator forced expiratory volume in 1 second (FEV1), scores on the St. George's Respiratory Questionnaire (SGRQ), and Evaluating Respiratory Symptoms in COPD (E-RS–COPD).

Dupilumab Effectively Demonstrates COPD Benefits

A total of 939 patients were randomized, with 468 assigned to the dupilumab group and 471 to the placebo group. Results showed the annualized rate of moderate or severe exacerbations was significantly lower in the dupilumab group (0.78; 95% confidence interval [CI], 0.64-0.93) compared with the placebo group (1.10; 95% CI, 0.93-1.30), which yielded a rate ratio of 0.70 (95% CI, 0.58-0.86; P < 0.001).

According to the data, from baseline to week 12 the prebronchodilator FEV1 significantly increased in the dupilumab group by a least-squares (LS) mean of 160 ml (95% CI, 126-195), while an increase of 77 ml was observed in the placebo group (95% CI, 42-112) (LS mean difference, 83 ml; 95% CI, 42 to 125; P < 0.001).

The investigators reported these differences in FEV1 were sustained through week 52, at which the dupilumab group exhibited an improved SGRQ score with an LS mean of -9.7 (95% CI, -11.3 to -8.1). Those in the placebo group demonstrated an improvement of -6.4 (95% CI, -8.0 to -4.8) (LS mean difference, -3.4; 95% CI, -5.5 to -1.3; P = 0.002).

Similarly, the E-RS–COPD score at week 52 revealed greater improvement in the dupilumab group, with an LS mean of -2.7 (95% CI, -3.2 to -2.2), compared with -1.6 (95% CI, -2.1 to -1.1) in the placebo group (LS mean difference, -1.1; 95% CI, -1.8 to -0.4; P = 0.001).

The study stated the incidence of adverse events leading to discontinuation, serious adverse events, and deaths were similar between the dupilumab and placebo groups.

In addition to observing lower annualized rate of exacerbations in patients treated with dupilumab, investigators acknowledged further findings.

“Dupilumab was also associated with significantly greater improvements in lung function and health-related quality of life and significantly less severe respiratory symptoms than those seen with placebo, and these differences were observed within 2 to 4 weeks after the initiation of dupilumab or placebo and were sustained throughout the 52-week trial period,” they wrote.

References:

1. Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts. N Engl J Med. 2023.