番茄社区

WASHINGTON -- Among chronic obstructive pulmonary disease (COPD) patients with type 2 inflammation at high risk for exacerbations despite being on standard triple therapy, adding dupilumab (Dupixent) was associated with clinically significant improvements, the phase III trial showed.

Over 52 weeks of treatment, addition of the biologic reduced the annualized rate of moderate or severe exacerbations by 30% compared with placebo, at 0.78 versus 1.10, respectively (rate ratio 0.70, 95% CI 0.58-0.86, P<0.001), meeting the study's primary endpoint, reported Surya Bhatt, MD, MSPH, of the University of Alabama at Birmingham.

Greater improvement in lung function, symptoms, and health-related quality of life were also seen with dupilumab, according to findings presented at the annual meeting of the American Thoracic Society (ATS) and published simultaneously in the .

Trials of several other biologics are underway in patients with COPD, but the dupilumab study is the first to show significant improvements in lung function, exacerbations, and other key patient outcomes, Bhatt told 番茄社区.

Biologic therapies have been used in asthma patients for 2 decades, but none have been approved for the treatment of COPD, and previously reported studies of the drugs have proven disappointing. Bhatt told 番茄社区 that new insights into the pathophysiology and pathobiology of COPD is driving the new research.

"We understand the molecular markers and the pathways involved in COPD better, and we are also better at identifying the specific endotypes in COPD that are more likely to respond to biologics," Bhatt said. "We now recognize that approximately 20% of COPD patients have type 2 inflammation, and targeting this seems to be making a difference in terms of reducing exacerbation frequency and improving lung function in these patients."

Patients in the dupilumab arm experienced significantly greater improvements in pre-bronchodilator forced expiratory volume in 1 second (FEV₁) at 12 weeks (160 vs 77 mL with placebo, P<0.001), and this difference was sustained through the end of the trial.

Health-related quality of life on the St. George's Respiratory Questionnaire (SGRQ) also improved with the biologic, with reductions of 9.7 points versus 6.4 with placebo (P=0.002).

And the dupilumab group had a 2.7-point reduction in respiratory symptoms from baseline at 52 weeks on the Evaluating Respiratory Symptoms in COPD (E-RS-COPD) scale, as compared with a 1.6-point reduction for the placebo group (P=0.001).

Pulmonologist Donald Mahler, MD, of Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, was not involved with the study but attended the ATS meeting session in which the findings were presented.

He told 番茄社区 that while dupilumab will benefit only the subset of patients with type 2 inflammation, the drug and other biologics targeting different pathways are poised to usher in a new era of targeted treatments for COPD.

The double-blind randomized BOREAS trial included COPD patients without asthma with blood eosinophil counts of at least 300/µL at high risk for exacerbations despite the use of standard triple therapy. Patients randomized to dupilumab received subcutaneous infusions of the biologic every 2 weeks at a dosage of 300 mg.

The annualized rate of exacerbations judged to be either moderate or severe was chosen as the main study endpoint. Key secondary endpoints included change in pre-bronchodilator FEV₁, changes in disease-related quality of life assessed by SGRQ, and symptom changes measured by E-RS-COPD scores.

Overall, 939 patients were randomized in the trial, 468 in the dupilumab group and 471 in the placebo group. A total of 95.1% and 93.4%, respectively, in the dupilumab and placebo groups completed the study. The mean age in both groups was 65 years, 84% were white, about two-thirds were male, and 30% were current smokers.

Adverse events were balanced in the two groups, including for the proportion of patients with events that led to discontinuation (3.0% in the dupilumab group and 3.4% in the placebo group), serious adverse events (13.6% vs 15.5%), and adverse events that led to death (1.5% and 1.7%), the researchers said.

The clinical improvements shown in the BOREAS trial "confirm the role of interleukin-4 or interleukin-13 (or both) in the pathophysiological characteristics of this COPD subpopulation with type 2 inflammation that extends beyond the role of interleukin-5 and eosinophils," Bhatt and colleagues noted.

"Dupilumab may play a role in reducing goblet-cell hyperplasia, mucus hypersecretion, and airway remodeling through its inhibition of the interleukin-4 or interleukin-13 pathway," they added.

The study was conducted during the COVID-19 pandemic, which may have affected both patient recruitment and the frequency of COPD exacerbations, Bhatt and colleagues acknowledged. The researchers also cited the small number of Black participants and lack of randomization by smoking status as study limitations.