Dupilumab is a human monoclonal antibody that blocks the receptor shared by interleukin-4 (IL-4) and IL-13, both of which are key to the development of type 2 inflammation in chronic obstructive pulmonary disease (COPD). A recent study published in The New England Journal of Medicine discusses the results of a second phase III trial on dupilumab in a subset of COPD patients.

Study: Dupilumab for COPD with blood eosinophil evidence of type 2 inflammation. Image Credit: Wildflower_macro / Shutterstock.com

Treating COPD

COPD is a progressive lung condition that is associated with high morbidity and mortality. Although it is a chronic condition, COPD is marked by exacerbations that may lead to more rapid clinical progression.

Current care for COPD patients often involves triple inhaler therapy that comprises a glucocorticoid, long-acting muscarinic antagonist (LAMA), and long-acting beta-agonist (LABA).

Despite the availability of this treatment, many COPD patients are still at a 50% risk of exacerbations. Therefore, there remains an urgent need for more effective COPD therapies to prevent these events, as well as achieve better lung function in these patients to ultimately improve their quality of life.

About the study

The NOTUS RCT was a multi-nation multicenter study sponsored by Regeneron and Sanofi. The current study was designed to evaluate the efficacy of dupilumab over a 52-week period in symptomatic COPD patients with increased eosinophil counts, which is indicative of chronic type 2 inflammation.

All patients were randomized to experimental or control groups. The experimental group received 300 mg of subcutaneous dupilumab, whereas the control group received a placebo, which was repeated every two weeks.

Both groups were assessed for the rate of moderate to severe exacerbations. The researchers also examined the change in forced expiratory volume in one second (FEV1) from baseline before the administration of bronchodilators at weeks 12 and 52.

FEV1 measures the amount of air blown out in one second with effort, with a low FEV1 indicating airflow obstruction. At week 52, the St. George’s Respiratory Questionnaire (SGRQ), with scores from 0 to 100, was also provided to study participants.

What did the study show?

The study included 935 patients, all of whom had eosinophil counts of 300 cells/mL or more. All study participants were between 40 and 86 years of age.

Less than 30% of the study cohort identified as current smokers. However, all study participants had a history of smoking ten or more packets each day.

All patients had been prescribed triple inhaler therapy for at least three months, with their current dose stable for one month or more at the time of the study. Moreover, all patients had a history of two or more moderate or one severe exacerbation over the past year and required glucocorticoid treatment for at least one moderate exacerbation. At least one exacerbation occurred while on triple inhaler therapy.

FEV1 to forced vital capacity (FVC) ratios were below 0.7, with FEV1 before bronchodilators between 30-70% of expected values. Of the 935 patients, 721 were eligible for the analysis of results at week 52.

Moderate or severe exacerbations occurred at a rate of 0.86 and 1.3 with dupilumab and placebo, respectively. Thus, the risk of moderate to severe exacerbations was reduced by about 33% in the experimental group.

FEV1 increased at week 12, with the difference in mean values between the two groups being 82 mL. At week 52, this difference was reduced to 62 mL.

SGRQ scores did not change significantly during the study period. Adverse events also occurred at similar rates in both groups, which was expected from previous reports on dupilumab.

Conclusions

The use of dupilumab in COPD patients with raised eosinophil counts was accompanied by a reduced risk of moderate to severe exacerbations. Lung function was also improved with dupilumab compared to the placebo. There were no differences in the effects observed with age, sex, current or former smoker status, baseline lung function, or the presence of emphysema.

The NOTUS trial confirms robust and consistent clinical efficacy of interleukin-4 and interleukin-13 blockade in patients with COPD with evidence of type 2 inflammation.”

The current study was conducted during the coronavirus disease 2019 (COVID-19) pandemic, which may have reduced the exposure of patients to respiratory viruses. Another limitation of the current study was that both cohorts primarily consisted of White patients, thus limiting the generalizability of the findings. Thus, future studies with a more diverse study population that is adequately powered for other outcomes are needed.