More Good News About Dupixent for COPD Subgroup With Type 2 Inflammation | 2024 ATS

Dupixent (dupilumab) reduced moderate or severe exacerbations in people with chronic obstructive pulmonary disease (COPD) who have evidence of type 2 inflammation by 34%, according to results presented at the 2024 American Thoracic Society (ATS) International Conference in San Diego.

The results from this trial, called NOTUS, confirm positive findings from a previous phase 3 trial, called BOREAS, that were presented at the ATS meeting last year.

Between 20% and 40% of people with COPD have evidence of type 2 inflammation, and its presence is associated with an increased risk of exacerbations, episodes of severe worsening of COPD that are characterized by shortness of breath, fatigue and a change in the color of sputum from being clear to a deep yellow, green or brown.

Dupixent is a monoclonal antibody that blocks the interleukin-4 and interleukin-13 pathways that are instrumental in the cascade of events that constitute type 2 inflammation. The FDA has approved it as a treatment for five conditions in which wayward type 2 inflammation is a central contributing cause: atopic dermatitis, asthma with an eosinophilic phenotype, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis and prurigo nodularis.

In both trials, Dupixent was used as on add-on therapy to the trio of inhaled therapies commonly used to manage COPD: a glucocorticoid agent, a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA).

The results of the NOTUS trial were published simultaneously with the ATS presentation in The New England Journal of Medicine.

Surya P. Bhatt, M.D., M.S.P.H.

Lead author and corresponding author Surya P. Bhatt, M.D., M.S.P.H., a professor of medicine in the Division of Pulmonary, Allergy and Critical Care Medicine at the University of Alabama at Birmingham, and his colleagues enrolled 935 patients in the NOTUS trial at 329 sites in 29 countries. All the participants had blood eosinophil counts of 300 cells per microliter or higher, a threshold that was used as biomarker for the presence of type 2 inflammation (the average blood eosinophil count was 407 cells per microliter) Nearly all (98.8%) of participants were on the inhaled glucocorticoid-LAMA-LABA combination.

The researchers randomly assigned the participants to receive a subcutaneous injection of Dupixent every two weeks or a placebo injection for a year. The primary outcome was annualized rate of moderate or severe exacerbations. Moderate exacerbation was defined as an exacerbation that needed to be treated with antibiotics, a systemic glucocorticoid steroid or both. A severe one was defined as an exacerbation that led to a hospitalization or an emergency room visit

Bhatt and his colleagues analyzed the data generated by the trial after positive interim analysis, so the number of patients included in the analysis dropped from 935 to 721. On the primary end point of the annualized rate of moderate and severe exacerbations, they found a difference between the Dupixent group and the placebo group emerged early and grew larger. At 52 weeks, rate in the Dupixent group was 34% lower than in the placebo group (.86 vs. 1.30). They noted that the difference in exacerbations was similar in prespecified subgroups of patients that were defined by age, sex, smoking status, lung function at the time of enrollment in the study and history of exacerbations.

The difference favored the Dupixent group in forced expiratory volume in 1 second, a common test of lung function, emerged at 12 weeks and continued throughout the trial period. Other results on secondary end points favored Dupixent.

Bhatt and his colleagues wrote in the discussion section of The New England Journal of Medicine paper that their result “confirm the role of type 2 inflammation in the pathobiologic disease mechanisms in a subgroup of patients with COPD and the rule of dupilumab in treating this distinct COPD endotype.”