Dupilumab helps patients with COPD, type 2 inflammation avoid negative outcomes

Key takeaways:

• This analysis used BOREAS and NOTUS trial data.
• Clinically important outcomes in this patient population were related to hospitalization, exacerbations, lung function and symptoms.

SAN FRANCISCO — The likelihood for avoidance of five clinically important outcomes in patients with COPD and type 2 inflammation was greater with dupilumab vs. placebo, according to findings from a win ratio analysis.

These data on dupilumab (Dupixent; Sanofi, Regeneron) were presented at the American Thoracic Society International Conference.

“Dupilumab is already approved for eligible patients with uncontrolled COPD, but these data provide further granularity on the potential impact,” Sanjay Ramakrishnan, PhD, MBBS, FRACP, senior lecturer at The University of Western Australia and research group leader at the Institute for Respiratory Health, told Healio. “When compared to placebo, patients on dupilumab had a decreased likelihood of a composite of events including death, hospitalization, worsening symptoms and lung function decline.

“Physicians can now clearly explain to patients the ways in which they stand to benefit with adding dupilumab into their COPD management plan: running the COPD race with dupilumab means you are 31% more likely to avoid a combination of potentially debilitating outcomes,” Ramakrishnan said.

In this win ratio analysis, Ramakrishnan and colleagues assessed adults with moderate to severe COPD and type 2 inflammation (blood eosinophil count ≥ 300 cells/μL) receiving triple therapy from the BOREAS and NOTUS phase 3 trials to find out the difference in clinically important endpoints at 52 weeks between patients receiving 300 mg dupilumab every 2 weeks (n = 938) and patients receiving placebo (n = 936).

Notably, a win ratio analysis is “a simple way to appreciate the benefit of [a] treatment” using the most clinically important outcomes, Ramakrishnan told Healio.

“Assessing multiple endpoints simultaneously in clinical trials can be challenging because not all outcomes have equivalent clinical importance,” Ramakrishnan said. “A win ratio analysis provides a way to evaluate key outcomes in tandem, but also ranks them in order of clinical importance, allowing for a more complete and appropriate comparison of multiple endpoints between dupilumab and placebo.”

The most clinically important outcome in this patient population was “avoiding hospital,” according to the analysis. Researchers also identified moderate exacerbations, lung function loss and symptom deterioration as clinically important outcomes. All four factors plus death made up one outcome.

“The approach creates a single measurement that provides a more accurate reflection of treatment efficacy that takes into account the impact of different clinical outcomes on a patient’s life,” Ramakrishnan told Healio.

All incorporated into one outcome, researchers reported that the likelihood for avoidance of death, hospitalization, exacerbations, worsening symptoms and worsening lung function was 31% greater (win ratio, 1.31; 95% CI, 1.15-1.48) in the dupilumab vs. placebo group.

“Patients receiving dupilumab are 31% more likely than placebo to ‘win’ on a combination of important outcomes,” Ramakrishnan said.

Dupilumab continued to be favored over placebo when broken down into the individual clinically important outcomes, according to the analysis.

Researchers highlighted that dupilumab had more wins — achievement of the more desirable outcome — vs. losses than placebo for death or a hospital admission/ED visit lasting 24 hours or longer (7.6% vs. 5.6%), moderate exacerbation or ED visit lasting less than 24 hours (22.1% vs. 17.9%) and total number of moderate or severe exacerbations during the evaluated 52 weeks (3.8% vs. 2.8%).

“What was quite striking was every 16th patient treated with dupilumab stopped having exacerbations completely,” Ramakrishnan said. “This is incredible, considering participants were having an average of two exacerbations in the previous year.”

Dupilumab also had more wins vs. losses for percent-predicted post-bronchodilator FEV₁ worsening of at least 100 mL at week 52 compared with placebo (12.1% vs. 8.2%), according to the analysis. Lastly, improvement in St. George’s Respiratory Questionnaire or Respiratory Symptom Tool for COPD scores was won more than lost by dupilumab vs. placebo (2% vs. 1.5%).

“We are pleased that the results were in line with what we would have expected based on the pivotal phase 3 trials for dupilumab in COPD, underscoring how it improves multiple, clinically important signs and symptoms of disease compared to placebo,” Ramakrishnan told Healio.

Looking ahead, Ramakrishnan said this analysis may have an impact on future trials in patients with COPD.

“These data could inform novel ways of conducting clinical trials in COPD to researchers and funders, by demonstrating a robust unified approach to simultaneously rank and assess outcomes of clinical importance to patients,” Ramakrishnan told Healio.

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For more information:

Sanjay Ramakrishnan, PhD, MBBS, FRACP, can be reached at pulmonology@healio.com.