Researchers at the American Thoracic Society International Conference in San Francisco presented compelling new data demonstrating that dupilumab significantly improves outcomes for patients with COPD and type 2 inflammation. The analysis revealed that patients receiving dupilumab were 31% more likely than those on placebo to avoid a combination of negative outcomes including death, hospitalization, exacerbations, worsening symptoms, and lung function decline.
Dr. Sanjay Ramakrishnan, senior lecturer at The University of Western Australia and research group leader at the Institute for Respiratory Health, who presented the findings, explained: "Dupilumab is already approved for eligible patients with uncontrolled COPD, but these data provide further granularity on the potential impact. Physicians can now clearly explain to patients the ways in which they stand to benefit with adding dupilumab into their COPD management plan."
Win Ratio Analysis Provides Comprehensive Assessment
The researchers conducted a win ratio analysis using data from the BOREAS and NOTUS phase 3 trials, which included 938 patients receiving 300 mg dupilumab every 2 weeks and 936 patients receiving placebo. All participants had moderate to severe COPD with type 2 inflammation (blood eosinophil count ≥ 300 cells/μL) and were receiving triple therapy.
The win ratio methodology allowed researchers to evaluate multiple endpoints simultaneously while ranking them in order of clinical importance. "Assessing multiple endpoints simultaneously in clinical trials can be challenging because not all outcomes have equivalent clinical importance," Dr. Ramakrishnan noted. "A win ratio analysis provides a way to evaluate key outcomes in tandem, but also ranks them in order of clinical importance."
The analysis identified avoiding hospitalization as the most clinically important outcome for COPD patients, followed by moderate exacerbations, lung function loss, and symptom deterioration.
Dupilumab Demonstrates Superiority Across All Outcomes
When examining individual outcomes, dupilumab consistently outperformed placebo:
- Death or hospital admission/ED visit lasting 24 hours or longer: 7.6% wins vs. 5.6% losses
- Moderate exacerbation or ED visit lasting less than 24 hours: 22.1% wins vs. 17.9% losses
- Total number of moderate or severe exacerbations during 52 weeks: 3.8% wins vs. 2.8% losses
- Percent-predicted post-bronchodilator FEV1 worsening of at least 100 mL at week 52: 12.1% wins vs. 8.2% losses
- Improvement in St. George's Respiratory Questionnaire or Respiratory Symptom Tool for COPD scores: 2% wins vs. 1.5% losses
"What was quite striking was every 16th patient treated with dupilumab stopped having exacerbations completely," Dr. Ramakrishnan emphasized. "This is incredible, considering participants were having an average of two exacerbations in the previous year."
Clinical Implications for COPD Management
Dupilumab (Dupixent), developed by Sanofi and Regeneron, is a monoclonal antibody that targets the IL-4 and IL-13 pathways involved in type 2 inflammation. The drug has already received regulatory approval for eligible patients with uncontrolled COPD, but these new findings provide additional evidence of its clinical benefits.
The results are particularly significant given the substantial burden of COPD, which affects millions worldwide and is characterized by progressive airflow limitation and recurrent exacerbations that can lead to hospitalization and increased mortality risk.
For clinicians treating patients with COPD and type 2 inflammation, these findings offer valuable guidance on the potential benefits of incorporating dupilumab into treatment regimens. The comprehensive analysis suggests that dupilumab can help patients avoid a range of negative outcomes that significantly impact quality of life and disease progression.
Future Implications for Research
Dr. Ramakrishnan suggested that this analytical approach could influence future clinical trials in 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," he said.
The win ratio methodology used in this analysis may provide a more patient-centered framework for evaluating treatments, focusing on outcomes that matter most to those living with the disease rather than isolated clinical measurements.
As researchers continue to explore targeted therapies for COPD subtypes, this comprehensive approach to assessing treatment benefits could become increasingly important in determining which interventions provide the most meaningful improvements for patients.
