New pooled analysis data from the BOREAS and NOTUS phase 3 trials reveals that dupilumab maintains consistent therapeutic benefits in adults with COPD and type 2 inflammation, regardless of whether patients have cardiovascular or metabolic comorbidities. The findings, presented at the European Respiratory Society International Congress, provide reassuring evidence for clinicians treating COPD patients with complex medical histories.
Consistent Exacerbation Reduction Across Patient Subgroups
In a post hoc analysis of 1,874 adults with COPD and type 2 inflammation (blood eosinophil count ≥300 cells/μL), researchers evaluated whether cardiovascular or metabolic disease history affected dupilumab's efficacy. Patients received either 300 mg subcutaneous dupilumab (n=938) or placebo (n=936) every 2 weeks for 52 weeks while on triple therapy with long-acting beta agonists, long-acting muscarinic antagonists, and inhaled corticosteroids.
The analysis included 1,253 patients with cardiovascular disease history—defined as hypertension, heart failure, myocardial infarction, ischemic heart disease, atrial fibrillation, or other documented cardiac conditions—and 621 patients without such history. For metabolic disease, defined as diabetes, dyslipidemia, or obesity (BMI ≥30 kg/m²), 758 patients met the criteria while 1,116 did not.
"Dupilumab is already approved for eligible patients with COPD, and these findings emphasize that the presence of cardiovascular and metabolic comorbidities does not impact the important effect of dupilumab to alleviate two key aspects of disease: exacerbation reduction and lung function improvement," said John R. Hurst, MBBS, professor of respiratory medicine at University College London.
Both patient groups with and without cardiovascular disease history showed similar significant reductions in annualized moderate or severe exacerbations with dupilumab versus placebo—31% reduction in those with cardiovascular disease and 33% reduction in those without. Similarly, patients with metabolic disease experienced a 32% reduction while those without metabolic disease had a 31% reduction.
Significant Impact on Severe Exacerbations
A separate post hoc analysis focused specifically on severe exacerbations revealed even more compelling results. Dupilumab treatment resulted in significantly fewer patients experiencing at least one severe exacerbation compared to placebo (4.4% vs 6.4%). The drug demonstrated a 39% reduction in risk for at least one severe exacerbation at week 52 (HR=0.61; 95% CI, 0.41-0.91; P=.016).
"Severe exacerbations are associated with substantial short-term and long-term consequences, including significant loss of lung function and, in many cases, death," explained Surya P. Bhatt, MD, professor in the division of pulmonary, allergy and critical care medicine at The University of Alabama at Birmingham. "Preventing these events can significantly impact the life course of disease in these patients."
The time-to-first severe exacerbation and/or emergency department visit showed a significant 45% decreased risk among dupilumab recipients (adjusted HR=0.55; 95% CI, 0.38-0.78; P=.001). The adjusted annualized rate of severe exacerbations and/or emergency department visits was 38% lower in the dupilumab group compared to placebo (0.1 vs 0.16; P=.0121).
Lung Function and Corticosteroid Use Benefits
Lung function improvements remained consistent across subgroups. Patients with cardiovascular disease history showed a least-squares mean difference of +55 mL in prebronchodilator FEV1 with dupilumab versus placebo, while those without cardiovascular disease had a +104 mL improvement. For metabolic disease subgroups, improvements were +62 mL and +77 mL respectively for those with and without metabolic disease history.
Among patients who experienced at least one severe exacerbation, dupilumab treatment significantly reduced the duration of systemic corticosteroid use from 34 days in the placebo group to 20 days—a 42% reduction (P=.0126).
"The reduction in cumulative steroid use is clinically meaningful, in that we can potentially decrease the side effects associated with steroid use," Bhatt noted.
Safety Profile Remains Consistent
The safety analysis revealed no concerning differences between subgroups. Treatment-emergent adverse events occurred in similar proportions between dupilumab and placebo recipients in both cardiovascular disease groups (74% vs 72% with history; 69% vs 68% without history). Treatment-emergent serious adverse events also showed comparable rates (15% vs 18% with cardiovascular history; 11% vs 10% without cardiovascular history).
"It's important to note that the safety profile of dupilumab was not different in those with and without cardiovascular and metabolic comorbidities," Hurst emphasized.
Clinical Implications
These findings hold particular significance given that COPD patients with cardiovascular and metabolic comorbidities face higher risks of poor outcomes. The FDA approved dupilumab for treating adults with poorly controlled COPD with type 2 inflammation approximately one year ago.
"I would characterize the results as important and reassuring," Hurst said. "People with COPD and cardiovascular or metabolic comorbidities are at higher risk of poor outcomes, so to see that dupilumab has similar efficacy in these groups too is important in clinical practice."
The researchers indicated that future studies will continue to assess various subgroups of interest from the pivotal BOREAS and NOTUS clinical trials, potentially providing additional insights into dupilumab's therapeutic profile across diverse COPD patient populations.
