What is the comparative efficacy and safety of dupilumab (Dupixent) vs ensifentrine in chronic obstructive pulmonary disease (COPD)?

Comparative Efficacy and Safety: Dupilumab vs Ensifentrine in COPD

Direct Comparison Not Available

There are no head-to-head trials or comparative data between dupilumab and ensifentrine in COPD, as these agents target fundamentally different patient populations and mechanisms of disease. The available evidence does not support comparing these medications directly, as they serve distinct therapeutic niches in COPD management.

Dupilumab: Evidence for Type 2 Inflammatory COPD

Patient Selection Criteria

Dupilumab is specifically indicated for patients with COPD who have:

• Blood eosinophil counts ≥300 cells/μL indicating type 2 inflammation 1, 2
• Moderate to severe airflow limitation (post-bronchodilator FEV1 30-70% predicted) 1
• High exacerbation risk (≥2 moderate or ≥1 severe exacerbation in prior year) despite triple therapy 1, 2
• Chronic productive cough for at least 3 months in the previous year 1

Efficacy Outcomes

Dupilumab added to triple therapy (ICS/LABA/LAMA) reduces moderate or severe exacerbations by 31% compared to placebo (annualized rate 0.794 vs 1.156; rate ratio 0.687,95% CI 0.595-0.793; p<0.0001) 1.

Additional benefits include:

• Lung function improvement: Prebronchodilator FEV1 increased by 83 ml more than placebo at week 12 (95% CI 42-125 ml; p<0.001), sustained through 52 weeks 2
• Quality of life: SGRQ score improved by 3.4 points more than placebo at week 52 (95% CI -5.5 to -1.3; p=0.002) 2
• Symptom reduction: E-RS-COPD score improved by 1.1 points more than placebo (95% CI -1.8 to -0.4; p=0.001) 2
• Severe exacerbations: Time to first severe exacerbation was significantly longer (hazard ratio 0.611,95% CI 0.409-0.912; p=0.016) 1

Efficacy Across Subgroups

Dupilumab demonstrates consistent benefit regardless of:

• BODE index scores (both ≤4 and >4 groups showed similar exacerbation reductions) 3
• Emphysema status (29-31% exacerbation reduction with or without emphysema; p for interaction=0.83) 4

Real-World Experience

In a prospective single-center study, dupilumab showed:

• 55% reduction in annualized exacerbation rate (3.47 to 1.55) 5
• Decreased severe exacerbations (median 1 to 0) 5
• Improved CAT scores (median 18 to 15) 5
• 61% patient satisfaction, with 74% willing to recommend to others 5

Safety Profile

Treatment-emergent adverse events, serious adverse events, discontinuations, and deaths were similar between dupilumab and placebo groups 1. In real-world use, only one patient (4%) reported skin-related side effects 5.

Ensifentrine: No Available Evidence

The provided evidence contains no data on ensifentrine for COPD. Current COPD guidelines do not mention ensifentrine as a recommended therapy 6, 7.

Standard COPD Management Context

Guideline-Recommended Therapies

For patients with moderate to severe COPD and exacerbations, established therapies include:

• LAMA/LABA dual therapy as initial maintenance (Evidence A) 6, 7
• Triple therapy (ICS/LAMA/LABA) for high exacerbation risk (Evidence A for lung function, Evidence B for exacerbations) 6
• LAMAs more effective than LABAs for exacerbation reduction (Evidence A) and hospitalizations (Evidence B) 6

ICS Safety Concerns

ICS use increases pneumonia risk (Evidence A), particularly in patients who:

• Currently smoke 6
• Are aged ≥55 years 6
• Have BMI <25 kg/m² 6
• Have severe airflow limitation or prior exacerbations/pneumonia 6

Clinical Decision Framework

For COPD patients with blood eosinophils ≥300 cells/μL and persistent exacerbations despite triple therapy, dupilumab represents a targeted add-on therapy with proven efficacy in reducing exacerbations and improving lung function 1, 2. This recommendation is based on two large phase 3 trials (BOREAS and NOTUS) enrolling 1,874 patients 1.

Without comparative data on ensifentrine, no evidence-based recommendation can be made regarding its use in COPD. Clinicians should rely on established guideline-recommended therapies (LAMA, LABA, ICS combinations) as the foundation of COPD management 6, 7.

Key Caveats

• Dupilumab requires specific biomarker-driven patient selection (eosinophils ≥300 cells/μL) and is only indicated as add-on to triple therapy 1, 2
• Cost and subcutaneous administration every 2 weeks were reported as treatment limitations by 48% and 21% of patients, respectively 5
• Dupilumab does not replace standard bronchodilator therapy—it is an add-on for a specific phenotype 1, 2