What are the implications of the BOREAS (Boreas trial) trial on patient treatment?

BOREAS Trial: Clinical Implications for COPD Treatment

Dupilumab 300 mg subcutaneously every 2 weeks should be added to standard triple therapy in patients with COPD who have blood eosinophil counts ≥300 cells/μL and elevated exacerbation risk despite maximal inhaled therapy, as it reduces moderate or severe exacerbations by 30% and improves lung function. 1, 2

Patient Selection Criteria

The BOREAS trial established specific eligibility requirements that define the target population for dupilumab therapy 2:

• Age and smoking history: Current or former smokers aged 40-85 years with ≥10 pack-years 1
• COPD severity: Post-bronchodilator FEV1/FVC ratio <0.7 and FEV1 30-70% predicted 1
• Type 2 inflammation marker: Blood eosinophil count ≥300 cells/μL during screening 2
• Exacerbation history: ≥2 moderate or ≥1 severe exacerbation in the previous year while on triple therapy 1
• Symptomatic disease: Chronic productive cough for ≥3 months in the previous year 1
• Key exclusions: History of asthma, other pulmonary diseases, or systemic diseases associated with elevated eosinophils 1

Primary Efficacy Outcomes

Exacerbation Reduction

Dupilumab demonstrated robust efficacy in reducing COPD exacerbations 2:

• Annualized moderate/severe exacerbation rate: 0.78 with dupilumab vs 1.10 with placebo (rate ratio 0.70; 95% CI 0.58-0.86; P<0.001) 2
• Absolute risk reduction: 30% reduction in exacerbation rate 1
• Time to first severe exacerbation: Significantly prolonged with dupilumab (hazard ratio 0.611; 95% CI 0.409-0.912; P=0.016) 1

Important caveat: While the annualized rate of severe exacerbations alone showed a trend favoring dupilumab (0.084 vs 0.124), this did not reach statistical significance (rate ratio 0.674; 95% CI 0.438-1.037; P=0.073) 1. The primary benefit is in preventing moderate exacerbations and delaying time to severe exacerbations.

Lung Function Improvement

Dupilumab produced sustained improvements in lung function 2:

• Week 12 prebronchodilator FEV1: Increased by 160 ml with dupilumab vs 77 ml with placebo (difference 83 ml; 95% CI 42-125; P<0.001) 2
• Durability: This improvement was sustained through week 52 2

Quality of Life and Symptom Benefits

Patient-reported outcomes showed meaningful improvements 2:

• SGRQ score at week 52: Improved by -9.7 with dupilumab vs -6.4 with placebo (difference -3.4; 95% CI -5.5 to -1.3; P=0.002) 2
• E-RS-COPD score at week 52: Improved by -2.7 with dupilumab vs -1.6 with placebo (difference -1.1; 95% CI -1.8 to -0.4; P=0.001) 2

Efficacy Across Patient Subgroups

Emphysema Status

A critical finding from BOREAS is that dupilumab efficacy is independent of emphysema presence 3:

• Patients with emphysema: 29% reduction in exacerbations (RR 0.71; 95% CI 0.53-0.95) 3
• Patients without emphysema: 31% reduction in exacerbations (RR 0.69; 95% CI 0.53-0.89) 3
• No treatment interaction: P=0.8296 for exacerbations, P=0.6438 for FEV1 improvement 3

This means dupilumab should be considered regardless of emphysema status in patients meeting other eligibility criteria 3.

Safety Profile

The pooled analysis of BOREAS and NOTUS trials demonstrated acceptable safety 1:

• Treatment-emergent adverse events: Similar between dupilumab and placebo groups 1
• Serious adverse events: Balanced between groups 1
• Discontinuation rates: Similar rates of adverse events leading to treatment discontinuation 1
• Mortality: Adverse events leading to death were balanced between groups 1

Clinical Implementation Algorithm

Step 1: Identify patients with COPD on triple therapy (ICS + LABA + LAMA) who continue to have exacerbations 1

Step 2: Verify exacerbation history: ≥2 moderate or ≥1 severe exacerbation in past year 1

Step 3: Measure blood eosinophil count during stable state (≥300 cells/μL required) 2

Step 4: Confirm chronic productive cough (≥3 months in past year) and symptomatic disease 1

Step 5: Exclude asthma history and other pulmonary/systemic diseases causing eosinophilia 1

Step 6: Initiate dupilumab 300 mg subcutaneously every 2 weeks as add-on to continued triple therapy 2

Step 7: Assess response at 12 weeks (expect FEV1 improvement and symptom reduction) 2

Mechanism and Rationale

Dupilumab blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation in COPD 2. This represents a targeted approach for patients with a specific inflammatory endotype characterized by elevated eosinophils, addressing underlying disease pathophysiology rather than just symptom control 1.

Common Pitfalls to Avoid

Do not use dupilumab in patients with asthma history, as these patients were explicitly excluded from BOREAS 1. The distinction between COPD with type 2 inflammation and asthma-COPD overlap is critical.

Do not rely on a single eosinophil measurement—screening values should be obtained during stable disease, not during exacerbations when eosinophils may be artificially suppressed 2.

Do not discontinue triple therapy when initiating dupilumab—it is an add-on treatment, not a replacement 2.

Do not expect immediate severe exacerbation prevention—while time to first severe exacerbation is prolonged, the primary benefit is in reducing moderate exacerbations and improving lung function 1, 2.

Positioning in Treatment Paradigm

Dupilumab represents the first biologic therapy demonstrating efficacy in COPD with type 2 inflammation, offering a personalized treatment approach for patients who remain symptomatic and at high exacerbation risk despite maximal inhaled therapy 1. The consistent efficacy across 1,874 patients in the pooled BOREAS and NOTUS analysis, with benefits observed regardless of emphysema status, supports its role as a standard add-on therapy for appropriately selected patients 1, 3.