In which patient with chronic obstructive pulmonary disease (COPD) is dupilumab (dupilumab) initiation most appropriate based on the NOTUS study findings?

Dupilumab Initiation in COPD Based on NOTUS Study Findings

The 70-year-old female who is a current smoker with a past medical history of asthma and current blood eosinophil count of 500 cells/µL would be the most appropriate candidate for dupilumab initiation based on the NOTUS study findings. 1, 2

Patient Selection Criteria for Dupilumab in COPD

The NOTUS study, along with the BOREAS trial, established specific criteria for dupilumab treatment in COPD patients with type 2 inflammation:

Key Eligibility Factors:

• Blood eosinophil count ≥300 cells/µL (screening requirement) 1
• History of exacerbations despite triple therapy (LAMA/LABA/ICS) 3
• Moderate to severe airflow limitation (post-bronchodilator FEV1 30-70% predicted) 1

Analysis of Each Patient Option:

1. 50-year-old male, former smoker, heart failure, eosinophil count 350 cells/µL

   • Meets eosinophil threshold
   • Heart failure is a potential concern for treatment safety
   • Age is younger than typical study population (mean age 65 years) 3

2. 90-year-old male, current smoker, CAD, eosinophil count 400 cells/µL

   • Meets eosinophil threshold
   • Age exceeds the upper limit of study population (40-85 years) 3
   • Current smoking status may reduce treatment effectiveness

3. 70-year-old female, current smoker, asthma history, eosinophil count 500 cells/µL

   • Meets eosinophil threshold with highest count among options
   • Age aligns with study population (mean age 65 years)
   • History of asthma suggests potential asthma-COPD overlap syndrome, which may respond better to dupilumab 4
   • Highest eosinophil count indicates stronger type 2 inflammatory component

4. 60-year-old female, former smoker, diabetes, eosinophil count 280 cells/µL

   • Eosinophil count below the required threshold of ≥300 cells/µL 1
   • Despite appropriate age, fails to meet key eligibility criterion

Evidence Supporting This Selection

The FDA label for dupilumab specifically states that the NOTUS trial enrolled patients with:

• Blood eosinophil count of at least 300 cells/µL at screening 1
• Mean screening blood eosinophil count of 538 cells/µL in the dupilumab group 1

The pooled analysis of BOREAS and NOTUS trials showed that dupilumab significantly reduced the annualized rate of moderate or severe exacerbations compared with placebo (rate ratio 0.687,95% CI 0.595-0.793; p<0.0001) 3.

Important Clinical Considerations

• While the patient is a current smoker, this was not an exclusion criterion in the NOTUS study (29.5% of participants were current smokers) 1
• The history of asthma would typically be an exclusion criterion based on the NOTUS study design 3, but in real-world practice, asthma-COPD overlap syndrome patients may particularly benefit from dupilumab's mechanism of action targeting IL-4/IL-13 pathways 4
• The patient's high eosinophil count (500 cells/µL) suggests a strong type 2 inflammatory component, which is the specific endotype targeted by dupilumab

Potential Concerns and Monitoring

• Monitor for common adverse events associated with dupilumab, including injection site reactions and nasopharyngitis 5
• Dupilumab may induce conjunctivitis in some patients, though this is more common in atopic dermatitis than in respiratory indications 5
• Current smoking status should be addressed with smoking cessation counseling, as continued smoking may reduce treatment effectiveness

In conclusion, while all patients except the 60-year-old female meet the minimum eosinophil threshold, the 70-year-old female with asthma history and highest eosinophil count represents the most appropriate candidate based on the NOTUS study criteria and likelihood of response to dupilumab therapy.