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 Patients Based on the NOTUS Study

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

Patient Selection Criteria from NOTUS Study

The NOTUS study specifically evaluated dupilumab in COPD patients with the following key characteristics:

• Blood eosinophil count ≥300 cells/µL at screening 2
• History of exacerbations despite triple therapy (LAMA/LABA/ICS) 2
• Moderate to severe airflow limitation (post-bronchodilator FEV1/FVC <0.7 and FEV1 30-70% predicted) 2

Analysis of Each Patient Option:

1. 70-year-old female, current smoker, history of asthma, eosinophil count 500 cells/µL

   • Highest eosinophil count (500 cells/µL) among all options
   • History of asthma, which is associated with type 2 inflammation
   • Age within the study population range (mean age in NOTUS was 65.0 ± 8.3 years) 2

2. 50-year-old male, former smoker, history of heart failure, eosinophil count 350 cells/µL

   • Adequate eosinophil count but heart failure may complicate treatment
   • Younger than the mean age in the study population

3. 90-year-old male, current smoker, history of CAD, eosinophil count 400 cells/µL

   • Age significantly outside the study population (NOTUS included patients aged 40-85 years) 3
   • Cardiovascular comorbidity may increase risk

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

   • Eosinophil count below the required threshold of ≥300 cells/µL for the NOTUS study 2

Evidence Supporting This Selection

The FDA label for dupilumab indicates that in the NOTUS trial, patients had a mean screening blood eosinophil count of 538 (±333) cells/µL 2. The 70-year-old female with 500 cells/µL most closely matches this profile.

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.

Importance of Asthma History

While the NOTUS study excluded patients with a current diagnosis of asthma 3, the GOLD guidelines note that "asthma may be a risk for the development of chronic airflow limitation and COPD" 4. This suggests that patients with a history of asthma (not current asthma) may represent a phenotype with type 2 inflammation that could benefit from dupilumab.

Clinical Considerations

• Eosinophil Count: Higher eosinophil counts (≥300 cells/µL) predict better response to dupilumab in COPD 1
• Age: The mean age in the NOTUS study was 65.0 years 2, making the 70-year-old patient appropriate
• Smoking Status: Both current and former smokers were included in the NOTUS study (29.5% were current smokers) 2
• Comorbidities: History of asthma suggests type 2 inflammatory pathway involvement, which is the target of dupilumab

Potential Adverse Effects to Monitor

• Injection site reactions
• Nasopharyngitis
• Potential for ocular surface disorders (though these are more common in atopic dermatitis than in respiratory indications) 4, 5

Conclusion

Based on the NOTUS study criteria, the 70-year-old female with asthma history and eosinophil count of 500 cells/µL is the most appropriate candidate for dupilumab initiation, as she best matches the study population that demonstrated benefit and has the strongest markers of type 2 inflammation that would respond to IL-4/IL-13 pathway blockade.