NOTUS
Trial question
What is the role of dupilumab in patients with COPD with type 2 inflammation?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
32.0% female
68.0% male
N = 935
935 patients (303 female, 632 male).
Inclusion criteria: patients with COPD who had a blood eosinophil count ≥ 300 cells/mL.
Key exclusion criteria: diagnosis or a history of asthma; COPD diagnosis for < 12 months prior to randomization; significant pulmonary disease other than COPD; cor pulmonale.
Interventions
N=470 dupilumab (subcutaneous dose of 300 mg every 2 weeks).
N=465 placebo (matching placebo every 2 weeks).
Primary outcome
Incidence of annualized rate of moderate or severe exacerbations
0.86
1.3
1.3 events...
1.0 events...
0.7 events...
0.3 events...
0.0 events...
Dupilumab
Placebo
Significant
decrease ▼
Significant decrease in the incidence of annualized rate of moderate or severe exacerbations (0.86 events/year vs. 1.3 events/year; RR 0.66, 95% CI 0.54 to 0.82).
Secondary outcomes
Significantly greater improvement in least-square mean prebronchodilator FEV1 at week 12 (0.139 L vs. 0.057 L; MD 0.082, 95% CI 0.04 to 0.12).
Significantly greater improvement in least-square mean prebronchodilator FEV1 at week 52 (0.115 L vs. 0.054 L; MD 0.062, 95% CI 0.01 to 0.11).
Significantly greater reduction in least-square mean St. George's Respiratory Questionnaire total score at week 52 (9.8 points vs. 6.4 points; MD 3.4, 95% CI 0.9 to 5.8).
Safety outcomes
No significant difference in adverse and serious adverse events.
Conclusion
In patients with COPD who had a blood eosinophil count ≥ 300 cells/mL, dupilumab was superior to placebo with respect to the incidence of annualized rate of moderate or severe exacerbations.
Reference
Surya P Bhatt, Klaus F Rabe, Nicola A Hanania et al. Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation. N Engl J Med. 2024 Jun 27;390(24):2274-2283.
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