The BOREAS and NOTUS trials established that dupilumab reduces exacerbations in COPD with type 2 inflammation. This pooled analysis asks what that meant in terms a patient and a health system recognise: admissions and steroid burden.
Both trials were phase 3, randomised, double-blind and placebo-controlled, enrolling patients aged 40 to 85 with COPD, moderate-to-severe airflow limitation, and a screening blood eosinophil count of 300 cells per microlitre or above. A total of 938 received dupilumab 300 mg and 936 placebo for 52 weeks.
Emergency department visits or hospital admissions of any duration fell by 38% (rate ratio 0.62, 95% CI 0.43 to 0.90, p=0.0121), and the risk of a first such event fell by 45% (hazard ratio 0.55, 95% CI 0.38 to 0.78, p=0.0010). Systemic corticosteroid use fell by 42% in patients experiencing severe exacerbations (rate ratio 0.58, 95% CI 0.38 to 0.89) and by 28% in those with moderate exacerbations (rate ratio 0.72, 95% CI 0.60 to 0.87).
The corticosteroid finding deserves more attention than it usually gets. Cumulative oral steroid exposure in COPD is a slow driver of osteoporosis, diabetes, cataract and adrenal suppression, and a 42% reduction in a frequently exacerbating patient is several grams of prednisolone over a few years. That is a distinct benefit from exacerbation reduction, and it is easier to explain to a patient than a rate ratio.
The eligibility constraint remains the eosinophil count of 300 or above, which is a minority of COPD patients. Measuring it, more than once and when stable, is the prerequisite step and it is done inconsistently.
- Measure blood eosinophils in COPD when the patient is stable and off steroids, and repeat before deciding on eligibility
- Where eosinophils are 300 cells per microlitre or above and exacerbations continue on triple therapy, dupilumab reduces admissions by 38%
- Count the steroid saving as a separate benefit — 42% less systemic corticosteroid in patients with severe exacerbations
- Record cumulative oral steroid exposure in the notes; it is the number that drives long-term harm
- This does not apply below the 300 cells per microlitre threshold used in both trials
The statistics, in plain English
The confidence intervals here are wide because admissions are relatively uncommon events: 0.43 to 0.90 for the rate ratio means the true reduction could be anywhere from 10% to 57%. That imprecision does not undermine the direction, which is consistent across three separate outcomes, but it does mean the headline 38% should be quoted as approximate. Note also that this is a post hoc pooled analysis of outcomes that were not the trials' primary endpoints — the exacerbation reduction was already established, and these analyses describe its consequences rather than testing a new hypothesis.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for pulmonology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free