- Design
- Self-controlled case series within a prospective cohort, plus RCT meta-analysis
- Population
- 480 adults with severe asthma from 85 US sites
- Primary outcome
- Severe exacerbation rate on vs off biologic
- Effect
- IRR 0.43 (95% CI 0.39-0.48); RCT rate ratio 0.53 (0.47-0.60)
This analysis of CHRONICLE, a US prospective cohort of adults with severe asthma treated by specialists, compared exacerbation rates during periods on and off biologics in 480 patients from 85 sites, and set them against a meta-analysis of six randomised trials. Published in the European Respiratory Journal on 22 October 2026.
Biologics were associated with fewer severe exacerbations both in the trials (rate ratio 0.53) and in real-world use (incidence rate ratio 0.43). Benefit was larger in patients who would have met trial criteria for minimal smoking history, previous exacerbations, raised exhaled nitric oxide and raised blood eosinophils. Exclusions based on spirometry, COPD or bronchiectasis, which removed the most patients from trials, did not predict response.
This suggests some patients are being kept off biologics, or out of trials, for reasons that do not affect benefit.
The self-controlled design handles fixed differences between patients but not changes over time, such as better adherence once a biologic starts.
- Prioritise biologics for patients with frequent exacerbations and raised eosinophils or FeNO
- Do not exclude a patient from biologic consideration solely on FEV1 or coexisting bronchiectasis
- Expect a smaller benefit in people with a significant smoking history
- Recheck adherence and inhaler technique before starting a biologic
Why it matters
Trial exclusions based on lung function may be denying benefit to patients who would respond.
Don't overread it
The subgroup comparisons are observational and cannot be read as proof that excluded groups respond equally.
The statistics, in plain English
An incidence rate ratio of 0.43 means exacerbations occurred at less than half the rate on biologics. Ratios of ratios below 1 show where benefit was larger, for example about twice as large in non-smokers.
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