Tezepelumab in real-world severe asthma: exacerbations fell 70% across phenotypes

Design

Phase 4, single-arm, open-label real-world study (PASSAGE)

Population

286 US patients aged ≥12 with severe uncontrolled asthma, including under-represented groups

Primary outcome

Annualised asthma exacerbation rate, 12 months before vs after

Effect

2.88 to 0.87, 70% reduction (95% CI 63–75%)

PASSAGE was a phase 4, single-arm, open-label US study of tezepelumab in 286 people aged 12 and over with severe uncontrolled asthma, deliberately including groups under-represented in trials: low-eosinophil and non-allergic phenotypes, Black patients, adolescents, those with coexisting COPD and heavy smokers.

Annualised exacerbations fell from 2.88 in the year before to 0.87 in the year after starting tezepelumab (70% reduction, 95% CI 63–75%), and by 54–77% across subgroups. Pre-bronchodilator FEV1 rose by 122 mL overall. No new safety signals appeared.

Without a control group, some of the reduction reflects regression to the mean — patients start biologics at their worst. Still, the consistency across low-eosinophil and smoking subgroups supports tezepelumab's role where other biologics that target eosinophils are less suited.

• Consider tezepelumab for severe uncontrolled asthma with low eosinophils or non-allergic disease.
• Confirm adherence and inhaler technique before escalating to a biologic.
• Reassess exacerbations and control at 12 months to decide on continuation.
• Check cost and availability locally before discussion with patients.

Why it matters

It extends evidence to patients most trials excluded, including smokers and those with overlapping COPD.

Don't overread it

Single-arm before-and-after data — regression to the mean inflates the apparent effect.

The statistics, in plain English

Comparing the year before and after starting a drug tends to overstate benefit, because patients usually start treatment after an unusually bad year.

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