Tezepelumab worked across phenotypes in a real-world severe asthma population

Design

phase 4, multicentre, single-arm, open-label, 12-month study

Population

286 US patients aged ≥12 with severe uncontrolled asthma across eosinophil phenotypes and underrepresented groups

Primary outcome

annualised asthma exacerbation rate in the 12 months before versus after starting tezepelumab

Effect

2.88 to 0.87, a 70% reduction (95% CI 63–75%); FEV1 +0.122 L (0.07–0.17) at week 52

Severe asthma trials routinely exclude the patients who fill a severe asthma clinic: smokers, people with overlapping COPD, adolescents, and those with low blood eosinophils. PASSAGE was a phase 4, single-arm, open-label 12-month study designed around them, enrolling 286 US patients aged 12 and over with severe uncontrolled asthma, including eosinophil counts both above and below 300 cells/µL, with and without allergy, Black or African American patients, adolescents, those with comorbid mild-to-moderate COPD, and those with at least 10 pack-years.

The annualised exacerbation rate fell 70% (95% CI 63 to 75), from 2.88 in the year before tezepelumab to 0.87 in the year after, and by 54% to 77% across each phenotype and underrepresented group. Pre-bronchodilator FEV1 rose by a least-squares mean 0.122 L (0.07 to 0.17) at week 52 overall, and by 0.212 L (0.15 to 0.28) in those starting below 80% predicted. Between 51% and 91% of participants reached clinically meaningful improvement on the Asthma Control Questionnaire-6, the Asthma Impairment and Risk Questionnaire and the St George's Respiratory Questionnaire. No new safety signals emerged.

The design limits what this proves. A single-arm before-and-after comparison in patients selected for frequent exacerbations will show improvement from regression to the mean alone, and open-label symptom scores are not blinded to anything. What survives that is the consistency across groups — a drug that works only in the eosinophil-high patients should not have produced a 54% floor across phenotypes — and the FEV1 change, which is harder to talk a patient into.

• Consider tezepelumab in severe asthma with low blood eosinophils, where other biologics have less to offer
• Do not exclude patients with a smoking history or overlapping COPD from the biologic conversation
• Record exacerbation count for the 12 months before starting, so the comparison is real
• Repeat spirometry at a year rather than relying on symptom scores alone

Why it matters

The patients excluded from the registration trials are the ones sitting in the severe asthma clinic.

Don't overread it

Single-arm and open-label, comparing patients with their own previous year — this is not evidence of effect size against placebo.

The statistics, in plain English

A 70% fall in exacerbations sounds decisive but is measured against the patient's own previous year, with no control group — patients are enrolled after a bad year and tend to have a better one regardless. The confidence interval of 63 to 75% describes precision, not freedom from that bias. The FEV1 gain of 0.122 L is modest and around the threshold of what patients notice; the 0.212 L in those with impaired baseline function is more substantial. Open-label questionnaire outcomes in a single-arm study should be read as supportive, not primary.

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