The edition · Pulmonology
Tezepelumab holds up outside the trial population, and an eosinophil count no longer has to be persistently raised to justify a biologic
A phase 4 study puts tezepelumab into the patients trials usually exclude, pooled mepolizumab data show intermittently raised eosinophils respond as well as persistently raised ones, and small-airway function at age seven predicts COPD at fifty-three.
The edition in brief
PASSAGE, a phase 4 single-arm study, gave tezepelumab to 286 US patients with severe uncontrolled asthma chosen to include the groups trials leave out - Black patients, adolescents, smokers with 10 or more pack-years, and people with coexisting mild-to-moderate COPD. The annualised exacerbation rate fell 70% (95% CI 63-75), from 2.88 to 0.87, with reductions of 54-77% across every phenotype and subgroup including blood eosinophils under 300. Pre-bronchodilator FEV1 rose 0.122 L overall and 0.212 L in those starting below 80% predicted. No new safety signals. Being single-arm and open-label, the before-and-after design cannot separate drug effect from regression to the mean. Pooled data from METREX, METREO and MATINEE show mepolizumab reduced COPD exacerbations in patients whose blood eosinophil count was intermittently raised (22-36% reduction) as well as persistently raised (12-27%), and in anyone with a count of 300 or more at any pre-randomisation time point (21%). Only patients persistently below 150 cells/microlitre gained nothing. The Tasmanian Longitudinal Health Study followed 2,314 people from age 7 to 53 and modelled trajectories of mid-to-small-airway function. Three impaired trajectories carried markedly raised odds of COPD by 53, with very wide confidence intervals. Associated factors included no breastfeeding, childhood asthma, wheeze, allergic rhinitis and pneumonia, maternal asthma and parental smoking before conception. The X-COPD trial of extracorporeal CO2 removal to enable early extubation in severe COPD exacerbations was stopped by its sponsor for financial reasons after 18 of a planned 192 patients; ventilation was shorter but nothing can be concluded about outcomes. The FDA acted on a supplemental application for the dexamethasone intravitreal implant Ozurdex, which has no respiratory implication.
Tezepelumab worked in the patients severe asthma trials usually leave out
Tezepelumab reduced exacerbations by 54-77% across every severe asthma phenotype tested, including low-eosinophil patients and smokers, so neither should be a reason to withhold a biologic referral.
A trial of extracorporeal CO2 removal in COPD stopped at 18 patients, for money
Extracorporeal CO2 removal shortened ventilation in a trial that stopped at 18 of a planned 192 patients, which is a reason to want the proper trial and not a reason to use the device.
Small-airway function at seven years old tracked with COPD at fifty-three
Impaired small-airway function trajectories beginning in early childhood were strongly associated with COPD by age 53, which puts childhood wheeze, pneumonia and smoke exposure into the COPD prevention conversation.
FDA acts on the dexamethasone intravitreal implant Ozurdex
The FDA acted on a supplement for the intravitreal dexamethasone implant Ozurdex; there is nothing in it for respiratory practice.
Take the eosinophil count before the prednisolone, not after
Judge a patient's eosinophil phenotype on counts taken when stable and at least four weeks clear of systemic steroids, and record the steroid status beside every value.
An eosinophil count that comes and goes still identifies a treatable COPD phenotype
In COPD, treat a blood eosinophil count of 300 or more at any point in the past year as evidence of a treatable type 2 phenotype - a persistently raised count is not required.
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