The edition · Pulmonology
Astegolimab cut COPD exacerbations by 15% regardless of eosinophil count
A pooled analysis of ALIENTO and ARNASA in 2,682 patients found an anti-ST2 antibody reduced moderate and severe exacerbations by 15% on a fortnightly schedule, and severe exacerbations by 32% — in a population enrolled irrespective of blood eosinophils. Dupilumab separately cut emergency visits by 38% in the eosinophilic phenotype.
The edition in brief
Biologics in COPD moved on two fronts today, and the difference between them is the population. Astegolimab, an anti-ST2 antibody, was tested in ALIENTO and ARNASA in 2,682 patients with COPD and frequent exacerbations, enrolled irrespective of blood eosinophil count and irrespective of chronic bronchitis. Fortnightly dosing reduced annualised moderate and severe exacerbations by 15% (rate ratio 0.85) and four-weekly by 12% (0.88). Severe exacerbations fell by 32% on the fortnightly schedule (0.68), a nominally significant secondary endpoint. It was well tolerated. That an unselected COPD population responded at all is the notable part — every biologic that has worked in COPD so far has needed an eosinophil threshold. Dupilumab, by contrast, was studied in BOREAS and NOTUS in patients selected for eosinophils of 300 cells per microlitre or more. In 1,874 patients it reduced emergency department visits and hospital admissions by 38%, delayed time to first event with a hazard ratio of 0.55, and cut systemic corticosteroid use by 42% after severe exacerbations and 28% after moderate ones. Also today: AZIMUNE, a 40-patient mechanistic trial, showed azithromycin increases rhinovirus-induced interferon-beta and lambda in bronchial epithelium and lowers IL-33 — a plausible mechanism for a clinical effect already established. And the ATS has issued a new clinical practice guideline on non-invasive respiratory support in acute respiratory failure.
An anti-ST2 antibody reduced COPD exacerbations without needing an eosinophil threshold
Astegolimab reduced moderate and severe COPD exacerbations by 15% and severe exacerbations by 32% in a population enrolled irrespective of blood eosinophil count.
Dupilumab cut emergency visits and steroid exposure in eosinophilic COPD
In COPD with eosinophils of 300 or more, dupilumab reduced emergency visits and admissions by 38% and cut systemic corticosteroid use by 28 to 42% depending on exacerbation severity.
Azithromycin restored epithelial interferon responses to rhinovirus in uncontrolled asthma
Azithromycin increased rhinovirus-induced epithelial interferon-beta and lambda and reduced IL-33 in uncontrolled asthma, offering a non-antibacterial mechanism for its established exacerbation benefit.
The ATS has published a guideline on non-invasive respiratory support in acute respiratory failure
The American Thoracic Society has published an official clinical practice guideline on non-invasive respiratory support in adults with acute respiratory failure.
In COPD biologics, read the enrolment criterion before the effect size
Before comparing effect sizes between two trials of a biologic, check whether they enrolled the same population — a smaller effect in an unselected group may matter more than a larger one in an enriched one.
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