Astegolimab reduced COPD exacerbations regardless of eosinophil count

Design

Prespecified pooled analysis of two randomised, double-blind, placebo-controlled trials

Population

2682 people with COPD, frequent exacerbations and smoking history

Primary outcome

Annualised rate of moderate or severe exacerbations

Effect

2-weekly RR 0.85 (95% CI 0.76–0.96); 4-weekly RR 0.88 (0.78–0.99); severe exacerbations 2-weekly RR 0.68 (0.52–0.87)

ALIENTO and ARNASA randomised patients with COPD, frequent exacerbations and a smoking history to astegolimab, an anti-ST2 antibody targeting the IL-33 pathway, every 2 or 4 weeks, or placebo for 52 weeks on top of maintenance treatment. Patients were enrolled regardless of blood eosinophil count or chronic bronchitis. This prespecified pooled analysis included 2682 participants.

Moderate or severe exacerbations fell by 15% with 2-weekly dosing and 12% with 4-weekly dosing. Severe exacerbations fell by 32% with 2-weekly dosing, a nominally significant secondary result. The drug was well tolerated.

The relevance is the population. Current biologics for COPD, dupilumab and mepolizumab, need an eosinophilic phenotype, which leaves many frequent exacerbators without an option. Astegolimab may fill that gap, but the benefit is modest, regulatory status is not established from this record and cost will limit use in India.

• Optimise inhaled triple therapy, vaccination and rehabilitation first
• Check blood eosinophils to identify patients eligible for existing biologics
• Note astegolimab as a possible future option for frequent exacerbators without eosinophilia
• Weigh a 15% reduction against the cost of a biologic

Why it matters

It points to a biologic option for frequent COPD exacerbators who lack type 2 inflammation.

Don't overread it

The effect is modest, and the severe exacerbation result is nominal rather than formally tested.

The statistics, in plain English

A rate ratio of 0.85 (95% CI 0.76–0.96) is a 15% reduction; for someone with three exacerbations a year, that is about half an exacerbation fewer. The 32% cut in severe exacerbations is labelled nominally significant because it sits outside the formal testing hierarchy, so it is supportive rather than confirmed.

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