Table of Contents
Background
Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory airway
disease. The epithelial-derived IL-33 and its receptor ST2 have been implicated in
airway inflammation and infection. We aimed to determine whether astegolimab, a selective
ST2 IgG2 monoclonal antibody, reduces exacerbations in COPD.
Methods
2a trial in moderate-to-very severe COPD. Participants were randomly assigned (1:1)
with a web-based system to received 490 mg subcutaneous astegolimab or subcutaneous
placebo, every 4 weeks for 44 weeks. The primary endpoint was exacerbation rate assessed
for 48 weeks assessed with a negative binomial count model in the intention-to-treat
population, with prespecified subgroup analysis by baseline blood eosinophil count.
The model was the number of exacerbations over the 48-week treatment period, with
treatment group as a covariate. Safety was assessed in the whole study population
until week 60. Secondary endpoints included Saint George's Respiratory Questionnaire
for COPD (SGRQ-C), FEV1, and blood and sputum cell counts. The trial was registered with ClinicalTrials.gov, NCT03615040.
Findings
The exacerbation rate at 48 weeks in the intention-to-treat analysis was not significantly
different between the astegolimab group (2·18 [95% CI 1·59 to 2·78]) and the placebo
group (2·81 [2·05 to 3·58]; rate ratio 0·78 [95% CI 0·53 to 1·14]; p=0·19]). In the
prespecified analysis stratifying patients by blood eosinophil count, patients with
170 or fewer cells per μL had 0·69 exacerbations (0·39 to 1·21), whereas those with
more than 170 cells per μL had 0·83 exacerbations (0·49 to 1·40). For the secondary
outcomes, the mean difference between the SGRQ-C in the astegolimab group versus placebo
group was –3·3 (95% CI –6·4 to –0·2; p=0·039), and mean difference in FEV1 between the two groups was 40 mL (–10 to 90; p=0·094). The difference in geometric
mean ratios between the two groups for blood eosinophil counts was 0·59 (95% CI 0·51
to 0·69; p<0·001) and 0·25 (0·19 to 0·33; p<0·001) for sputum eosinophil counts. Incidence
of treatment-emergent adverse events was similar between groups.
Interpretation
In patients with moderate-to-very severe COPD, astegolimab did not significantly reduce
exacerbation rate, but did improve health status compared with placebo.
Funding
Funded by Genentech and National Institute for Health Research Biomedical Research
Centres.
