COPD-ST2OP trial: Astegolimab improves health status, not exacerbations in COPD

Astegolimab improved health status but did not significantly reduce exacerbation rates over 48 weeks of treatment compared with placebo in patients with moderate to very severe COPD, according to results from the COPD-ST2OP trial.

“Interleukin-33 signaling through interleukin-1 receptor-like 1 (ST2) has been shown to drive multiple types of inflammatory responses,” Ahmed J. Yousuf, PhD, from the department of respiratory science at the Institute for Lung Health of the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, U.K., and colleagues wrote in The Lancet Respiratory Medicine. “The effect of astegolimab, a selective ST2 monoclonal antibody, on frequency of COPD exacerbation, health-related quality of life, lung function, airway tissue inflammatory cells and safety and tolerability have not yet been assessed.”

COPD-ST2OP was a single-center, randomized, double-blind, placebo-controlled phase 2a trial that evaluated 81 participants with moderate to very severe COPD from October 2018 to August 2020. All participants were randomly assigned to subcutaneous astegolimab 490 mg (Genentech; n = 42; mean age, 67.6 years; 40% women) or subcutaneous placebo (n = 39; mean age, 70.8 years; 33% women) every 4 weeks for 44 weeks.

The primary outcome was COPD exacerbation rate during the 48 weeks assessed in the intention-to-treat population with a prespecified subgroup analysis based on baseline blood eosinophil count. Secondary outcomes were focused on St. George’s Respiratory Questionnaire for COPD, FEV₁ and blood and sputum cell counts.

At 48 weeks, the COPD exacerbation rate was not significantly different between those assigned astegolimab or placebo (incidence rate ratio = 0.78; 95% CI, 0.53-1.14; P = .19) in the intention-to-treat analysis. When the researchers stratified participants by blood eosinophil count, there were 0.69 COPD exacerbations among those with 170 cells/µL or less compared with 0.83 COPD exacerbations among those with more than 170 cells/µL.

The mean difference in St. George’s Respiratory Questionnaire for COPD was –3.3 (P= .039) and the mean difference in FEV₁ was 40 mL (P= .094) between the treatment groups.

The difference in geometric mean ratios for blood eosinophil counts was 0.59 (95% CI, 0.51-0.69; P < .001) and the difference in sputum eosinophil counts was 0.25 (95% CI, 0.19-0.33; P < .001) between the two treatment groups.

The incidence of treatment-emergent adverse events was similar between those assigned astegolimab and those assigned placebo.

“Our findings support the need for more adequately powered trials of anti-ST2 for exacerbations of COPD,” the researchers wrote.