Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: a randomized clinical trial
Abstract
BACKGROUND
The interleukin (IL)-33/ST2 pathway is linked with asthma susceptibility. Inhaled allergens, pollutants, and respiratory viruses, which trigger asthma exacerbations, induce release of IL-33, an epithelial-derived "alarmin." Astegolimab, a human IgG2 monoclonal antibody, selectively inhibits the IL-33 receptor, ST2. Approved biologic therapies for severe asthma mainly benefit patients with elevated blood eosinophils (Type 2-high), but limited options are available for patients with low blood eosinophils (Type 2-low). Inhibiting IL-33 signaling may target pathogenic pathways in a wider spectrum of asthmatics.
OBJECTIVE
This study evaluated astegolimab efficacy and safety in patients with severe asthma.
METHODS
This double-blind, placebo-controlled, dose-ranging study (ZENYATTA) randomized 502 adults with severe asthma to subcutaneous placebo or 70-mg, 210-mg, or 490-mg astegolimab every 4 weeks. The primary endpoint was the annualized asthma exacerbation rate (AER) at Week 54. Enrollment caps ensured ∼30 eosinophil-high (≥300 cells/μL) and ∼95 eosinophil-low (<300 cells/μL) patients per arm.
RESULTS
Overall, adjusted AER reductions relative to placebo were 43% (p=0.005), 22% (p=0.18), and 37% (p=0.01) for 490-mg, 210-mg, and 70-mg astegolimab, respectively. Adjusted AER reductions for eosinophil-low patients were comparable to reductions in the overall population: 54% (p=0.002), 14% (p=0.48), and 35% (p=0.05) for 490-mg, 210-mg, and 70-mg astegolimab. Adverse events…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 502 participants or records.
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