Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial
| Autor: | Dorothy Cheung, Weily Soong, Steven G. Kelsen, Xiaoying Yang, Rajita Pappu, David F. Choy, Elliot Israel, Geoffrey Chupp, Christopher E. Brightling, Tracy Staton, Alice Fong, Michael J. Dolton, Ajit Dash, Ioana Agache, Wiebke Theess |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Immunology Population Placebo Antibodies Monoclonal Humanized law.invention 03 medical and health sciences Leukocyte Count 0302 clinical medicine Randomized controlled trial Double-Blind Method law Internal medicine medicine Clinical endpoint Immunology and Allergy Humans Single-Blind Method Anti-Asthmatic Agents Respiratory system education Adverse effect Asthma education.field_of_study business.industry Middle Aged medicine.disease Interleukin-33 Interleukin-1 Receptor-Like 1 Protein Interleukin 33 Eosinophils 030104 developmental biology Treatment Outcome 030228 respiratory system Disease Progression Female business |
| Zdroj: | The Journal of allergy and clinical immunology. 148(3) |
| ISSN: | 1097-6825 |
| Popis: | Background The 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 mAb, 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. Objectives This study evaluated astegolimab efficacy and safety in patients with severe asthma. Methods This double-blind, placebo-controlled, dose-ranging study (ZENYATTA [A Study to Assess the Efficacy and Safety of MSTT1041A in Participants With Uncontrolled Severe Asthma]) randomized 502 adults with severe asthma to subcutaneous placebo or 70-mg, 210-mg, or 490-mg doses of astegolimab every 4 weeks. The primary endpoint was the annualized asthma exacerbation rate (AER) at week 54. Enrollment caps ensured ∼30 patients who were eosinophil-high (≥300 cells/μL) and ∼95 patients who were eosinophil-low ( Results Overall, adjusted AER reductions relative to placebo were 43% (P = .005), 22% (P = .18), and 37% (P = .01) for 490-mg, 210-mg, and 70-mg doses of astegolimab, respectively. Adjusted AER reductions for patients who were eosinophil-low were comparable to reductions in the overall population: 54% (P = .002), 14% (P = .48), and 35% (P = .05) for 490-mg, 210-mg, and 70-mg doses of astegolimab. Adverse events were similar in astegolimab- and placebo-treated groups. Conclusions Astegolimab reduced AER in a broad population of patients, including those who were eosinophil-low, with inadequately controlled, severe asthma. Astegolimab was safe and well tolerated. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect