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Lookup NU author(s): Professor Anthony De SoyzaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The authors 2023.Background Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95). Methods ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ⩾2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay. Results Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70–1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27–1.12; p=0.26), while the OR was 0.31 (80% CI 0.09–1.06) in patents with high baseline serum IL-33/sST2 complex levels. Conclusions Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.
Author(s): Wilkinson T, De Soyza A, Carroll M, Chalmers JD, Crooks MG, Griffiths G, Shankar-Hari M, Ho L-P, Horsley A, Kell C, Lara B, Mishra B, Moate R, Page C, Pandya H, Raw J, Reid F, Saralaya D, Scott IC, Siddiqui S, Ustianowski A, van Zuydam N, Woodcock A, Singh D, ACCORD Collaborative Group
Publication type: Article
Publication status: Published
Journal: ERJ Open Research
Year: 2023
Volume: 9
Issue: 5
Print publication date: 01/09/2023
Online publication date: 02/10/2023
Acceptance date: 25/07/2023
Date deposited: 21/11/2023
ISSN (electronic): 2312-0541
Publisher: European Respiratory Society
URL: https://doi.org/10.1183/23120541.00249-2023
DOI: 10.1183/23120541.00249-2023
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