C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy: results from the randomised phase 3 'LIVE-AIR' trial.

Autor:	Temesgen Z; Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA temesgen.zelalem@mayo.edu., Kelley CF; Division of Infectious Diseases, Emory University School of Medicine, Grady Memorial Hospital, Atlanta, Georgia, USA., Cerasoli F; Medical Affairs, Rx Medical Dynamics, LLC, New York, New York, USA., Kilcoyne A; Humanigen Inc, Burlingame, California, USA., Chappell D; Humanigen Inc, Burlingame, California, USA., Durrant C; Humanigen Inc, Burlingame, California, USA., Ahmed O; Humanigen Inc, Burlingame, California, USA., Chappell G; Humanigen Inc, Burlingame, California, USA., Catterson V; BioSymetrics, Inc, New York, New York, USA., Polk C; Infectious Disease, Atrium Health, Charlotte, North Carolina, USA., Badley A; Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA., Marconi VC; Division of Infectious Disease, Emory University School of Medicine, Rollins School of Public Health, and Emory Vaccine Center, Atlanta, Georgia, USA.
Jazyk:	angličtina
Zdroj:	Thorax [Thorax] 2023 Jun; Vol. 78 (6), pp. 606-616. Date of Electronic Publication: 2022 Jul 06.
DOI:	10.1136/thoraxjnl-2022-218744
Abstrakt:	Objective: COVID-19 severity is correlated with granulocyte macrophage colony-stimulating factor (GM-CSF) and C reactive protein (CRP) levels. In the phase three LIVE-AIR trial, lenzilumab an anti-GM-CSF monoclonal antibody, improved the likelihood of survival without ventilation (SWOV) in COVID-19, with the greatest effect in participants having baseline CRP below a median of 79 mg/L. Herein, the utility of baseline CRP to guide lenzilumab treatment was assessed. Design: A subanalysis of the randomised, blinded, controlled, LIVE-AIR trial in which lenzilumab or placebo was administered on day 0 and participants were followed through Day 28. Participants: Hospitalised COVID-19 participants (N=520) with SpO2 ≤94% on room air or requiring supplemental oxygen but not invasive mechanical ventilation. Interventions: Lenzilumab (1800 mg; three divided doses, q8h, within 24 hours) or placebo infusion alongside corticosteroid and remdesivir treatments. Main Outcome Measures: The primary endpoint was the time-to-event analysis difference in SWOV through day 28 between lenzilumab and placebo treatments, stratified by baseline CRP. Results: SWOV was achieved in 152 (90%; 95% CI 85 to 94) lenzilumab and 144 (79%; 72 to 84) placebo-treated participants with baseline CRP <150 mg/L (HR: 2.54; 95% CI 1.46 to 4.41; p=0.0009) but not with CRP ≥150 mg/L (HR: 1.04; 95% CI 0.51 to 2.14; p=0.9058). A statistically significant interaction between CRP and lenzilumab treatment was observed (p=0.044). Grade ≥3 adverse events with lenzilumab were comparable to placebo in both CRP strata. No treatment-emergent serious adverse events were attributed to lenzilumab. Conclusion: Hospitalised hypoxemic patients with COVID-19 with baseline CRP <150 mg/L derived the greatest clinical benefit from treatment with lenzilumab. Trial Registration Number: NCT04351152; ClinicalTrials.gov. Competing Interests: Competing interests: ZT has received research support from Humanigen, Inc, unrestricted education support from Gilead, ViiV, and Merck (all to the institution); CP is a paid consultant to Gilead; CFK has received research support grants (to the institution) from NIH, CDC, Gilead Sciences and ViiV; VCM has received investigator-initiated research grants (to the institution) and consultation fees (both unrelated to the current work) from Eli Lilly, Bayer, Gilead Sciences and ViiV; CD, DC, OA, AK and GC are employees of, or consultants to, Humanigen, Inc.; VMC and FC are third-party agency consultants to Humanigen. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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