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

Zelalem Temesgen, Colleen F. Kelley, Frank Cerasoli, Adrian Kilcoyne, Dale Chappell, Cameron Durrant, Omar Ahmed, Gabrielle Chappell, Victoria Catterson, Christopher Polk, Andrew Badley, Vincent C. Marconi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number218744
JournalThorax
DOIs
StateAccepted/In press - 2022

Keywords

  • ARDS
  • COVID-19
  • Critical Care
  • Cytokine Biology
  • GM-CSF
  • Pneumonia
  • Respiratory Infection

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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