C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy : results from the randomised phase 3 'LIVE-AIR' trial
© 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..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
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| Enthalten in: |
Thorax - 78(2023), 6 vom: 27. Juni, Seite 606-616 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Temesgen, Zelalem [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.05.2023 Date Revised 22.12.2023 published: Print-Electronic ClinicalTrials.gov: NCT04351152 Citation Status MEDLINE |
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| doi: |
10.1136/thoraxjnl-2022-218744 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy |b results from the randomised phase 3 'LIVE-AIR' trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 18.05.2023 | ||
| 500 | |a Date Revised 22.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04351152 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 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. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a PARTICIPANTS: Hospitalised COVID-19 participants (N=520) with SpO2 ≤94% on room air or requiring supplemental oxygen but not invasive mechanical ventilation | ||
| 520 | |a INTERVENTIONS: Lenzilumab (1800 mg; three divided doses, q8h, within 24 hours) or placebo infusion alongside corticosteroid and remdesivir treatments | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: Hospitalised hypoxemic patients with COVID-19 with baseline CRP <150 mg/L derived the greatest clinical benefit from treatment with lenzilumab | ||
| 520 | |a TRIAL REGISTRATION NUMBER: NCT04351152; ClinicalTrials.gov | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a ARDS | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Critical Care | |
| 650 | 4 | |a Cytokine Biology | |
| 650 | 4 | |a GM-CSF | |
| 650 | 4 | |a Pneumonia | |
| 650 | 4 | |a Respiratory Infection | |
| 650 | 7 | |a C-Reactive Protein |2 NLM | |
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| 650 | 7 | |a lenzilumab |2 NLM | |
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| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
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| 700 | 0 | |a LIVE-AIR Study Group |e verfasserin |4 aut | |
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