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C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy: results from
Zelalem Temesgen1, Colleen F Kelley2, Frank Cerasoli3
1Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA temesgen.zelalem@mayo.edu.
Insights
Lenzilumab improved survival without ventilation in COVID-19 patients with low C-reactive protein (CRP) levels. Baseline CRP levels below 150 mg/L identified patients who benefited most from lenzilumab treatment.
Area of Science:
- Immunology
- Critical Care Medicine
- Pharmacology
Background:
- COVID-19 severity correlates with granulocyte macrophage colony-stimulating factor (GM-CSF) and C-reactive protein (CRP) levels.
- Lenzilumab, an anti-GM-CSF monoclonal antibody, showed promise in improving survival without ventilation (SWOV) in COVID-19 patients during the LIVE-AIR trial.
Purpose of the Study:
- To assess the utility of baseline C-reactive protein (CRP) levels in guiding lenzilumab treatment for hospitalized COVID-19 patients.
- To determine if baseline CRP can predict lenzilumab efficacy in improving SWOV.
Main Methods:
- A subanalysis of the randomized, blinded, controlled LIVE-AIR trial (N=520) was conducted.
- Hospitalized COVID-19 participants with hypoxemia received lenzilumab or placebo alongside standard treatments.
- The primary endpoint was SWOV through Day 28, analyzed by baseline CRP strata.
Main Results:
- Lenzilumab significantly improved SWOV in patients with baseline CRP <150 mg/L (90% vs. 79%; HR: 2.54; p=0.0009).
- No significant SWOV improvement was observed in patients with baseline CRP ≥150 mg/L (HR: 1.04; p=0.9058).
- A statistically significant interaction between CRP levels and lenzilumab efficacy was noted (p=0.044), with comparable safety profiles across CRP strata.
Conclusions:
- Hospitalized hypoxemic COVID-19 patients with baseline CRP <150 mg/L experienced the greatest clinical benefit from lenzilumab treatment.
- Baseline CRP is a valuable biomarker for stratifying patients likely to respond to lenzilumab therapy.
- Lenzilumab demonstrates a targeted efficacy in a specific subgroup of COVID-19 patients based on inflammatory markers.
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.
