Impact of Fostamatinib on Inflammatory Biomarkers in Hospitalized Patients With COVID-19.
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Da Cruz Raquel S, Teague Heather L, Ramos-Benitez Marcos J, Malavez-Cajigas Sonya J, Williams Trenton, Miao Rui, Tian Xin, Lin Gefei, Busse Laurence W, Khan Akram, Moskowitz Ari, Hager David N, Rice Todd W, Ginde Adit A, Iovine Nicole M, Chen Peter, Safdar Basmah, Gibbs Kevin W, Javaheri Ali, de Wit Marjolein, Harkins Michelle, Hudock Kris, Merck Lisa H, Barksdale Aaron, Sturek Jeffrey M, Schrager Harry, Shapiro Nathan I, Lanspa Michael, Harris Estelle, Sellers Subhashini, Goodwin Andrew J, Tidswell Mark A, Filbin Michael R, Shotwell Matthew S, Semler Matthew W, Self Wesley H, Collins Sean P, Strich Jeffrey R, Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-4) Host Tissue Investigators
Аннотация
DESIGN: Secondary analyses of biomarkers from a randomized clinical trial.
SETTING: Multicenter randomized clinical trial.
PATIENTS: A total of 400 adults hospitalized with COVID-19 were enrolled in a phase 3 randomized clinical trial. Absolute neutrophil counts (ANCs) were analyzed across 392 patients and biomarkers were measured in 190 patients with available plasma samples.
INTERVENTIONS: Adults hospitalized with COVID-19 were randomized to receive either fostamatinib (150 mg bid) or placebo. ANCs and 24 biomarkers were assessed at day 0 and over time using a multiplexed Meso Scale Discovery assay (Meso Scale Diagnostics LLC, Rockville, MD).
MEASUREMENTS AND MAIN RESULTS: At day 0, participants with World Health Organization ordinal scale 5-7 had elevated ANC counts, compared with ordinal scale 4. In addition, the levels of neutrophil-associated biomarkers, inflammatory cytokines, and mediators of endothelial dysfunction at day 0 were increased in the participants who were ordinal scale 5-7 vs. ordinal scale 4. Randomization to fostamatinib compared with placebo resulted in a decrease in ANC and several neutrophil-associated biomarkers, pro-inflammatory cytokines, and mediators of endothelial dysfunction/tissue damage. This differential finding was also demonstrated in a subgroup of patients (n = 85) with a hypoinflammatory phenotype.
LIMITATIONS: Missing plasma samples and neutral phase 3 trial results.
CONCLUSIONS: Randomization to fostamatinib resulted in lower neutrophil counts and levels of circulating biomarkers in hospitalized patients with COVID-19; however, the observed impact of fostamatinib was modest compared with prior studies.