A Risk Profile Using Simple Hematologic Parameters to Assess Benefits From Baricitinib in Patients Hospitalized With COVID-19: A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-2.
Ann Intern Med
; 177(3): 343-352, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38408357
ABSTRACT
BACKGROUND:
The ACTT risk profile, which was developed from ACTT-1 (Adaptive COVID-19 Treatment Trial-1), demonstrated that hospitalized patients with COVID-19 in the high-risk quartile (characterized by low absolute lymphocyte count [ALC], high absolute neutrophil count [ANC], and low platelet count at baseline) benefited most from treatment with the antiviral remdesivir. It is unknown which patient characteristics are associated with benefit from treatment with the immunomodulator baricitinib.OBJECTIVE:
To apply the ACTT risk profile to the ACTT-2 cohort to investigate potential baricitinib-related treatment effects by risk quartile.DESIGN:
Post hoc analysis of ACTT-2, a randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov NCT04401579).SETTING:
Sixty-seven trial sites in 8 countries.PARTICIPANTS:
Adults hospitalized with COVID-19 (n = 999; 85% U.S. participants). INTERVENTION Baricitinib+remdesivir versus placebo+remdesivir. MEASUREMENTS Mortality, progression to invasive mechanical ventilation (IMV) or death, and recovery, all within 28 days; ALC, ANC, and platelet count trajectories.RESULTS:
In the high-risk quartile, baricitinib+remdesivir was associated with reduced risk for death (hazard ratio [HR], 0.38 [95% CI, 0.16 to 0.86]; P = 0.020), decreased progression to IMV or death (HR, 0.57 [CI, 0.35 to 0.93]; P = 0.024), and improved recovery rate (HR, 1.53 [CI, 1.16 to 2.02]; P = 0.002) compared with placebo+remdesivir. After 5 days, participants receiving baricitinib+remdesivir had significantly larger increases in ALC and significantly larger decreases in ANC compared with control participants, with the largest effects observed in the high-risk quartile.LIMITATION:
Secondary analysis of data collected before circulation of current SARS-CoV-2 variants.CONCLUSION:
The ACTT risk profile identifies a subgroup of hospitalized patients who benefit most from baricitinib treatment and captures a patient phenotype of treatment response to an immunomodulator and an antiviral. Changes in ALC and ANC trajectory suggest a mechanism whereby an immunomodulator limits severe COVID-19. PRIMARY FUNDING SOURCE National Institute of Allergy and Infectious Diseases.
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Base de dados:
MEDLINE
Assunto principal:
Purinas
/
Pirazóis
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Sulfonamidas
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Azetidinas
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COVID-19
Limite:
Adult
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Humans
Idioma:
En
Revista:
Ann Intern Med
Ano de publicação:
2024
Tipo de documento:
Article