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

Catharine I. Paules, Jing Wang, Kay M. Tomashek, Tyler Bonnett, Kanal Singh, Vincent C. Marconi, Richard T. Davey, David C. Lye, Lori E. Dodd, Otto O. Yang, Constance A. Benson, Gregory A. Deye, Sarah B. Doernberg, Noreen A. Hynes, Robert Grossberg, Cameron R. Wolfe, Seema U. Nayak, William R. Short, Jocelyn Voell, Gail E. PotterRekha R. Rapaka

Research output: Contribution to journalArticlepeer-review


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 ¼ 999; 85% U.S. participants). Intervention: Baricitinib þ remdesivir versus placebo þ 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 þ remdesivir was associated with reduced risk for death (hazard ratio [HR], 0.38 [95% CI, 0.16 to 0.86]; P ¼ 0.020), decreased progression to IMV or death (HR, 0.57 [CI, 0.35 to 0.93]; P ¼ 0.024), and improved recovery rate (HR, 1.53 [CI, 1.16 to 2.02]; P ¼ 0.002) compared with placebo þ remdesivir. After 5 days, participants receiving baricitinib þ 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.

Original languageEnglish (US)
Pages (from-to)343-352
Number of pages10
JournalAnnals of internal medicine
Issue number3
StatePublished - Mar 1 2024

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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