Hematologic parameters pinpointed a group of hospitalized patients who were most likely to benefit from baricitinib.

In the ACTT-2 study, patients hospitalized with COVID-19 who received remdesivir plus the immunomodulator baricitinib recovered sooner than those who received remdesivir alone (NEJM JW Infect Dis Dec 17 2020 and N Engl J Med Mar 4 2021; 384:795) Now, investigators report a post hoc analysis of ACTT-2 to assess whether a risk profile based on hematologic parameters (low absolute lymphocyte count, high absolute neutrophil count, and low platelet count at baseline) identifies a group most likely to benefit from baricitinib. This “ACTT risk profile” was derived from the ACTT-1 study, in which the profile predicted risk for clinical progression among hospitalized patients.

A total of 999 participants from ACTT-2 were included. Among participants at high risk for progression based on ACTT risk profile, baricitinib plus remdesivir was associated with lower mortality and better clinical outcomes than placebo plus remdesivir, even after adjustment for baseline oxygen requirements. Participants who received baricitinib had more-favorable changes in their hematologic parameters than those who received placebo.

COMMENT

Guidelines recommend adding baricitinib to dexamethasone in patients hospitalized with COVID-19 who have rapidly increasing oxygen requirements or who need high-flow oxygen, non-invasive ventilation, or mechanical ventilation. The current study finds that hematologic biomarkers provide information on which patients are most likely to benefit from baricitinib; it also highlights the need for discovering and incorporating patient-specific characteristics that go beyond oxygen requirement in making treatment decisions. However, because ACTT-2 did not include participants who received glucocorticoids for COVID-19 — now the standard of care for hospitalized patients requiring oxygen — we need more information on performance of biomarker-based approaches in patients receiving current therapies.