Which Immunomodulator for Severe COVID-19?

Severe COVID-19 results from a dysregulated immune response to SARS-CoV-2, and steroids, baricitinib (a Janus kinase inhibitor), and tocilizumab (an IL-6 inhibitor) are all effective therapies. To test the efficacy of additional immunomodulators under a master protocol with a shared (but not identical) placebo group, investigators randomized 1971 patients hospitalized with COVID-19 pneumonia to receive abatacept (mitigates T-cell response), cenicriviroc (reduces monocyte and macrophage function), infliximab (inhibits tumor necrosis factor α), or placebo. Patients received background standard of care that included remdesivir and steroids.

Median time to recovery by day 28 (the primary outcome) did not differ between placebo recipients (8–9 days) versus those who received abatacept (9 days), cenicriviroc (8 days), or infliximab (8 days). Because the prespecified primary endpoint was not met, the following secondary endpoint was not deemed statistically significant: day 28 all-cause mortality (11.0% [abatacept] and 15.1% [placebo]; 10.1% [infliximab] and 14.5% [placebo]). No difference was observed in all-cause mortality between cenicriviroc and placebo recipients. Except for three serious infusion reactions in abatacept recipients, safety events were comparable among groups (including incidence of secondary infections).