Dr. Rose
Clinical question: What immunomodulatory drugs should we use in hospitalized patients with COVID-19 in addition to corticosteroids?
Background: Inflammation is a key driver of morbidity and mortality in patients with COVID-19. The RECOVERY trial first demonstrated the efficacy of corticosteroids in hospitalized patients with COVID-19 who required supplemental oxygen. Subsequent trials have shown additive benefit in select patients for the IL-6 inhibitors tocilizumab (RECOVERY; REMAP-CAP) and sarilumab (REMAP-CAP), as well as with the Janus kinase inhibitors baricitinib (ACTT-2; COV-BARRIER; RECOVERY) and tofacitinib (STOP-COVID), leading to their inclusion in national guidelines. Other unique immunomodulators have not shown clear benefits. Little data exist for adding two or more immunomodulatory agents to corticosteroids.
Study design: Multicenter, randomized, double-blinded, placebo-controlled trial
Setting: Hospitalized patients (including ICU patients) in the U.S. and Latin America
Synopsis: 1,971 hospitalized adults with COVID-19 pneumonia between October 2020 and December 2021 (Omicron wave) were randomized to receive abatacept (T-cell inhibitor), cenicriviroc (monocyte and macrophage inhibitor), infliximab (TNF-alpha inhibitor), or placebo, in addition to standard of care. More than 90% of patients received corticosteroids and remdesivir, but fewer than 5% received IL-6 or Janus kinase inhibitors.
No agents significantly improved the primary outcome of median time to recovery. Abatacept (11.0% versus 15.1% (OR, 0.62; CI, 0.41-0.94) and infliximab (10.1% versus 14.5% (OR, 0.59; CI, 0.39-0.90), but not cenicriviroc (13.8% versus 11.9% (OR, 1.18; CI 0.72-1.94), improved all-cause mortality at day 28, a pre-specified key secondary endpoint.
This study further supports adding another immunomodulatory agent to corticosteroids when treating hospitalized patients with COVID-19 pneumonia. Which agent is best and if multiple agents should be used remains unknown. Stronger evidence supports the use of either IL-6 inhibitors or Janus kinase inhibitors; abatacept or infliximab are unlikely to become recommended on par with these treatments.
Bottom line: Abatacept and infliximab should not replace IL-6 or Janus kinase inhibitors as the recommended non-corticosteroid immunomodulators for treating hospitalized patients with COVID-19 pneumonia.
Citation: O’Halloran JA, Ko ER, et al. Abatacept, cenicriviroc, or infliximab for treatment of adults hospitalized with COVID-19 pneumonia: A randomized clinical trial. JAMA. 2023;330(4):328-39.
Dr. Rose is a hospitalist at Johns Hopkins Hospital and an assistant professor of medicine and pediatrics at Johns Hopkins University School of Medicine in Baltimore. Disclosure: He received consulting fees from 20/20 GeneSystems regarding COVID-19 testing.