Bethesda, MD—Two drugs used to treat specific autoimmune diseases improved the clinical status and reduced mortality in patients hospitalized with COVID-19, although they did not significantly shorten the time to recovery, according to a large randomized, placebo-controlled clinical trial led by the National Institutes of Health (NIH).
The drugs that help minimize the effects of an overactive immune system—infliximab and abatacept—were tested because in some COVID-19 patients, the immune system causes excessive inflammation that can lead to acute respiratory distress syndrome, multiple organ failure, and other life-threatening complications.
As part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private initiative, the NIH launched the ACTIV-1 Immune Modulators clinical trial. Its master protocol included three substudies to test an immune modulator drug compared with a placebo.
ACTIV-1 participants were randomly assigned to one of the immune modulator drugs or placebo in addition to the standard of care, which might include Veklury (remdesivir) supplied by Gilead Sciences, Inc. Approximately 90% received remdesivir, and approximately 85% received dexamethasone.
The study is expected to be published in the fall, with a preprint available sooner. The NIH reported the topline results as the following:
• Compared with placebo, participants receiving Remicade (infliximab) displayed a strong, but not statistically significant, improvement in the primary endpoint of time to recovery as measured by day of discharge from hospital. On the other hand, researchers observed substantial improvements for both key secondary endpoints of mortality and clinical status at 28 days. The 518 participants receiving infliximab had a death rate of 10.0%, compared with 14.5% for the 519 participants receiving placebo, resulting in 40.5% lower adjusted odds of dying. Both moderately and severely ill participants demonstrated relative improvement in mortality. At the same time, patients in the infliximab group had a 43.8% better odds of clinical improvement than those in the placebo group. Infliximab, which was given as a single dose, was developed and is marketed by Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson.
• Participants receiving Orencia (abatacept) compared with placebo demonstrated a strong, but not statistically significant, improvement in the primary endpoint of time to recovery as measured by day of discharge from the hospital. The study team reports substantial improvements for both key secondary endpoints of mortality and clinical status at 28 days, however. The 509 participants receiving abatacept had a death rate of 11.0%, compared with 15.0% for the 513 participants receiving placebo, resulting in 37.4% lower adjusted odds of dying, with the relative improvement in mortality being similar in both moderately and severely ill participants. The abatacept group participants had a 34.2% better odds of clinical improvement than those in the placebo group. Abatacept, which was given as a single dose, was developed and is marketed by Bristol Myers Squibb.
• Enrollment into the third substudy evaluating the investigational medicine cenicriviroc was stopped in September 2021 after an independent data and safety monitoring board recommended closing it due to lack of efficacy, the NIH noted. Cenicriviroc was provided by AbbVie.
"When given in addition to standard of care treatments, like remdesivir and dexamethasone, infliximab and abatacept each offered a substantial reduction in mortality," stated William G. Powderly, MD, the trial's protocol chair and director of the Institute for Clinical and Translational Sciences and co-director of the Division of Infectious Diseases at Washington University School of Medicine in St. Louis. "These drugs could potentially add to the therapeutic options available for the treatment of patients hospitalized with COVID-19."
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