Immune modulator drugs improves survival for people hospitalised with COVID-19

A large randomised, placebo-controlled clinical trial led by the National Institutes of Health (NIH) has shown that treating adults hospitalised with COVID-19 with infliximab or abatacept – drugs widely used to treat certain autoimmune diseases – did not significantly shorten time to recovery, but substantially improved clinical status and reduced deaths.

Some COVID-19 patients experience an immune response in which the immune system unleashes excessive amounts of proteins that trigger 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, NIH launched the ACTIV-1 immune modulators clinical trial to determine if certain drugs that help minimise the effects of an overactive immune response could speed recovery and reduce deaths in adults hospitalised with moderate-to-severe COVID-19. The ACTIV-1 master protocol included three sub-studies; each one tested an immune modulator drug as compared to a placebo. This approach allowed for coordinated and efficient evaluation of multiple investigational agents simultaneously, NIH said in a statement.

NIH’s National Center for Advancing Translational Sciences (NCATS) coordinated and oversaw the trial with funding from the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response, it further said.

According to the statement, ACTIV-1 participants were randomly assigned to one of the immune modulator drugs or placebo in addition to the standard of care, which may include remdesivir (Veklury) supplied by Gilead Sciences. About 90 per cent received remdesivir, and about 85 per cent received dexamethasone.

Investigators monitored participants and recorded their clinical status daily while hospitalised, according to an eight-point scale ranging from not hospitalised with no limitations on activities to death. The full report on these data in a peer-reviewed scientific journal is expected in fall of 2022, and a preprint will be available sooner, mentioned the statement.

Compared to placebo, participants receiving infliximab (Remicade) displayed a strong but not statistically significant improvement in the primary endpoint of time to recovery as measured by day of discharge from hospital. Substantial improvements for both key secondary endpoints of mortality and clinical status at 28 days were observed. The 518 participants receiving infliximab had a death rate of 10 per cent, compared to 14.5 per cent for the 519 participants receiving placebo, resulting in 40.5 per cent lower adjusted odds of dying. The relative improvement in mortality was similar in both moderately- and severely-ill participants. People in the infliximab group had 43.8 per cent 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, according to the statement.

It also noted that compared to placebo, participants receiving abatacept (Orencia) displayed a strong but not statistically significant improvement in the primary endpoint of time to recovery as measured by day of discharge from hospital. Substantial improvements for both key secondary endpoints of mortality and clinical status at 28 days were observed. The 509 participants receiving abatacept had a death rate of 11 per cent, compared to 15 per cent for the 513 participants receiving placebo, resulting in 37.4 per cent lower adjusted odds of dying. The relative improvement in mortality was similar in both moderately and severely ill participants. People in the abatacept group had 34.2 per cent 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 sub-study evaluating the investigational medicine cenicriviroc was stopped in September 2021 after an independent Data and Safety Monitoring Board (DSMB) recommended closing it due to lack of efficacy. Cenicriviroc was provided by AbbVie. The results will be made available to treatment guideline groups and regulatory bodies, the statement further said.