Survival for COVID-19 patients improves by Immune modulator drugs

A large randomized, placebo-controlled clinical trial led by the National Institutes of Health found that treating adults hospitalized with COVID-19 with infliximab or abatacept – drugs commonly used to treat certain autoimmune diseases – did not significantly improve clinical status or reduce deaths.

Some COVID-19 patients develop an immunological reaction in which their immune system secretes an excessive number of proteins, causing inflammation that can lead to ARDS, multiple organ failure, and other life-threatening consequences.

The ACTIV-1 Immune Modulators clinical trial was launched as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private initiative to see if certain drugs that help minimize the effects of an overactive immune response could speed recovery and reduce deaths in adults hospitalized with moderate to severe COVID-19.

Three sub-studies were included in the ACTIV-1 master protocol, each of which compared an immune modulator medication versus a placebo. This method allows for the simultaneous examination of multiple investigational drugs in a coordinated and efficient manner.

The trial was coordinated and overseen by the National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS), which received funding from the US Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response’s Biomedical Advanced Research and Development Authority (BARDA).

“These promising ACTIV-1 results demonstrate the collaborative power of public-private partnerships to accelerate therapeutic answers during this unprecedented global health crisis,” said Acting NIH Director Lawrence A. Tabak, D.D.S., Ph.D. “Working together, NIH and our ACTIV partners have brought to bear the best tools and clinical trial designs in our research arsenals. The innovative ACTIV model is bringing greater clarity to the search for effective, evidence-based COVID-19 treatments.”

In addition to the standard of therapy, which may include Gilead Sciences, Inc.’s remdesivir (Veklury), ACTIV-1 participants were randomly assigned to one of the immune modulator medications or placebo. Roughly 90% of the patients were given remdesivir, while about 85% were given dexamethasone.

Investigators kept track of participants’ clinical status and recorded it on a daily basis while they were in the hospital, using an eight-point scale that ranged from not hospitalized to death. The full report on these findings will be published in a peer-reviewed scientific publication in the fall of 2022, with a preprint available sooner.

In addition to the standard of therapy, which may include Gilead Sciences, Inc.’s remdesivir (Veklury), ACTIV-1 participants were randomly assigned to one of the immune modulator medications or placebo. Roughly 90% of the patients were given remdesivir, while about 85% were given dexamethasone.

In addition to the standard of therapy, which may include Gilead Sciences, Inc.’s remdesivir (Veklury), ACTIV-1 participants were randomly assigned to one of the immune modulator medications or placebo. Roughly 90% of the patients were given remdesivir, while about 85% were given dexamethasone.

Investigators kept track of participants’ clinical status and recorded it on a daily basis while they were in the hospital, using an eight-point scale that ranged from not hospitalized to death. The full report on these findings will be published in a peer-reviewed scientific publication in the fall of 2022, with a preliminary accessible later.

The following were the topline findings:

Participants who received infliximab (Remicade) showed a significant but not statistically significant improvement in the primary endpoint of time to recovery as determined by the day of discharge from the hospital when compared to placebo.

At 28 days, there were significant improvements in both the key secondary objectives of death and clinical status. The mortality rate for the 518 participants who received infliximab was 10.0 percent, compared to 14.5 percent for the 519 people who received placebo, resulting in a 40.5 percent reduced adjusted death rate.

In both moderately and severely ill patients, the relative improvement in mortality was similar. The infliximab group had a 43.8 percent higher chance of improving clinically than the placebo group.

Janssen Biotech, Inc., one of Johnson & Johnson’s Janssen Pharmaceutical Companies, developed and markets infliximab, which is given as a single dosage.

Participants who received abatacept (Orencia) showed a significant but not statistically significant improvement in the primary endpoint of time to recovery as determined by the day of discharge from the hospital when compared to placebo.

At 28 days, there were significant improvements in both the key secondary objectives of death and clinical status. The death rate for the 509 people who received abatacept was 11.0 percent, compared to 15.0 percent for the 513 participants who received placebo, resulting in a 37.4 percent reduced adjusted death rate.

In both moderately and severely ill patients, the relative improvement in mortality was similar.

The abatacept group had a 34.2 percent higher chance of improving clinically than the placebo group. Bristol Myers Squibb developed and markets Abatacept, which is given as a single dose.

Enrollment in the third sub-study assessing the investigational medication cenicriviroc was halted in September 2021, after an independent data and safety monitoring board (DSMB) advised that it be closed owing to ineffectiveness. AbbVie gave the cenicriviroc.

The findings will be shared with treatment guideline organizations and regulatory entities.

“When given in addition to standard of care treatments, like remdesivir and dexamethasone, infliximab and abatacept each offered a substantial reduction in mortality,” said the trial’s protocol chair, William G. Powderly, M.D., 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.”

The ACTIV-1 Immune Modulators clinical trial included 1,971 participants from October 2020 to December 2021 at 46 medical facilities in the United States and 23 medical facilities in Latin America. An independent DSMB examined the study on a regular basis, and no safety issues were raised during the experiment.

The Clinical and Translational Science Awards (CTSA) Program of the National Center for Advancing Translational Sciences (NCATS) and the Trial Innovation Network were essential in attracting participants in the United States.

“More than half of the CTSA Program sites contributed their infrastructure and expertise to speed completion of this trial,” said Joni L. Rutter, Ph.D., acting director of NCATS. “This collaborative and efficient multinational platform trial design streamlined our ability to urgently and robustly test promising therapies for treating people hospitalized with COVID-19.”