NEW YORK (Reuters Health) – For adults hospitalized with COVID-19, combining remdesivir with a highly concentrated solution of SARS-CoV-2 neutralizing antibodies derived from patients who have recovered from the infection was not more effective than remdesivir alone in the ITAC trial.
The hope of the study was that adding SARS-CoV-2 hyperimmune intravenous immunoglobulin (hIVIG) to a remdesivir regimen would “give the immune system a boost to help suppress the virus early in the course of hospitalization,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID) said in a news release.
“Unfortunately, the ITAC trial demonstrated that this strategy did not improve the health of adults hospitalized with COVID-19 and may be harmful for a certain subset of patients. Studies testing this strategy in non-hospitalized adults earlier in the course of infection are underway,” Dr. Fauci said.
The international trial enrolled 593 adults hospitalized with COVID-19 symptoms for up to 12 days who did not have life-threatening organ dysfunction or organ failure. They were randomly assigned to receive a single infusion of anti-coronavirus hIVIG or saline placebo, in addition to remdesivir plus standard supportive care.
Compared with remdesivir alone, treatment with hIVIG plus remdesivir did not lead to better health status seven days after starting treatment (adjusted odds ratio, 1.06; 95% CI, 0.77 to 1.45), Dr. Mark Polizzotto with the Australian National University, in Canberra, and colleagues report in The Lancet.
Patients who received hIVIG with remdesivir also had no improvement in other clinical outcomes during the 28-day follow-up period compared to those who received remdesivir alone.
“Overall, these findings indicate that hIVIG confers no clinical benefit for hospitalized patients with COVID-19,” the researchers write.
Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18.6% vs. 9.5%; P=0.002).
There was no overall difference in safety at seven days for patients who received hIVIG plus remdesivir compared with those who received remdesivir alone.
However, in pre-specified subgroup analysis, patients given hIVIG who had SARS-CoV-2-neutralizing antibodies at baseline were more apt to suffer adverse “safety events” at day seven than peers without SARS-CoV-2-neutralizing antibodies at baseline.
“Elucidating the mechanisms of any possible harm of hIVIG in neutralizing antibody-positive individuals will require further study,” the study team says.
They caution that while the ITAC trial found no evidence of clinical benefit of hIVIG in hospitalized patients when added to remdesivir and standard of care, “a potential role for hIVIG might still be found in earlier disease stages of COVID-19 or special populations. As with other passive immunotherapies it is possible that a population treated very early in the onset of disease might benefit, as might groups with persistent failure to mount humoral immune responses to infection.”
The authors of a linked commentary in The Lancet say this “well-performed randomized controlled study is an important addition to the existing literature, unravelling the role of passive immunization for COVID-19 patients, in particular regarding dose. However, more questions have been raised regarding the safety aspect, which needs more research for better understanding.”
The ITAC trial was funded by the National Institutes of Health.
SOURCE: https://bit.ly/3AG7nUp https://bit.ly/3G7bdGZ The Lancet, online January 27, 2022.
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