The safety of an anti-coronavirus hyperimmune intravenous immunoglobulin may be influenced by whether an individual is able to naturally generate SARS-CoV-2-neutralizing antibodies.
A combination of remdesivir with a highly concentrated solution of antibodies that neutralize SARS-CoV-2 was not found to be more effective than remdesivir monotherapy in treating adult patients hospitalized with COVID-19, according to the results of a multinational phase 3 trial published recently in The Lancet.
The safety of the antibody solution, an anti-coronavirus hyperimmune intravenous immunoglobulin (hIVIG), may be influenced by whether an individual is able to naturally generate SARS-CoV-2-neutralizing antibodies prior to administration of the treatment, according to the study authors. The trial, called the Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC), was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
“In our quest to find safe and effective treatments for COVID-19, we had hoped that adding anti-coronavirus hIVIG to a remdesivir regimen would give the immune system a boost to help suppress the virus early in the course of hospitalization,” said NIAID Director Anthony S. Fauci, MD, in a press 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.”
The antibodies in hIVIG were derived from the liquid portion of plasma from healthy donors who previously recovered from COVID-19. The antibodies were highly purified and concentrated, which allowed the anti-coronavirus hIVIG to contain several times more SARS-CoV-2 neutralizing antibodies than what is frequently found in blood from donors who have recovered from COVID-19, according to the investigators.
Remdesivir, a broad-spectrum antiviral previously approved by the FDA, is recommended for treating certain patients with COVID-19 based on data from randomized clinical trials. The ITAC study included approximately 600 hospitalized patients 18 years of age or older who had COVID-19 symptoms for up to 12 days and who did not have life-threatening organ dysfunction or organ failure.
The patients were randomized to receive infusions of anti-coronavirus hIVIG and remdesivir or a placebo and remdesivir. The patients and the ITAC investigators did not know who received which treatment regimen until the trial was over. Only the pharmacists who prepared the infusions had that information. All patients were administered supportive care that reflects local practice and national guidelines, according to the study.
The ITAC investigators sought to compare the health status of patients 7 days following the initiation of treatment with hIVIG plus remdesivir versus the health status of patients 7 days after the initiation of treatment with remdesivir monotherapy.
The primary endpoint was an ordinal outcome with 7 mutually exclusive categories that included no limiting symptoms due to COVID-19 and death. Safety of hIVIG was assessed at day 7 with a composite outcome that included death, serious adverse events (AEs), such as organ failure and serious infections, and severe AEs that prevented performing basic functions.
The ITAC investigators found that participants who received hIVIG plus remdesivir did not have better health status 7 days after starting treatment compared with those administered remdesivir monotherapy. Further, patients administered hIVIG plus remdesivir showed no improvement in other clinical outcomes during the 28-day follow-up period compared to patients administered remdesivir monotherapy.
There was no overall difference found in safety at day 7 for patients administered hIVIG plus remdesivir compared to patients administered remdesivir monotherapy. The ITAC investigators conducted a pre-specified subgroup analysis of safety among participants who developed SARS-CoV-2 neutralizing antibodies prior to administration of hIVIG. In these patients, the likelihood of a worse safety outcome at day 7 was found to be 1.6 times higher for patients administered hIVIG than for those who did not receive the treatment, but this difference was no longer found at day 28, according to the study.
Hyperimmune intravenous immunoglobulin does not improve outcomes for adults hospitalized with COVID-19. National Institute of Allergy and Infectious Diseases. News release. January 27, 2022. https://www.eurekalert.org/news-releases/941401. Accessed February 17, 2022.