Hyperimmune immunoglobulin IV No help in severe cases of COVID

Hyperimmune intravenous immunoglobulin (hIVIG) added to standard of care, including remdesivir (Veklury), did not improve clinical outcomes in hospitalized patients with severe COVID-19, according to a randomized trial.

People who received hIVIGs had no better odds of a better clinical outcome at day 7 than those who received placebo (adjusted OR 1.06, 95% CI 0.77-1.45), reported Mark Polizzotto, MD, of the Australian National University in Canberra, and his colleagues in the ITAC group.

The composite safety results were similar between hIVIG and placebo at day 28 (HR 0.79, 95% CI 0.57-1.11), the authors wrote in The Lancet.

The risk of an adverse event was higher in antibody-positive hIGV recipients (26.3% versus 16.4%; OR 2.21, 95% CI 1.14-4.29) and lower in those who were antibody negative (22.7% vs. 34.3%; OR 0.51, 95% CI 0.29-0.90; P=0.001 for the interaction), depending on the results.

Polizotto’s team speculated that this antibody status may have played a role in the negative outcome of their study.

“Antibody therapy may not benefit patients who have already developed an immune response,” they wrote. “Thus, the null result overall could reflect the balance between a positive response in the antibody-negative subgroup and a neutral or unfavorable response in the antibody-positive subgroup.”

“In our quest to find safe and effective treatments for COVID-19, we had hoped that adding an anti-coronavirus hIVIG to a regimen of remdesivir would give the immune system a boost to help suppress the virus. early in hospitalization,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, which helped fund the study, said in a report. “Unfortunately, the ITAC trial demonstrated that this strategy…may be harmful to a certain subset of patients.”

Fauci added that studies are continuing to test this treatment in non-hospitalized adults earlier in the course of infection.

the ITAC The phase III trial was conducted in 63 hospitals in 11 countries, including the UK and the US, from October 2020 to February 2021. Participants included adults hospitalized with COVID who had symptoms for 12 days or less. They were randomized 1:1 to receive hIVIG or saline placebo.

The modified intent-to-treat cohort was divided into 295 people in the hIGI group and 284 in the placebo group. The average age was 59 years old and 56% of the participants were Caucasian. There were more women in the hIVIG group (49%) than in the placebo group (37%), Polizzotto’s team noted.

The median time from symptom onset to randomisation was 8 days, and 38% received supplemental or high-flow oxygen. During or before trial randomization, 96% received remdesivir, 56% corticosteroids, and 61% a prophylactic dose of heparin.

The primary endpoint was a seven-domain ordinal score based on the patient’s clinical status on day 7.

Looking at safety, hIVIG participants had excess infusion reactions (19% versus 10% for placebo, P=0.002) and Grade 3 or worse adverse reactions (6% vs 1%, P=0.012).

Most safety events were due to respiratory failure. There were 18 deaths in the hIVIG group and 22 deaths in the placebo group through Day 28 (6% versus 8%, respectively).

Data limitations include a sample size that may have been too small to detect a smaller treatment effect or identify certain clinical subgroups that might benefit from treatment.

“A lesson for COVID-19 and future pandemics is that there is no evidence of efficacy for convalescent plasma or HIVIg in hospitalized patients,” Polizotto’s group nevertheless concluded.