FDA Limits Use of Convalescent Plasma as Covid-19 Treatment

“The purpose of the update is that convalescent plasma can be better used by those who will benefit,” said Peter Marks, director of the FDA’s Center for Biological Research and Evaluation. “It is being used a little more indiscriminately.”

Dr. Claudia Cohn, medical director at AABB, an organization representing the transfusion medicine community, said the group plans to issue tentative recommendations on convalescent plasma later this month. “There are so many studies that come to different conclusions,” she said. “It is not clean, it is not black and white.”

Dr. Marks said the FDA made its decision after evaluating the results of several recent studies. Some have shown benefits of convalescent plasma, the antibody-containing fluid derived from the blood of people who have recovered from Covid-19. Others have shown no benefit.

Two clinical trials of convalescent plasma for hospitalized patients were closed last month after the researchers said there appeared to be no benefit. Three studies involving hospitalized patients recently reported some benefit for plasma, but only when administered to patients shortly after admission. Yet another trial showed that elderly outpatients who received plasma shortly after experiencing symptoms were less likely to develop serious illnesses.

Arturo Casadevall, president of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, called the FDA decision “a step forward”. He said: “Doctors in the United States, for the first time, will receive guidance on when and how to use” convalescent plasma.

Dr. Casadevall is a co-founder of the Convalescent Plasma Project Covid-19, which helped organize a nationwide expanded access study to convalescent plasma that began last April.

Despite the contradictory findings, convalescent plasma remains in demand – in part because there are few effective treatments for Covid-19 and many people remain unvaccinated. Since the FDA issued the emergency authorization last August, the blood industry has distributed an average of about 20,600 units of convalescent plasma per week to hospitals across the country, according to the American Red Cross.

The FDA’s previous decision to authorize convalescent plasma for hospitalized Covid-19 patients was based largely on the results of an expanded access program sponsored by the agency, through which more than 72,000 patients received plasma. For a study published last month in the New England Journal of Medicine, the researchers analyzed data from 3,000 of these patients and reported an apparent survival benefit among hospitalized patients who were not on mechanical ventilation and who received plasma containing high concentrations of antibodies.

But many scientists have expressed skepticism about this finding, saying that expanded access studies lack the scientific rigor of traditional testing because they lack a control group to compare any apparent effects.

Dr. Marks of the FDA said the convalescent plasma clearance “could have been treated much better. It had to do with the sense of urgency that everyone is feeling. I cannot blame anyone for feeling a sense of urgency. “

Dr. Marks also said that the data can be confusing. Each unit of convalescent plasma is unique, reflecting the immune response of the recovered patient who donated it. It took time to find the best way to measure antibodies in a unit, he added.

The US is not the only government trying to establish reliable guidelines on the use of convalescent plasma. In Argentina, a study on elderly outpatients published last month in the New England Journal of Medicine contributed current recommendations for treating elderly patients with Covid-19 early in the course of their disease. “Plasma supplies are not infinite and public health authorities invariably face difficult decisions,” said study co-author Dr. Fernando Polack of Fundación Infant in Buenos Aires. “In any of these decisions, data-based guidelines are necessary and are the best way for doctors to feel comfortable when facing individual cases.”

Louis M. Katz, medical director of the Mississippi Valley Regional Blood Center in Davenport, Iowa, which supplies blood products to more than 120 hospitals, said the evidence supporting the use of convalescent plasma in hospitalized patients is weak. “I think there is data that it works early,” he said. “As you move towards increasingly sick people, the evidence becomes increasingly blurred.”

In an editorial accompanying the New England Journal of Medicine article on the expanded access study in the U.S., Dr. Katz said that convalescent plasma should be used only in patients early in the course of the disease. The problem with this suggestion, he added later, is that the FDA’s emergency use authorization still only covers hospitalized patients, who tend to show up at the hospital when they have been sick the longest.

The treatment of patients with Covid-19 who are beginning to show symptoms presents its own challenges. “Logistically, it is very difficult to treat patients earlier,” said Dr. Katz. “It is difficult to transfuse a lot of plasma in outpatients.”

Dr. Marks said a large National Institutes of Health study is underway to test convalescent plasma in people with Covid-19 who are sick enough to go to the emergency room but are not admitted to the hospital, as are other trials randomized clinical trials of plasma in outpatients. “As long as we do not have this data, we will maintain authorization for inpatients,” he said. “We will refine it again if appropriate. This is a scarce resource. “

Write to Amy Dockser Marcus at [email protected]