By Jonathan Springston, Editor, Relias Media

It appears researchers are prepared to remove interferon from the list of possible COVID-19 therapeutics, as it showed little clinical benefit for hospitalized patients, according to the results of a recently published paper.

Previous laboratory studies indicated SARS-CoV-2 interferes with the body’s normal production of type 1 interferons, which help the immune system fight viruses and other pathogens. The authors of the ACTT-3 trial, backed by the National Institute of Allergy and Infectious Diseases, speculated about the potential for subcutaneous interferon beta-1a, a multiple sclerosis medication, to help COVID-19 patients recover. They also wanted to learn how interferon might work when combined with remdesivir, an FDA-approved COVID-19 therapeutic for those hospitalized with the disease.

ACTT-3 was a double-blind, placebo-controlled, randomized trial conducted between August and December 2020. Investigators recruited 969 adults at dozens of sites across five countries, including the United States. Eligible subjects were age 18 years or older, hospitalized with COVID-19, and met criteria suggestive of lower respiratory tract infection. Patients were randomly assigned (1:1) to receive an intravenous, 200 mg loading dose of remdesivir on day 1, followed by a 100 mg maintenance dose administered each day for up to nine days and as many as four doses of 44 μg interferon beta-1a (known as the interferon beta-1a group plus remdesivir group; n = 487) or placebo (known as the placebo plus remdesivir group; n = 482) administered subcutaneously every other day.

The authors observed time to recovery remained a median of five days for patients in both groups. All patients also demonstrated similar clinical improvement at day 15. More troubling, researchers had to modify the study design after one month to exclude patients on high-flow oxygen and mechanical ventilation after finding a higher rate of severe adverse outcomes for those on interferon.

In their discussion, the ACTT-3 authors pointed to five previous studies of interferon beta in hospitalized adult patients with COVID-19, noting three of those demonstrated some efficacy. Although they theorized why there were promising results in those three studies, the ACTT-3 authors underlined the fact none of the five previous trials were double-blinded, which can lead to bias in treatment selection, patient assessment, and patient enrollment. For now, considering the results of their own work, the ACTT-3 authors do not recommend subcutaneous interferon beta-1a treatment for patients hospitalized with COVID-19.

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