IFN β-1a Plus Remdesivir Linked to Worse Outcomes in Severe COVID-19 Pneumonia

Combining interferon beta-1a (IFN β-1a)  with remdesivir is not superior to remdesivir alone in treating hospitalized patients with COVID-19 pneumonia, according to the results of a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04492475) reported recently in The Lancet Respiratory Medicine. The researchers found that patients had inferior outcomes more often after treatment with interferon beta-1a compared with patients given placebo, but the outcomes were worse for those who needed high-flow oxygen at baseline.

The functional impairment of IFN has been associated with the pathogenesis and severity of COVID-19. Earlier studies showed an impaired induction of type 1 interferons following COVID-19 infection, and hospitalized patients with COVID-19 have displayed a downregulated IFN response, which is associated with more severe disease. Therefore, earlier data suggested that administering IFN β-1a in combination with remdesivir could be a potential therapeutic option.

In the current study, researchers at 63 hospitals across 5 countries (Japan, Mexico, Singapore, South Korea, and the US) randomly assigned 969 participants to 2 groups. The first group received intravenous remdesivir as a 200-mg loading dose on day 1, followed by a 100-mg maintenance dose administered daily for up to 9 days, along with up to 4 doses of 44 μg IFN β-1a administered subcutaneously every other day. The second group received remdesivir plus placebo. The primary outcome was time to recovery, defined as the first day that a patient reached a category 1, 2, or 3 score on the 8-category ordinal scale within 28 days.

The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI, 3%-7%) in the IFN β-1a plus remdesivir group but only 3% (95% CI, 2%-6%) in the placebo plus remdesivir group (hazard ratio, 1.33 [95% CI, 0.69-2.55]; P =.39). Patients who did not need high-flow oxygen at baseline were more likely to have at least 1 related adverse event in the IFN β-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients requiring high-flow oxygen at baseline, however, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the IFN β-1a plus remdesivir group, whereas 13 (39%) of 33 had an adverse event and 8 (24%) had a serious adverse event in the placebo plus remdesivir group.

The study was not designed to assess the efficacy of interferon beta-1a in patients with early-stage or mild disease who do not require hospitalization. “IFN is suppressed early in SARS-CoV-2 infection, and early treatment could still be beneficial and needs to be evaluated in rigorous studies,” the researchers concluded.

Reference

Kalil AC, Mehta AK, Patterson TF, et al. Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021;9(12):1365-1376. doi:10.1016/S2213-2600(21)00384-2