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.
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