Review: Remdesivir improves recovery, reduces mortality of COVID-19 patients

A systematic review of randomized controlled trials (RCTs) has confirmed the potential of remdesivir in improving recovery and reducing serious adverse events (AEs), as well as mortality and time to clinical improvement, but not hospital length of stay, in coronavirus disease (COVID-19) patients.

“For adults not receiving mechanical ventilation or extracorporeal membrane oxygenation (ECMO), a 5-day course of remdesivir may provide similar benefits to and fewer harms than a 10-day course,” the researchers said.

English-language RCTs of remdesivir treatments for adults with suspected or confirmed COVID-19 were searched from several databases, tables of contents of journals, and US Food and Drug Administration and company websites from 1 January through 31 August 2020.

A single reviewer abstracted data and assessed risk of bias, which were verified by a second reviewer. Certainty of evidence was evaluated using Grading of Recommendations Assessments, Development and Evaluation (GRADE) methods.

Four RCTs met the eligibility criteria. Compared with placebo, remdesivir significantly improved recovery in adults with severe COVID-19 (absolute risk difference [ARD] range, 7–10 percent) and was associated with a small reduction in mortality (ARD range, –4 percent to 1 percent) and a shorter time to recovery or clinical improvement. [Ann Intern Med 2020;doi:10.7326/M20-5752]

Remdesivir, however, showed little to no effect on hospital length of stay. The antiviral agent also reduced serious AEs by a moderate amount (ARD range, –6 percent to –8 percent).

Among hospitalized patients not requiring mechanical ventilation, a 5-day remdesivir course, compared with a 10-day course, reduced mortality, increased recovery or clinical improvement by small to moderate amounts, shortened time to recovery, and lessened serious AEs. Recovery did not vary by age, sex, symptom duration, or disease severity.

“However, among patients whose symptoms worsen and who require mechanical ventilation or ECMO on day 5 of the remdesivir course, continuing treatment through 10 days may be beneficial versus discontinuing it on day 5,” the researchers noted.

For those with moderate COVID-19, a 5-day course compared with standard of care was associated with small reductions in mortality and serious AEs and a greater number of patients having clinical improvement at day 11. Notably, a 10-day course was not more effective than 5 days or standard of care. [JAMA 2020;324:1048-1057]

“Our findings are generally in line with prior reviews, although none included the trial of remdesivir in patients with moderate COVID-19, and outcomes reported in prior reviews were limited,” the researchers said. [J Med Virol 2020;doi:10.1002/jmv.26443; Eur J Clin Invest 2020:e13383; Virus Res 2020;288:198137; BMJ 2020;370:m2980; www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management]

“Our living review uses methods specifically derived for continual updating and is intended, in part, to inform the work of the American College of Physicians Scientific Medical Policy Committee,” they added.

This systematic review was limited by low-certainty evidence with few published trials, including one preliminary report and two open-label trials. Trials also excluded pregnant women and adults with severe kidney or liver disease.

“New evidence will be incorporated using living review methods and may alter these conclusions,” the researchers said.