Remdesivir reduced mortality in COVID-19 inpatients who required no or conventional oxygen, but its effects on sicker patients are still uncertain, according to a new review.
The systematic review and meta-analysis used individual-patient data from randomized controlled trials of remdesivir in adult patients hospitalized with COVID-19 around the world. The researchers found nine trials eligible for inclusion and were able to obtain individual data for eight of them, covering 10,480 patients, all recruited between Feb 6, 2020, and April 1, 2021. Results of the analysis were published by The Lancet Respiratory Medicine on Feb. 21.
On the primary outcome of 28-day mortality, rates were 12.5% in the remdesivir group versus 14.1% in the no-remdesivir group (adjusted odds ratio [aOR], 0.88 [95% CI, 0.78 to 1.00]; P=0.045). The effect differed by respiratory support at baseline. Among patients on ventilation or high-flow oxygen, 30.0% on remdesivir died compared with 28.5% assigned to no remdesivir (aOR, 1.10 [95% CI, 0.88 to 1.38]; low-certainty evidence), while among those on no or low-flow oxygen, the mortality rates were 9.1% and 11.2%, respectively (aOR, 0.80 [95% CI, 0.70 to 0.93]; high-certainty evidence). No effect was found with time to start of remdesivir after symptom onset, age, comorbidities, enrollment period, or corticosteroid use. Remdesivir was not associated with any increase in severe or serious adverse events.
The authors concluded that their analysis showed that remdesivir reduced mortality in inpatients with COVID-19 on no or conventional oxygen but was underpowered to evaluate the effects in patients on high-flow or mechanical ventilation. “Our findings are in line with the IDSA [Infectious Diseases Society of America] guidelines and the most recent update of the WHO COVID-19 treatment guidelines, both of which recommend using remdesivir for patients with severe but not critical COVID-19,” they wrote. “To our knowledge, this is the first and only individual patient data meta-analysis on the effects of remdesivir in patients treated in hospital for COVID-19, summarising all existing randomised evidence on the topic including adverse events stratified by organ systems.”
Limitations of the analysis include that all the studies were performed before vaccines were available and before COVID-19 variants including delta and omicron were in circulation, so that the “effect size of remdesivir in patients who have received a complete dose of a COVID-19 vaccine, a booster dose, or who have pre-existing immunity from previous infection remain to be further elucidated,” the authors said.
An accompanying editorial bemoaned how long it took for guidelines to recommend remdesivir for patients like those in the meta-analysis. “In the context of a deadly pandemic, it would have been beneficial for these panels to have erred on the side of inclusiveness and benefit rather than focusing on subgroup and interim results as evidence of no benefit, particularly in light of the robust and positive prespecified overall outcome findings of a placebo-controlled, double-blind, randomised stratified trial with a reassuring patient safety profile (no difference in adverse events between remdesivir and placebo) and the strong biological and clinical plausibility that antiviral benefit would extend to patients in the earlier stages of COVID-19 (before requiring supplemental oxygen),” the editorial said. “How many more lives could have been saved had remdesivir been recommended more broadly and made more readily available?”