The American College of Physicians (ACP) has released the final update to their rapid, living practice points on the use of remdesivir in adults hospitalized with COVID-19 infection. The summary of the guidance was published in the Annals of Internal Medicine.
Remdesivir is a nucleotide analogue prodrug that inhibits viral RNA. Remdesivir was approved by the US Food and Drug Administration (FDA) for the treatment of COVID-19 infection. The Practice Points’ researchers previously concluded that a 10-day course of remdesivir had an insignificant effect on mortality but most likely decreased the risk for severe adverse events and the time to recovery.
Following the most recent update on the use of remdesivir for the treatment of COVID-19 in August 2021, results from 1 new randomized clinical trial and 1 subtrial were published. A systematic review and meta-analysis was conducted for this update using all available data from 5 randomized clinical trials and 2 subtrials, both of which assessed the effect of remdesivir in adult patients hospitalized with COVID-19 infection.
Compared with standard care, the meta-analysis showed that treatment with a 5- or 10-day course of remdesivir had outcomes similar to those published in the previous guidance on remdesivir.
In regard to the outcomes of remdesivir treatment, a random-effects model showed that adult patients hospitalized with COVID-19 infection who received a 10-day course of remdesivir had a similar risk of all-cause mortality (risk ratio [RR], 0.94; 95% CI, 0.79-1.12; I2 =0%) compared with those who received placebo.
A fixed-effects model showed that the risk of all nonmortality outcomes was decreased in patients who received remdesivir vs those who received placebo (RR, 1.10; 95% CI, 1.04-1.15; I2=0%). Compared with placebo, treatment with remdesivir was also found to decrease the risk for requiring either invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) at follow-up on days 11, 14, and 15 (RR, 0.74; 95% CI, 0.62-0.89; I2=13%). However, the risk for IMV or ECMO was not significantly different in patients who received remdesivir vs those who received placebo at day 28 and at 6 months (RR, 0.87; 95% CI, 0.64-1.18; I2=50%).
Owing to the lack of new findings in these updated practice points, the researchers reaffirmed the recommendation for patients who do not require IMV or ECMO to receive treatment with a 5- rather than a 10-day course of remdesivir. The previous guidance on remdesivir for COVID-19 infection determined that a 5-day course was associated with moderate clinical improvement. In addition, a 5-day course of remdesevir also was associated with a decrease in the rate of adverse events, as well as a mild decrease in the risk of all-cause mortality, time to recovery, and need for IMV or ECMO.
For patients with COVID-19 infection who receive a 5-day course of remdesivir and subsequently require IMV or ECMO, treatment with remdesivir should be extended to a 10-day course. Results of a post hoc analysis found that patients who were switched from a 5- to a 10-day course of remdesivir had moderate clinical improvement, a decreased risk of mortality and need for IMV or ECMO, and a significant decrease in the time to recovery.
Remdesivir should not be initiated in patients currently receiving IMV or ECMO. Previous evidence indicated that patients who were receiving ventilation support at the time of remdesivir initiation were at increased risk of all-cause mortality, with no improvement in the time to recovery. The researchers suggested that patients with COVID-19 infection who require IMV or ECMO have likely progressed to the inflammatory rather than the viral phase of disease, making antiviral medications ineffective and more likely to increase the risk for adverse events due to toxicity.
The scientific medical policy committee of the ACP has retired the living status of this guidance because the previous 3 updates found no evidence to support alternative guidance in regard to the use of remdesivir for COVID-19 infection.
Although this is the final update on the use of remdesivir in adults with COVID-19 infection, the researchers noted “ongoing trials of remdesivir for COVID-19 evaluating formulations and [patient] populations not previously studied, which may alter [clinical] practice and policy.”
Disclosure: An author declared affiliations with industry. Please see the original reference for a full list of disclosures.
Kaka AS, MacDonald R, Linskens EJ, et al. Major update 2: remdesivir for adults with COVID-19: a living systematic review and meta-analysis for the American College of Physicians practice points. Ann Intern Med. Published online March 1, 2022. doi:10.7326/M21-4784