Systematic Review Provides Updated Guidance for Use of Remdesivir among Individuals with COVID-19
BACKGROUND:
The FDA recently approved remdesivir for patients with COVID-19 who are older than 12 years and are hospitalized in a facility that can provide care similar to an acute care hospital. However, recommendations on the use of remdesivir for COVID-19 can vary. For example, while the World Health Organization (WHO) conditionally recommends against its use, the National Institutes of Health and Infectious Diseases Society of America continue to recommend remdesivir on the basis of disease severity. Thus, investigators updated their previous systematic review of remdesivir for adults with COVID-19 to include new meta-analyses of patients with COVID-19 – of any severity – compared with a control. From 193 full-text article reviews, this update includes five randomized controlled trials (RCTs), which enrolled 7,767 patients worldwide, and incorporated data from a new large RCT, as well as final results of a previous RCT. All trials reviewed remdesivir that was administered intravenously. The primary outcome in four RCTs was time to clinical improvement or symptom recovery, and in one RCT it was in-hospital all-cause mortality through 28 days.
FINDINGS:
- Compared with controls, a 10-day course of remdesivir probably results in little to no mortality reduction but may result in a small reduction in the proportion receiving mechanical ventilation.
- Compared with a 10-day course of remdesivir for patients not requiring ventilation at baseline, a 5-day course may reduce mortality, the need for ventilation, and serious adverse events while increasing the percentage of patients who recovered or clinically improved.
- Effect on hospital length of stay or the percentage of those remaining hospitalized is mixed.
- Among patients already receiving invasive mechanical ventilation remdesivir may not reduce time to recovery and may increase mortality.
- Serious adverse events reported in trials include a combination of clinical findings resulting from COVID-19 progression (e.g., respiratory failure) and direct remdesivir toxicity.
IMPLICATIONS:
- For patients not receiving ventilation, a 5-day course of remdesivir may provide greater benefits and fewer harms with lower drug costs than a 10-day course. The American College of Physicians’ Scientific Medical Policy Committee used this updated systematic review to develop a new Practice Points document to guide clinicians on the use of remdesivir.
LIMITATIONS:
- Summarizing findings was challenging due to varying disease severity definitions and outcomes.
AUTHOR/FUNDING INFORMATION:
This rapid review was funded by HSR&D’s Evidence Synthesis Program. Drs. Duan-Porter and Wilt are core investigators with HSR&D’s Center for Care Delivery and Outcomes Research (CCDOR). Mr. MacDonald and Drs. Greer, Duan-Porter, and Wilt are part of the Minneapolis VA Health Care System, and Dr. Obley is part of the VA Portland Health Care System.
Kaka A, MacDonald R, Greer N, Vela K, Duan-Porter W, Obley A, and Wilt T. A Living Systematic Review and Meta-Analysis for the American College of Physician Practice Points. Annals of Internal Medicine. February 9, 2021. Online ahead of print.
