Effectiveness of Remdesivir Treatment Protocols Among Patients Hospitalized with COVID-19: A Target Trial Emulation.

Background: Remdesivir is recommended for certain hospitalized patients with COVID-19. However, these recommendations are based on evidence from small randomized trials, early observational studies, or expert opinion. Further investigation is needed to better inform treatment guidelines with regard to the effectiveness of remdesivir among these patients.
Methods: We emulated a randomized target trial using chargemaster data from 333 US hospitals from 1 May 2020 to 31 December 2021. We compared three treatment protocols: remdesivir within 2 days of hospital admission, no remdesivir within the first 2 days of admission, and no remdesivir ever. We used baseline comorbidities recorded from encounters up to 12 months before admission and identified the use of in-hospital medications, procedures, and oxygen supplementation from charges. We estimated the cumulative incidence of mortality or mechanical ventilation/extracorporeal membrane oxygenation with an inverse probability of censoring weighted estimator. We conducted analyses in the total population as well as in subgroups stratified by level of oxygen supplementation.
Results: A total of 274,319 adult patients met the eligibility criteria for the study. Thirty-day in-hospital mortality risk differences for patients adhering to the early remdesivir protocol were -3.1% (95% confidence interval = -3.5%, -2.7%) compared to no early remdesivir and -3.7% (95% confidence interval -4.2%, -3.2%) compared to never remdesivir, with the strongest effect in patients needing high-flow oxygen. For mechanical ventilation/extracorporeal membrane oxygenation, risk differences were minimal.
Conclusions: We estimate that, among hospitalized patients with COVID-19, remdesivir treatment within 2 days of admission reduced 30-day in-hospital mortality, particularly for patients receiving supplemental oxygen on the day of admission.
Competing Interests: A.B. is an employee of and owns equity in Regeneron Pharmaceuticals. At the time of writing, he was an employee of NoviSci/Target RWE. C.W. is an employee of and owns equity in NoviSci/Target RWE. A.A. has received consulting fees from Merck and Gilead; her institution has received funding from Merck and Gilead for her research. R.S.B. receives research and consulting grants from Gilead, as well as institutional grants from TARGET-HCC, TARGET-NASH, and HCV-TARGET. C.L. receives research funding from Gilead, Pfizer, and Lilly. K.R.R. serves as an advisor to Spark Therapeutics, Mallinckrodt, Novo Nordisk, and Genfit; he receives research support (paid to the University of Pennsylvania) from Gilead, Merck, BMS, Intercept, Exact Sciences, Biovie, Sequana, Grifols, TARGET-HCC, HCV-TARGET, and TARGET-NASH; he serves on a DSMB for Novartis. E.C.V. declares no conflicts of interest. J.M.C. is an employee of and owns equity in Target RWE. A.M. is an employee of and owns equity in Target RWE. M.W.F. is Chief Medical Officer for TARGET RWE and receives personal fees and is a stockholder in the company. M.A.B. serves on scientific advisory committees for AbbVie, Amgen, Astellas/Seagan, Atara Biotherapeutics, Brigham and Women’s Hospital, Kite/Gilead, and Vertex; he receives consulting fees and owns equity in NoviSci/Target RWE.
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