Should Remdesivir Be Used for the Treatment of Patients With COVID-19? Rapid, Living Practice Points From the American College of Physicians (Version 2, Update Alert 3)
Authors: Amir Qaseem, Jennifer Yost, Itziar Etxeandia-Ikobaltzeta, George M. Abraham, Janet A. Jokela, Mary Ann Forciea, Matthew C. Miller, Linda L. Humphrey
Journal: Annals of Internal Medicine (2022)

LettersMay 2022Should Remdesivir Be Used for the Treatment of Patients With COVID-19? Rapid, Living Practice Points From the American College of Physicians (Version 2, Update Alert 3)FREEAmir Qaseem, MD, PhD, MHA, Jennifer Yost, PhD, RN, Itziar Etxeandia-Ikobaltzeta, PharmD, PhD, George M. Abraham, MD, MPH, Janet A. Jokela, MD, MPH, Mary Ann Forciea, MD, Matthew C. Miller, MD, Linda L. Humphrey, MD, MPH, for the Scientific Medical Policy Committee of the American College of Physicians*Amir Qaseem, MD, PhD, MHAAmerican College of Physicians, Philadelphia, Pennsylvania, Jennifer Yost, PhD, RNAmerican College of Physicians, Philadelphia, Pennsylvania, and Villanova University, Villanova, Pennsylvania, Itziar Etxeandia-Ikobaltzeta, PharmD, PhDAmerican College of Physicians, Philadelphia, Pennsylvania, George M. Abraham, MD, MPHUniversity of Massachusetts Medical School and Saint Vincent Hospital, Worcester, Massachusetts, Janet A. Jokela, MD, MPHUniversity of Illinois College of Medicine at Urbana-Champaign, Champaign, Illinois, Mary Ann Forciea, MDPenn Medicine, Philadelphia, Pennsylvania, Matthew C. Miller, MDPenn Medicine, Philadelphia, Pennsylvania, Linda L. Humphrey, MD, MPHPortland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon, for the Scientific Medical Policy Committee of the American College of Physicians*Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-4810 SectionsSupplemental MaterialAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This is an update of the American College of Physicians' living, rapid practice points on the use of remdesivir for treatment of COVID-19 (1–3). This update is based on an updated living, rapid systematic review that included studies published through 19 October 2021 (4) and identified 2 new studies meeting inclusion criteria. One was a primary randomized controlled trial (5); the second was a substudy (6) of a primary randomized controlled trial (7) that was already included in version 2 of the practice points and systematic review (1–3, 8–10) but assesses new data on outcomes of interest not evaluated by the primary study (7). Both new studies evaluated a 10-day course of remdesivir versus standard care. In addition, this update includes data on serious adverse events and any adverse events from 1 substudy (11) not reported in the previous evidence review (10). No new evidence has been identified assessing a 5-day course of remdesivir compared with placebo or standard care or compared with a 10-day course. The Supplement summarizes the key questions and practice point development process and provides an updated evidence overview and summary of findings, clinical considerations, and evidence gaps.Practice PointsThe following practice points are based on the best available evidence about the effectiveness and harms of remdesivir and its variability by symptom duration, disease severity, and treatment duration in patients with COVID-19. The target patient population includes all hospitalized, nonpregnant, adult patients with COVID-19. Although treatment with remdesivir in outpatient settings is an important area of research, these practice points do not address it.Practice Point 1: Consider Remdesivir for 5 Days to Treat Hospitalized Patients With COVID-19 Who Do Not Require Invasive Ventilation or ECMOUpdated RationaleThe evidence update did not result in any changes to our previous overall assessment, as there continues to be an overall net benefit of remdesivir with both a 5-day course (1, 2, 8, 9) and a 10-day course (1, 3, 4, 8, 10) as well as evidence suggesting that 5 days of treatment may be as effective as 10 days (1, 8).None of the new studies evaluated a 5-day course of remdesivir. Assessing the updated evidence evaluating a 10-day course of remdesivir compared with placebo or standard care (4–6, 11), we still judged there to be an overall net benefit (low- to moderate-certainty evidence) for a 10-day course across all outcomes: recovery (modest increase), hospital length of stay (modest reduction), clinical improvement (modest increase), time to recovery (large reduction), time to clinical improvement (slight reduction), need for invasive ventilation or extracorporeal membrane oxygenation (ECMO) at follow-up (slight reduction), and serious adverse events (slight reduction; previously a modest reduction), with no differences in mortality or new need for mechanical ventilation or ECMO and a slight increase in any adverse events (previously little to no difference).The new studies did not evaluate a 5-day course compared with a 10-day course. Thus, our previous conclusion remains unchanged that a 5-day course compared with a 10-day course (1, 8) may reduce mortality (slightly), time to recovery (slightly), and need for invasive ventilation or ECMO at follow-up (slightly) and may increase recovery (modestly) and clinical improvement (modestly) with fewer serious adverse events and fewer of any adverse events (both modestly). In addition, previously reported patient compliance data from 1 study further support clinical advice for considering use of a 5-day course; of patients allocated to receive a 10-day course versus placebo, fewer than half (41.2%) received all 10 doses, with an even lower percentage (38.1%) receiving all 10 doses because they recovered and were discharged from the hospital (12, 13).Previous evidence comparing a 10-day course of remdesivir with placebo or standard care showed a modest reduction in mortality among patients requiring supplemental oxygen (but not invasive ventilation) and little to no difference in mortality in patients not requiring supplemental oxygen at the time a 10-day course was initiated (1, 8). Considering the expectation that most patients with a diagnosis of COVID-19 are admitted with respiratory signs and symptoms, we determined that the evidence is insufficient to advise against considering use of remdesivir in patients who do not require supplemental oxygen at the time of drug initiation.Practice Point 2: Consider Extending the Use of Remdesivir to 10 Days to Treat Hospitalized Patients With COVID-19 Who Develop the Need for Invasive Ventilation or ECMO Within a 5-Day CourseUpdated RationaleOur previous conclusion remains unchanged: Evidence suggests an overall net benefit with a 10-day course of remdesivir (1, 3, 4, 8, 10) and a reduction in mortality with extension of remdesivir treatment to 10 days in hospitalized patients with COVID-19 who progress to requiring ventilation or ECMO by day 5 of remdesivir therapy, both of which outweigh potential harms (8, 14).The updated findings (4–6, 11) show an overall net benefit (low- to moderate-certainty evidence) for a 10-day course across all outcomes: recovery (modest increase), hospital length of stay (modest reduction), clinical improvement (modest increase), time to recovery (large reduction), time to clinical improvement (slight reduction), need for invasive ventilation or ECMO at follow-up (slight reduction), and serious adverse events (slight reduction), with no differences in mortality or new need for invasive ventilation or ECMO and a slight increase in any adverse events. In addition, a previously reported post hoc analysis assessing variation in disease severity (respiratory support requirements) between a 5-day course and a 10-day course suggested that continued treatment through 10 days resulted in lower mortality among patients who progressed to requiring invasive ventilation or ECMO at day 5. However, no improvement was observed in mortality among patients who were receiving noninvasive positive-pressure ventilation, were receiving high- or low-flow oxygen, or were breathing ambient air (8, 14).Practice Point 3: Avoid Initiating Remdesivir to Treat Hospitalized Patients With COVID-19 Who Are Already on Invasive Ventilation or ECMOReaffirmed RationaleThe update did not identify any relevant studies for practice point 3; thus, our previous conclusion remains unchanged. Previous evidence from a pooled subgroup analysis in the systematic review found that patients receiving invasive ventilation or ECMO at the time of drug initiation may have a modest increase in mortality (8), and a post hoc finding in one study showed no improvement in time to recovery among patients receiving invasive ventilation or ECMO at baseline (12, 13) with a 10-day course versus placebo or standard care. These findings are consistent with our current understanding of COVID-19 progression that patients who are admitted on invasive ventilation or ECMO have likely progressed beyond the viral stage of the illness to the inflammatory stage and are less likely to improve with antivirals; hence, it is important to avoid any additional toxicity from remdesivir, in the absence of demonstrated benefit and given possible harms.Retirement From Living StatusThe Scientific Medical Policy Committee has decided to retire this topic from living status in order to balance current priorities with existing resources (15), considering that surveillance was originally planned through December 2021 and the last 3 updates did not result in important changes to conclusions.References1. Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al; Scientific Medical Policy Committee of the American College of Physicians. Should remdesivir be used for the treatment of patients with COVID-19? Rapid, living practice points from the American College of Physicians (Version 2). Ann Intern Med. 2021;174:673-9. [PMID: 33560862] doi:10.7326/M20-8101 LinkGoogle Scholar2. Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al; Scientific Medical Policy Committee of the American College of Physicians. Update alert: should remdesivir be used for the treatment of patients with COVID-19? Rapid, living practice points from the American College of Physicians (Version 2) [Letter]. Ann Intern Med. 2021;174:W66-W67. [PMID: 34251904] doi:10.7326/L21-0389 LinkGoogle Scholar3. Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al; Scientific Medical Policy Committee of the American College of Physicians. Update alert 2: should remdesivir be used for the treatment of patients with COVID-19? Rapid, living practice points from the American College of Physicians (Version 2) [Letter]. Ann Intern Med. 2021;174:W116-W117. [PMID: 34606308] doi:10.7326/L21-0607 LinkGoogle Scholar4. 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. 2022;175:701-9. doi:10.7326/M21-4784 LinkGoogle Scholar5. Abd-Elsalam S, Ahmed OA, Mansour NO, et al. Remdesivir efficacy in COVID-19 treatment: a randomized controlled trial. Am J Trop Med Hyg. 2021. [PMID: 34649223] doi:10.4269/ajtmh.21-0606 CrossrefMedlineGoogle Scholar6. Ader F, Bouscambert-Duchamp M, Hites M, et al; DisCoVeRy Study Group. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial. Lancet Infect Dis. 2022;22:209-21. [PMID: 34534511] doi:10.1016/S1473-3099(21)00485-0 CrossrefMedlineGoogle Scholar7. Pan H, Peto R, Henao-Restrepo AM, et al; WHO Solidarity Trial Consortium. Repurposed antiviral drugs for Covid-19—interim WHO Solidarity Trial results. N Engl J Med. 2021;384:497-511. [PMID: 33264556] doi:10.1056/NEJMoa2023184 CrossrefMedlineGoogle Scholar8. Kaka AS, MacDonald R, Greer N, et al. Major update: remdesivir for adults with COVID-19: a living systematic review and meta-analysis for the American College of Physicians practice points. Ann Intern Med. 2021;174:663-72. [PMID: 33560863] doi:10.7326/M20-8148 LinkGoogle Scholar9. Kaka AS, MacDonald R, Linskens EJ, et al. Update alert: remdesivir for adults with COVID-19 [Letter]. Ann Intern Med. 2021;174:W65. [PMID: 34125578] doi:10.7326/L21-0375 LinkGoogle Scholar10. Kaka AS, MacDonald R, Linskens EJ, et al. Update alert 2: remdesivir for adults with COVID-19 [Letter]. Ann Intern Med. 2021;174:W114-W115. [PMID: 34606312] doi:10.7326/L21-0600 LinkGoogle Scholar11. Barratt-Due A, Olsen IC, Nezvalova-Henriksen K, et al; NOR-Solidarity trial. Evaluation of the effects of remdesivir and hydroxychloroquine on viral clearance in COVID-19: a randomized trial. Ann Intern Med. 2021;174:1261-9. [PMID: 34251903] doi:10.7326/M21-0653 LinkGoogle Scholar12. Beigel JH, Tomashek KM, Dodd LE, et al; ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19—final report. N Engl J Med. 2020;383:1813-26. [PMID: 32445440] doi:10.1056/NEJMoa2007764 CrossrefMedlineGoogle Scholar13. Wilt TJ, Kaka AS, MacDonald R, et al. Remdesivir for adults with COVID-19: a living systematic review for American College of Physicians practice points. Ann Intern Med. 2021;174:209-20. [PMID: 33017170] doi:10.7326/M20-5752 LinkGoogle Scholar14. Goldman JD, Lye DCB, Hui DS, et al; GS-US-540-5773 Investigators. Remdesivir for 5 or 10 days in patients with severe Covid-19. N Engl J Med. 2020;383:1827-37. [PMID: 32459919] doi:10.1056/NEJMoa2015301 CrossrefMedlineGoogle Scholar15. Qaseem A, Yost J, Forciea MA, et al; Scientific Medical Policy Committee of the American College of Physicians. The development of living, rapid practice points: summary of methods from the Scientific Medical Policy Committee of the American College of Physicians. Ann Intern Med. 2021;174:1126-32. [PMID: 34029483] doi:10.7326/M20-7641 LinkGoogle Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: American College of Physicians, Philadelphia, PennsylvaniaAmerican College of Physicians, Philadelphia, Pennsylvania, and Villanova University, Villanova, PennsylvaniaUniversity of Massachusetts Medical School and Saint Vincent Hospital, Worcester, MassachusettsUniversity of Illinois College of Medicine at Urbana-Champaign, Champaign, IllinoisPenn Medicine, Philadelphia, PennsylvaniaPortland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon* This article, written by Amir Qaseem, MD, PhD, MHA; Jennifer Yost, RN, PhD; Itziar Etxeandia-Ikobaltzeta, PharmD, PhD; George M. Abraham, MD, MPH; Janet A. Jokela, MD, MPH; Mary Ann Forciea, MD; Matthew C. Miller, MD; and Linda L. Humphrey, MD, MPH, was developed for the Scientific Medical Policy Committee of the American College of Physicians. Individuals who served on the Scientific Medical Policy Committee from initiation of the project until its approval were Linda L. Humphrey, MD, MPH† (Chair); Adam J. Obley, MD‡ (Vice Chair); Andrew Dunn, MD, MPH‡; Robert M. Centor, MD‡ (Immediate Past Vice Chair); Elie A. Akl, MD, MPH, PhD‡; Rebecca Andrews, MS, MD†; Thomas A. Bledsoe, MD‡; Mary Ann Forciea, MD†; Ray Haeme§†; Janet A. Jokela, MD, MPH†; Devan L. Kansagara, MD, MCR‡; Maura Marcucci, MD, MSc‡; Matthew C. Miller, MD†; and CDR Mark P. Tschanz, DO†. Kate Carroll, MPH, and Shannon Merillat, MPH, MLIS, were nonauthor contributors from ACP staff. Approved by the ACP Executive Committee of the Board of Regents on behalf of the Board of Regents on 7 February 2022.† Author.‡ Nonauthor contributor.§ Nonphysician public representative.Note: The practice points are meant to guide care based on the best available evidence and may not apply to all patients or individual clinical situations. They should not be used as a replacement for a clinician's judgment. Any reference to a product or process contained in a practice point is not intended as an endorsement of any specific commercial product. All practice points are considered automatically withdrawn or invalid 5 years after publication or once an update has been issued.Financial Support: Financial support for the development of the Practice Points comes exclusively from the ACP operating budget.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-4810. All financial and intellectual disclosures of interest were declared, and potential conflicts were discussed and managed. Dr. Obley participated in discussion of the practice points but was recused from authorship and voting due to a moderate-level conflict of interest (author of supporting systematic review). Drs. Dunn, Kansagara, and Marcucci participated in discussion but were recused from authorship and voting due to moderate-level conflicts of interest (authors of recent relevant systematic reviews). A record of disclosures of interest and management of conflicts is kept for each Scientific Medical Policy Committee meeting and conference call and can be viewed at www.acponline.org/about-acp/who-we-are/leadership/boards-committees-councils/scientific-medical-policy-committee/disclosure-of-interests-and-conflict-of-interest-management-summary-for-scientific-medical-policy.Corresponding Author: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, [email protected]org.This article was published at Annals.org on 1 March 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMajor Update 2: Remdesivir for Adults With COVID-19: A Living Systematic Review and Meta-analysis for the American College of Physicians Practice Points Anjum S. Kaka , Roderick MacDonald , Eric J. Linskens , Lisa Langsetmo , Kathryn Vela , Wei Duan-Porter , and Timothy J. Wilt Metrics May 2022Volume 175, Issue 5Page: W55-W57KeywordsCOVID-19Drug therapyInpatientsSystematic reviews ePublished: 1 March 2022 Issue Published: May 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...