Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19
Authors: Bruno Luís de Castro Araujo
Journal: Annals of Internal Medicine (2021)

LettersMarch 2021Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19FREEBruno Luís de Castro Araujo, MD, MScBruno Luís de Castro Araujo, MD, MScSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-1425 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: We read Skipper and colleagues' article (1) about the use of HCQ for the treatment of outpatients with early coronavirus disease 2019 (COVID-19)–compatible symptoms or a confirmed diagnosis of COVID-19 with interest. Despite the absence of a statistically significant difference in any of the selected outcomes, the negative results of this study must be interpreted with caution. At first, the authors established as a primary outcome an ordinal scale of disease severity (not hospitalized, hospitalized, intensive care unit stay, or death). The evaluation was influenced by the lower-than-expected incidence of hospitalizations that after interim analysis required the primary outcome to change. Another relevant issue is that the study was originally scaled to find a 50% reduction in those outcomes, which seems overly optimistic.The HCQ group surprisingly had a 50% lower incidence of a composite outcome for hospitalization and death for any cause (reported P = 0.29). Patients treated with HCQ made up 24% of those with persistent COVID-19–compatible symptoms at 14 days versus 30% of the placebo group, denoting a nonsignificant absolute reduction of 20% between groups (P = 0.21). If confirmed in adequately dimensioned trials, this difference is clinically meaningful. The new primary outcome (that is, mean reduction from baseline in a 10-point visual analogue scale for disease severity) at day 14 was close to 1.0 point in the placebo group, indicating lack of relevance of that end point in practice at the time of follow-up. Nevertheless, at 10 days of randomization (11 to 14 days after the start of symptoms), there was a 0.42-point absolute reduction in the visual analogue scale (P = 0.050).Use of HCQ in patients with COVID-19 has a low a priori belief of clinical benefit because of unavailable translational evidence, lack of benefit in previous research with other viruses, and no benefit in previous adequately performed observational research and randomized controlled trials (2, 3). The absolute results reported must be considered with caution and interpreted within the limits of the CI for all outcomes. The results of Skipper and colleagues' study naturally do not support the use of HCQ in early COVID-19. However, their findings offer insight for future research in such specific populations and do not prove a lack of any clinically relevant benefit.References1. Skipper CP, Pastick KA, Engen NW, et al. Hydroxychloroquine in nonhospitalized adults with early COVID-19. A randomized trial. Ann Intern Med. 2020;173:623-31. doi:10.7326/M20-4207 LinkGoogle Scholar2. Schluger NW. The saga of hydroxychloroquine and COVID-19: a cautionary tale [Editorial]. Ann Intern Med. 2020;173:662-3. doi:10.7326/M20-5041 LinkGoogle Scholar3. Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19. N Engl J Med. 2020;383:517-25. [PMID: 32492293] doi:10.1056/NEJMoa2016638 CrossrefMedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Bruno Luís de Castro Araujo, MD, MScDisclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L20-1425. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHydroxychloroquine in Nonhospitalized Adults With Early COVID-19 Caleb P. Skipper , Katelyn A. Pastick , Nicole W. Engen , Ananta S. Bangdiwala , Mahsa Abassi , Sarah M. Lofgren , Darlisha A. Williams , Elizabeth C. Okafor , Matthew F. Pullen , Melanie R. Nicol , Alanna A. Nascene , Kathy H. Hullsiek , Matthew P. Cheng , Darlette Luke , Sylvain A. Lother , Lauren J. MacKenzie , Glen Drobot , Lauren E. Kelly , Ilan S. Schwartz , Ryan Zarychanski , Emily G. McDonald , Todd C. Lee , Radha Rajasingham , and David R. Boulware Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 Caleb P. Skipper , David R. Boulware Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 Anusuya Bhattacharyya , Phulen Sarma , Hardeep Kaur , Bikash Medhi Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 Claudia N. Paiva , Daniel V. Tausk Metrics March 2021Volume 174, Issue 3Page: 433-434 ePublished: 16 March 2021 Issue Published: March 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...