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Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study.
PLoS One. 2020; 15(8):e0237693.Plos

Abstract

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.

Authors+Show Affiliations

Division of Outcomes and Value Research, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States of America.Berry Consultants LLC, Austin, Texas, United States of America. M.D. Anderson Cancer Center of the University of Texas, Houston, Texas, United States of America.COTA, Boston, Massachusetts, United States of America.John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States of America.John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States of America.John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States of America.John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States of America.John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States of America.Berry Consultants LLC, Austin, Texas, United States of America.Berry Consultants LLC, Austin, Texas, United States of America.COTA, Boston, Massachusetts, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Hackensack Meridian Health, Hackensack New Jersey and Hackensack Meridian School of Medicine, Nutley, New Jersey, United States of America.Division of Outcomes and Value Research, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States of America.

Pub Type(s)

Journal Article
Multicenter Study
Observational Study

Language

eng

PubMed ID

32790733

Citation

Ip, Andrew, et al. "Hydroxychloroquine and Tocilizumab Therapy in COVID-19 patients-An Observational Study." PloS One, vol. 15, no. 8, 2020, pp. e0237693.
Ip A, Berry DA, Hansen E, et al. Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study. PLoS One. 2020;15(8):e0237693.
Ip, A., Berry, D. A., Hansen, E., Goy, A. H., Pecora, A. L., Sinclaire, B. A., Bednarz, U., Marafelias, M., Berry, S. M., Berry, N. S., Mathura, S., Sawczuk, I. S., Biran, N., Go, R. C., Sperber, S., Piwoz, J. A., Balani, B., Cicogna, C., Sebti, R., ... Goldberg, S. L. (2020). Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study. PloS One, 15(8), e0237693. https://doi.org/10.1371/journal.pone.0237693
Ip A, et al. Hydroxychloroquine and Tocilizumab Therapy in COVID-19 patients-An Observational Study. PLoS One. 2020;15(8):e0237693. PubMed PMID: 32790733.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study. AU - Ip,Andrew, AU - Berry,Donald A, AU - Hansen,Eric, AU - Goy,Andre H, AU - Pecora,Andrew L, AU - Sinclaire,Brittany A, AU - Bednarz,Urszula, AU - Marafelias,Michael, AU - Berry,Scott M, AU - Berry,Nicholas S, AU - Mathura,Shivam, AU - Sawczuk,Ihor S, AU - Biran,Noa, AU - Go,Ronaldo C, AU - Sperber,Steven, AU - Piwoz,Julia A, AU - Balani,Bindu, AU - Cicogna,Cristina, AU - Sebti,Rani, AU - Zuckerman,Jerry, AU - Rose,Keith M, AU - Tank,Lisa, AU - Jacobs,Laurie G, AU - Korcak,Jason, AU - Timmapuri,Sarah L, AU - Underwood,Joseph P, AU - Sugalski,Gregory, AU - Barsky,Carol, AU - Varga,Daniel W, AU - Asif,Arif, AU - Landolfi,Joseph C, AU - Goldberg,Stuart L, Y1 - 2020/08/13/ PY - 2020/05/21/received PY - 2020/08/01/accepted PY - 2020/8/14/entrez PY - 2020/8/14/pubmed PY - 2020/8/29/medline SP - e0237693 EP - e0237693 JF - PloS one JO - PLoS One VL - 15 IS - 8 N2 - Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/32790733/Hydroxychloroquine_and_tocilizumab_therapy_in_COVID_19_patients_An_observational_study_ DB - PRIME DP - Unbound Medicine ER -