Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients – An Observational Study (original) (raw)

, View ORCID ProfileDonald A. Berry, Eric Hansen, View ORCID ProfileAndre H. Goy, Andrew L Pecora, Brittany A Sinclaire, Urszula Bednarz, Michael Marafelias, Scott M. Berry, Nicholas S. Berry, Shivam Mathura, Ihor S Sawczuk, Noa Biran, View ORCID ProfileRonaldo C Go, Steven Sperber, Julia A Piwoz, Bindu Balani, Cristina Cicogna, Rani Sebti, Jerry Zuckerman, Keith M Rose, Lisa Tank, Laurie G Jacobs, Jason Korcak, Sarah L. Timmapuri, Joseph P. Underwood, Gregory Sugalski, Carol Barsky, Daniel W. Varga, Arif Asif, Joseph C Landolfi, View ORCID ProfileStuart L Goldberg

doi: https://doi.org/10.1101/2020.05.21.20109207

Abstract

Background Hydroxychloroquine has been touted as a COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has been proposed as a treatment of critically ill patients.

Objective To describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients.

Design Retrospective observational cohort study of electronic health records Setting: 13-hospital network spanning the state of New Jersey.

Participants Patients hospitalized 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.

Main Outcomes The primary outcome was death.

Results 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%.

Conclusions 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

Competing Interest Statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi\_disclosure.pdf and declare: no support from any organisation for the submitted work; AHG reports consulting for Physician Education Resource, LLC on COVID for Oncologists; no other relationships or activities that could appear to have influenced the submitted work.

Clinical Trial

NCT04347993

Funding Statement

No external funding was received for this submission.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Hackensack Meridian Health IRB gave expedited review and approval of our study. Waiver of informed consent and HIPAA authorization was obtained as this was a non-interventional study of routinely collected data for secondary research purposes.

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

Yes

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Data Availability

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