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Comparison of Time to Clinical Improvement With vs Without Remdesivir Treatment in Hospitalized Patients With COVID-19

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Does time to clinical improvement or time to death differ among hospitalized patients treated with vs without remdesivir (alone or with corticosteroids) for coronavirus disease 2019 outside of a clinical trial?

Findings  In this multicenter comparative effectiveness research study that included 2483 consecutive admissions with a high proportion of non-White individuals, treatment with remdesivir was associated with more rapid clinical improvement than no remdesivir receipt in propensity score–matched controls. The addition of corticosteroids to remdesivir was not associated with improved time to death.

Meaning  Remdesivir administration is associated with more rapid clinical improvement than no remdesivir receipt among patients with coronavirus disease 2019.

Abstract

Importance  Clinical effectiveness data on remdesivir are urgently needed, especially among diverse populations and in combination with other therapies.

Objective  To examine whether remdesivir administered with or without corticosteroids for treatment of coronavirus disease 2019 (COVID-19) is associated with more rapid clinical improvement in a racially/ethnically diverse population.

Design, Setting, and Participants  This retrospective comparative effectiveness research study was conducted from March 4 to August 29, 2020, in a 5-hospital health system in the Baltimore, Maryland, and Washington, DC, area. Of 2483 individuals with confirmed severe acute respiratory syndrome coronavirus 2 infection assessed by polymerase chain reaction, those who received remdesivir were matched to infected individuals who did not receive remdesivir using time-invariant covariates (age, sex, race/ethnicity, Charlson Comorbidity Index, body mass index, and do-not-resuscitate or do-not-intubate orders) and time-dependent covariates (ratio of peripheral blood oxygen saturation to fraction of inspired oxygen, blood pressure, pulse, temperature, respiratory rate, C-reactive protein level, complete white blood cell count, lymphocyte count, albumin level, alanine aminotransferase level, glomerular filtration rate, dimerized plasmin fragment D [D-dimer] level, and oxygen device). An individual in the remdesivir group with k days of treatment was matched to a control patient who stayed in the hospital at least k days (5 days maximum) beyond the matching day.

Exposures  Remdesivir treatment with or without corticosteroid administration.

Main Outcomes and Measures  The primary outcome was rate of clinical improvement (hospital discharge or decrease of 2 points on the World Health Organization severity score), and the secondary outcome, mortality at 28 days. An additional outcome was clinical improvement and time to death associated with combined remdesivir and corticosteroid treatment.

Results  Of 2483 consecutive admissions, 342 individuals received remdesivir, 184 of whom also received corticosteroids and 158 of whom received remdesivir alone. For these 342 patients, the median age was 60 years (interquartile range, 46-69 years), 189 (55.3%) were men, and 276 (80.7%) self-identified as non-White race/ethnicity. Remdesivir recipients had a shorter time to clinical improvement than matched controls without remdesivir treatment (median, 5.0 days [interquartile range, 4.0-8.0 days] vs 7.0 days [interquartile range, 4.0-10.0 days]; adjusted hazard ratio, 1.47 [95% CI, 1.22-1.79]). Remdesivir recipients had a 28-day mortality rate of 7.7% (22 deaths) compared with 14.0% (40 deaths) among matched controls, but this difference was not statistically significant in the time-to-death analysis (adjusted hazard ratio, 0.70; 95% CI, 0.38-1.28). The addition of corticosteroids to remdesivir was not associated with a reduced hazard of death at 28 days (adjusted hazard ratio, 1.94; 95% CI, 0.67-5.57).

Conclusions and Relevance  In this comparative effectiveness research study of adults hospitalized with COVID-19, receipt of remdesivir was associated with faster clinical improvement in a cohort of predominantly non-White patients. Remdesivir plus corticosteroid administration did not reduce the time to death compared with remdesivir administered alone.

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Article Information

Accepted for Publication: February 4, 2021.

Published: March 24, 2021. doi:10.1001/jamanetworkopen.2021.3071

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Garibaldi BT et al. JAMA Network Open.

Corresponding Author: Brian T. Garibaldi, MD, MEHP, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 1830 E Monument St, Fifth Floor, Baltimore, MD 21205 (Bgariba1@jhmi.edu).

Author Contributions: Dr Garibaldi and Mr. K. Wang contributed equally to this article and are considered co–first authors. Dr Garibaldi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Garibaldi, K. Wang, Robinson, Zeger, Bandeen-Roche, Gupta, Bollinger, Xu.

Acquisition, analysis, or interpretation of data: Garibaldi, K. Wang, Robinson, Zeger, M.-C. Wang, Alexander, Gupta, Bollinger, Xu.

Drafting of the manuscript: Garibaldi, K. Wang, Xu.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Garibaldi, K. Wang, Robinson, Zeger, Bandeen-Roche, M.-C. Wang, Xu.

Obtained funding: Garibaldi.

Administrative, technical, or material support: Garibaldi, Robinson, Gupta, Bollinger.

Supervision: Garibaldi.

Conflict of Interest Disclosures: Dr Garibaldi reported receiving personal fees from Janssen Research and Development LLC and from the US Food and Drug Administration (FDA) Pulmonary-Asthma Drug Advisory Committee outside the submitted work. Dr Bandeen-Roche reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Alexander reported being a past Chair of the US FDA Peripheral and Central Nervous System Advisory Committee; being a co-founding principal and equity holder in Monument Analytics; and receiving personal fees from IQVIA and OptumRx. Dr Gupta reported receiving grants from the NIH outside the submitted work. No other disclosures were reported.

Funding/Support: This work was supported by funding from John Hopkins inHealth, the Johns Hopkins Precision Medicine initiative through JH-CROWN, and the coronavirus disease 2019 (COVID-19) Administrative Supplement for the US Departmentof Health and Human Services (HHS) Region 3 Treatment Center from the Office of the Assistant Secretary for Preparedness and Response (to Drs Garibaldi, Robinson, Gupta, and Xu and Mr K. Wang).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: The authors thank the Johns Hopkins Health System and its surrounding communities for working together to provide outstanding patient care and to keep one another safe during these extraordinary times.

Additional Information: The data used for this publication were part of JH-CROWN: The COVID Precision Medicine Analytics Platform (PMAP) Registry, which is based on contributions from many patients and clinicians.

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