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

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.

Figure 1.. Description of Patients Included in the Analysis

JHHS indicates the Johns Hopkins Health System.

Figure 2.. Time to Clinical Improvement

Cumulative incidence curves for time to clinical improvement are shown for the entire remdesivir and matched control cohort (A); patients with severe disease (requiring high-flow nasal cannula, noninvasive ventilation, mechanical ventilation, extracorporeal membrane oxygenation, or vasopressors) (B); patients with mild to moderate disease (on ambient air or nasal cannula oxygen) (C); and patients who would have met Adaptive COVID-19 Treatment Trial 1 (ACTT-1) study criteria (D). aHR indicates adjusted hazard ratio.

Figure 3.. Patient Survival

Kaplan-Meier survival curves are shown for the entire remdesivir and matched control cohort (A); patients with severe disease (requiring high-flow nasal cannula, noninvasive ventilation, mechanical ventilation, extracorporeal membrane oxygenation, or vasopressors) (B); patients with mild to moderate disease (on ambient air or nasal cannula oxygen) (C); and patients who would have met Adaptive COVID-19 Treatment Trial 1 (ACTT-1) study criteria (D). aHR indicates adjusted hazard ratio.

Figure 4.. Clinical Improvement, Mortality, and Survival Rates by Receipt of Remdesivir Alone or Plus Corticosteroids

A, Time to clinical improvement for patients who received remdesivir, excluding patients who also received corticosteroids. B, Adjusted cumulative improvement curve for patients who received remdesivir plus corticosteroids vs those who received remdesivir alone, adjusted using marginal structural Cox models. C, Kaplan-Meier survival curves for patients who received remdesivir, excluding patients who also received corticosteroids. D, Adjusted survival curve for patients who received remdesivir plus corticosteroids vs those who received remdesivir alone, adjusted using marginal structural Cox proportional hazards regression models. aHR indicates adjusted hazard ratio.