Real-World Safety and Effectiveness of Remdesivir and Corticosteroids in Hospitalized Patients with COVID-19

ABSTRACT

Real-world effectiveness studies of remdesivir in hospitalized patients with COVID-19 conducted to date have produced conflicting findings which may be due, in part, to treatment heterogeneity within standard of care comparison groups. Our objective was to evaluate the comparative effectiveness and safety of remdesivir in a cohort of patients all treated with corticosteroids. We conducted a retrospective cohort study in the National Veterans Affairs Healthcare System. We included hospitalized patients (>18 years old) with positive COVID-19 PCR tests and COVID-19 diagnosis codes, and corticosteroid treatment within 2 days of admission, from 1 May 2020 to 30 November 2021. Time-to-event outcomes included time to inpatient mortality (primary), discharge, mortality after discharge, readmission, and acute kidney injury and bacterial infection after treatment initiation. Propensity score (PS)-adjusted, PS-matched, and inverse probability of treatment weighted (IPTW) Cox proportional hazards regression models controlled for study timeframe, supplemental oxygen, vaccination status, and other important confounders. We observed significantly lower inpatient mortality, 90-day post-discharge mortality, 30-day post-discharge readmission, and significantly longer hospital stays in the remdesivir group (n = 14,509) compared with the non-remdesivir group (n = 4365). Higher rates of bacterial infections were observed in the remdesivir group. Acute kidney injury was lower in subgroup analyses restricting the study population to index dates in 2021, on supplemental oxygen, and fully vaccinated, and higher in those without baseline supplemental oxygen. When comparing the effectiveness and safety of remdesivir plus corticosteroids to a homogenous comparison group, all also treated with corticosteroids, mortality and readmission were significantly lower in the remdesivir group. Longer length of stay corresponds with duration of remdesivir treatment and may impact the risk of developing infections during the hospitalization, which requires further study.