Safety and Efficacy of Combination Therapy of Remdesivir, Baricitinib, and High-dose Steroids in Patients Hospitalized with Moderate to Severe COVID-19

Objective Dexamethasone, remdesivir (REM), and baricitinib (BAR) are commonly used to treat coronavi-rus disease 2019 (COVID-19). High-dose steroids have also been reported to be well tolerated, even when used in combination with multiple drugs. In this retrospective study, we assessed the safety and therapeutic efficacy of a three-drug combination of high-dose steroids, REM, and BAR in hospitalized COVID-19 pa-tients.Methods We retrospectively evaluated the safety and efficacy of three-drug combination therapy.Patients We evaluated 107 patients hospitalized with moderate or severe COVID-19 who underwent 3-drug combination therapy with high-dose steroids (80 mg of methylprednisolone or more, REM, and BAR) in our institution from December 2020 to June 2021. The mean age was 62.1 +/- 13.7 years old, and 71.2% were men. The severity of the study patients was as follows: 18 (16.8%) with an 8-category ordinal score of 4, 84 (78.5%) with a score of 5, and 5 (4.7%) with a score of 6. Results The frequency of high-grade adverse events was low, except for hyperglycemia (n=59, 45.8%). The median duration from symptom onset to the start of three-drug combination therapy was eight days. All but one of the patients treated with the combination therapy improved. The median time to improvement by 1 category of the eight-category ordinal score was 6 days, and the 28-day mortality was 0.9%.Conclusion This study showed the safety profile of three-drug combination therapy of high-dose steroids, REM, and BAR in moderate to severe COVID-19 patients. The three-drug combination therapy is well toler-ated and has the potential to prevent exacerbation of severity.