Clinical impact of combination therapy with baricitinib, remdesivir, and dexamethasone in patients with severe COVID-19

Izumo, Takehiro; Kuse, Naoyuki; Awano, Nobuyasu; Tone, Mari; Sakamoto, Keita; Takada, Kohei; Muto, Yutaka; Fujimoto, Kazushi; Saiki, Ayae; Ito, Yu; Matsumoto, Haruko; Inomata, Minoru

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide and is also an important disease in Japan. Thus, the optimal treatment strategy for severe COVID-19 should be established urgently. The effects of combination treatment with baricitinib—a Janus kinase inhibitor, remdesivir, and dexamethasone (BRD) are unknown. METHODS: Patients who received combination therapy with BRD at the Japanese Red Cross Medical Center were enrolled in the study. All patients received baricitinib (≤14 d), remdesivir (≤10 d), and dexamethasone (≤10 d). The efficacy and adverse events were evaluated. RESULTS: In total, 44 patients with severe COVID-19 were enrolled in this study. The 28-d mortality rate was low at 2.3 % (1/44 patients). The need for invasive mechanical ventilation was avoided in most patients (90 %, 17/19 patients). Patients who received BRD therapy had a median hospitalization duration of 11 d, time to recovery of 9 d, duration of intensive care unit stay of 6 d, duration of invasive mechanical ventilation of 5 d, and duration of supplemental oxygen therapy of 5 d. Adverse events occurred in 15 patients (34 %). Liver dysfunction, thrombosis, iliopsoas hematoma, renal dysfunction, ventilator-associated pneumonia, infective endocarditis, and herpes zoster occurred in 11 %, 11 %, 2 %, 2 %, 2 %, 2 %, and 2 % of patients, respectively. CONCLUSIONS: Combination therapy with BRD was effective in treating severe COVID-19, and the incidence rate of adverse events was low. The results of the present study are encouraging; however, further randomized clinical studies are needed.