Abstract
Background: We aimed to evaluate the efficacy and safety of leflunomide, an approved dihydroorotate dehydrogenase inhibitor, to treat coronavirus disease 2019 (COVID-19) patients with prolonged postsymptomatic viral shedding.
Methods: We conducted a prospective, randomized controlled, open-label trial involving hospitalized adult COVID-19 patients with prolonged polymerase chain reaction (PCR) positivity. Patients were randomly assigned to receive either leflunomide (50 mg every 12 hours, 3 consecutive times, orally; then 20 mg once daily for 8 days), in addition to nebulized interferon alpha 2a (IFN-α-2a, 3 million IU each time, twice daily for 10 days), or nebulized IFN-α-2a alone for 10 days. The primary endpoint was the duration of viral shedding.
Results: A total of 50 COVID-19 patients with prolonged PCR positivity were randomized into 2 groups: 26 were assigned to the leflunomide plus IFN-α-2a group, and 24 were assigned to the interferon-alone group. Treatment with leflunomide was not associated with a difference from the interferon-alone group in the duration of viral shedding (hazard ratio for negative reverse-transcription PCR, 0.70 [95% confidence interval, .391-1.256]; P = .186). In addition, the patients given leflunomide did not have a substantially shorter length of hospital stay than patients treated with interferon alone, with median durations of 29.0 (interquartile range [IQR], 19.3-47.3) days and 33.0 (IQR, 29.3-42.8) days, respectively (P = .170). Two leflunomide recipients were unable to complete the full 10-day course of administration due to adverse events.
Conclusions: In COVID-19 patients with prolonged PCR positivity, no benefit in terms of the duration of viral shedding was observed with the combined treatment of leflunomide and IFN-α-2a beyond IFN-α-2a alone.
Keywords: COVID-19; SARS-CoV-2; interferon alpha 2a; leflunomide; viral shedding.
【저자키워드】 COVID-19, SARS-CoV-2, viral shedding, interferon alpha 2a, leflunomide, 【초록키워드】 coronavirus disease, Coronavirus disease 2019, Hospitalized, Trial, Open-label, interferon, viral shedding, adverse events, Randomized, polymerase chain reaction, PCR, Patient, Efficacy and safety, Interferon alpha, inhibitor, PCR positivity, leflunomide, administration, primary endpoint, COVID-19 patient, Hospital stay, Chain Reaction, open-label trial, once daily, confidence interval, interquartile range, hazard ratio, treat, nebulized, recipient, combined treatment, Complete, benefit, Randomly, polymerase chain, Course, evaluate, the patient, addition, approved, conducted, median, assigned, receive, adult COVID-19 patient, IQR, patients treated, 【제목키워드】 clinical, shedding, Prolonged, Controlled,