Current best evidence for clinical care (more info)
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-a-2a, 3 million IU each time, twice daily for 10 days), or nebulized IFN-a-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-a-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-a-2a beyond IFN-a-2a alone.
| Discipline / Specialty Area | Score |
|---|---|
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
| Infectious Disease | |
This is a small study population which might lead one to be concerned regarding sufficient power. However, confidence intervals are nearly identical and this might lend some credence to the view that a larger study might have demonstrated similar outcomes. This study does not support any efficacy of Leflunomide in improving post COVID viral shedding.
An early initial report showed possible benefit of the nucleic acid anti-metabolite leflunomide in COVID-19. This randomized trial showed no benefit in hospitalized patients.