Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: A retrospective study with propensity score matching sensitivity analysis.

INTRODUCTION Favipiravir is a repurposed drug to treat coronavirus 2019 (COVID-19). Due to a lack of available real-world data, we assessed its effectiveness and safety in moderately to critically ill COVID-19 patients. METHODS This retrospective study was conducted in two public/specialty hospitals in Saudi Arabia. We included patients (≥ 18 years) admitted April-August 2020 with confirmed SARS-CoV-2 diagnosed by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab. Patients received either favipiravir (1800 mg or 1600 mg BID loading dose, followed by 800 mg or 600 mg QD) or supportive-care treatment. Patients were excluded if they were outside the study period, classified as having a mild form of the disease per WHO criteria, or had an incomplete patient file. Kaplan-Meier (KM) models were used to estimate median time to discharge. Discharge ratios, progression to mechanical ventilation, and mortality outcomes were estimated across the severity spectrum using Cox proportional-hazards models. As a sensitivity analysis, we performed propensity score-matching (PSM) analysis. RESULTS Overall, median time to discharge was 10 days (95%CI =9-10) in the favipiravir arm versus 15 days (95%CI =14-16) in the supportive-care arm. The accelerated discharge benefit was seen across the COVID-19 spectrum of severity. The adjusted discharge ratio was 1.96 (95%CI =1.56-2.46). Progression to mechanical ventilation was slower with favipiravir (HRadj=0.10, 95%CI =0.04-0.29). There was no significant effect on mortality (HRadj=1.56, 95%CI =0.73-3.36). There was a statistically non-significant trend toward worse outcomes in the critical category (HRadj=2.80, 95%CI =0.99-7.89). Age was an independent risk factor for mortality in mechanically ventilated patients. PSM analyses confirmed these findings. CONCLUSION Favipiravir was associated with clinical benefits, including accelerated discharge rate and less progression to mechanical ventilation; however, no overall mortality benefits were seen across the severity spectrum.