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 twice daily loading dose, followed by 800 mg or 600 mg twice daily) 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 ¼ 9-10) in the favipiravir arm versus 15 days (95%CI ¼ 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 ¼ 1.56-2.46). Progression to mechanical ventilation was slower with favipiravir (HR adj ¼ 0.10, 95%CI ¼ 0.04-0.29). There was no significant effect on mortality (HR adj ¼ 1.56, 95%CI ¼ 0.73-3.36). There was a statistically non-significant trend toward worse outcomes in the critical category (HR adj ¼ 2.80, 95%CI ¼ 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.