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

Curr Med Res Opin. 2021 Jul;37(7):1085-1097. doi: 10.1080/03007995.2021.1920900. Epub 2021 May 19.

Abstract

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 = 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.

Keywords: COVID-19; Favipiravir; discharge; effectiveness; mortality; retrospective; supportive care; trial.

MeSH terms

  • Amides* / adverse effects
  • Amides* / therapeutic use
  • Antiviral Agents* / adverse effects
  • Antiviral Agents* / therapeutic use
  • COVID-19* / epidemiology
  • COVID-19* / therapy
  • Critical Illness / epidemiology
  • Critical Illness / therapy
  • Humans
  • Propensity Score
  • Pyrazines* / adverse effects
  • Pyrazines* / therapeutic use
  • Respiration, Artificial / statistics & numerical data
  • Retrospective Studies
  • SARS-CoV-2
  • Saudi Arabia
  • Sensitivity and Specificity

Substances

  • Amides
  • Antiviral Agents
  • Pyrazines
  • favipiravir