Clinical usefulness of favipiravir in moderate COVID-19 patients: Indian real-world experience

ABSTRACT

Introduction: Favipiravir, a broad-spectrum antiviral agent, acts by inhibiting RNA-dependent RNA polymerase. It is approved in India in the management of mild-moderate COVID-19. It has shown potent in vitro activity against SARS-CoV-2. It has a wide therapeutic safety margin indicated by a wide CC50/EC50 ratio for a high dose. It has shown promising results in clinical studies conducted in China, Russia, Japan, and India. Treatment guidelines from many countries and some states from India have included favipiravir in the treatment protocol. A recently published phase III trial on favipiravir in India has shown early clinical resolution and acceptable safety in mild-moderate COVID-19 infection. Objectives: The primary objective of the study was to evaluate the effectiveness of favipiravir in moderate COVID-19 patients, while the secondary objective was to determine the safety of favipiravir. Materials and methods: We retrospectively analyzed medical records of favipiravir-treated COVID-19 cases from 3 centers to capture key details of moderate COVID-19 patients including medical history, symptoms, supportive treatment, and clinical outcome. The protocol of the study was approved by Independent Ethics Committee. Results: Data from medical records of 193 patients was available for analysis, including 54 patients of moderate severity. The mean age was 59.94 ± 13.18 years. 58.92% of the patients were male. Hypertension (78.57%) and diabetes (55.35%) were the two most prevalent comorbidities. Majority (85.71%) of patients had at least one comorbidity, while 66.07% had ≥2 comorbidities. Mean SpO2 was 92.83 ± 1.88% with a median of 93% (90-98). The most common clinical features were fever (87.5%), cough (80.35%), dyspnoea (57.14%) and myalgia (48.12%). The mean CRP was 65.58 ± 34.74 with a median of 57.85 (1.20 to 151) and the mean d-Dimer was 1082.95 ± 1129.7 with a median of 815 (156-7435). Favipiravir has been used for an average duration of 12.30 ± 3.99 days, with median duration of 14 days (1-14 days). The rate of clinical improvement on days 3, 5, 7 and 10 was 30.35%, 75%, 89.29% and 96.42%. Fever and dyspnoea were fully resolved by day 7 in all enrolled patients, while myalgia was resolved by day 10 in all patients and cough was resolved by day 10 in 97.77% of patients. Corticosteroid was used in 37.5% patients. Oxygen requirements on days 3, 5, 7 and 10 were 28.57%, 14.28%, 8.92% and 7.14% patients respectively. Progression of the disease was seen in 10.71% of cases. Overall favipiravir was well tolerated with few commonly reported adverse events like diarrhoea and nausea, which does not require drug discontinuation. 91.07% patients and physician rated favipiravir as good or very good on global assessment scale. Discussions An open-labeled nonrandomized study1 from China compared the effect of favipiravir (day 1 1,600 mg twice daily;days 2-14 600 mg twice daily) vs lopinavir/ritonavir (day 1-14 400/100 twice daily) in the treatment of COVID-19. Compared with the lopinavir/ritonavir arm, however, patients in the favipiravir arm showed a statistically significant shorter median length of time to viral clearance (4 vs 11 days, p < 0.001), improvement in chest CT findings at day 14 after randomization (91.4 vs 62.2%, p = 0.004), and lower incidence of adverse effects (11.43 vs 55.56%, p < 0.001). Chen et al.2 had conducted a prospective, open-label multicentric trial in China to compare two treatment arms in the management of clinically confirmed COVID-19 (maximum duration of symptom onset before randomization 12 days). Post hoc analysis demonstrated that favipiravir-treated patients showed a trend toward clinical improvement at day 7 among those with moderate COVID-19 (71.43 vs 55.86%, 95% CI 0.0271 to 0.2843, p = 0.0199) and earlier resolution of fever and cough (p < 0.0001). A Japanese observational study group recorded the details of hospitalized COVID-19 patients in Japan to assess the safety and efficacy of favipiravir. In >90% of cases, favipiravir was administered at a dose of 1,800 mg orally on ay 1 followed by 800 mg twice daily on subsequent days. The median duration of therapy was 11 days. Rates of clinical improvement at 7 and 14 days were 73.8 and 87.8%, 66.6 and 84.5%, and 40.1 and 60.3% for mild, moderate, and severe disease, respectively. Thus, the vast majority of patients with mild and moderate disease recovered from the illness. Conclusion: Approximately 90% clinical resolution rate in moderate COVID-19 patients in real-world settings supports its role in the management of hospitalized patients. Reduction in the oxygen requirement highlights its protective role against disease progression. Overall favipiravir was found to be effective and safe in the management of moderate COVID-19.