Effectiveness of Favipiravir Monotherapy in the Treatment of COVID-19: Real World Data Analysis from Thailand

Overview

Journal Lancet Reg Health Southeast Asia

Date 2023 Feb 13

PMID 36776761

Authors

Attasit Srisubat

Somchai Thanasitthichai

Subsai Kongsaengdao

Narong Maneeton

Benchalak Maneeton

Somsak Akksilp

Affiliations

Soon will be listed here.

Abstract

Background: Previous studies showed that Favipiravir, a selective viral ribonucleic acid dependent-ribonucleic acid polymerase inhibitor, exhibited a trend of clinical improvement within 14 days and promoted viral clearance by day 7, without reduction of mortality rate in COVID-19.

Methods: During the COVID-19 pandemic, Department of Medical Services (Thailand) formulated National Clinical Treatment Guidelines for COVID-19 and approved Favipiravir to eight medical centres. After treatment with Favipiravir monotherapy, we compared real-world data analysis to supportive treatment without antiviral agents.

Findings: We analysed 12,888 COVID-19 patients between June 1, 2021, and July 31, 2021. This group study excluded 66 asymptomatic and 4634 COVID-19 patients treated with other antiviral agents. The 4896 mild, 2357 moderate, and 935 severe COVID-19 patients were analysed. All patients neither had previous SARS-CoV-2 infection nor received an mRNA vaccine during study period. Favipiravir monotherapy reduced the 28-day mortality risk in severe COVID-19 by relative risk (RR) = 0.72 (95% CI 0.58-0.91 P = 0.006) after adjustment for aging and hypertension. However, in mild and moderate COVID-19, Favipiravir monotherapy did not significantly reduce 28-day mortality risk by RR = 0.59 (95% CI 0.06-5.43 P = 0.65) after adjustment for aging, and RR = 0.60 (95% CI 0.32-1.13 P = 0.11) after adjustment for aging and obesity, respectively. In the patient with recovery, Favipiravir monotherapy exhibited a shortening time to recovery when compared to supportive treatment without antiviral agents (mean ± SD by 9.6 ± 7.1 vs. 12.9 ± 7.6 days: P < 0.0001, 10.0 ± 5.9 vs. 12.4 ± 5.3 days: P < 0.0001, and 11.2 ± 7.8 vs. 13.1 ± 8.0 days: P < 0.0001 in mild, moderate, and severe COVID-19 respectively).

Interpretation: Real-world data analysis showed that favipiravir monotherapy was superior to supportive treatment without antiviral agents in shortening the recovery time in surviving patients and significantly reducing 28-day mortality risk in severe COVID-19.

Funding: Department of Medical Services, Ministry of Public Health, Thailand.

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References

Zhao H, Zhu Q, Zhang C, Li J, Wei M, Qin Y . Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size. Biomed Pharmacother. 2020; 133:110825. PMC: 7524677. DOI: 10.1016/j.biopha.2020.110825. View

Hassanipour S, Arab-Zozani M, Amani B, Heidarzad F, Fathalipour M, Martinez-de-Hoyo R . The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials. Sci Rep. 2021; 11(1):11022. PMC: 8155021. DOI: 10.1038/s41598-021-90551-6. View

Khamis F, Al Naabi H, Al Lawati A, Ambusaidi Z, Al Sharji M, Al Barwani U . Randomized controlled open label trial on the use of favipiravir combined with inhaled interferon beta-1b in hospitalized patients with moderate to severe COVID-19 pneumonia. Int J Infect Dis. 2020; 102:538-543. PMC: 7833906. DOI: 10.1016/j.ijid.2020.11.008. View

Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J . Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering (Beijing). 2020; 6(10):1192-1198. PMC: 7185795. DOI: 10.1016/j.eng.2020.03.007. View

Jayk Bernal A, Gomes da Silva M, Musungaie D, Kovalchuk E, Gonzalez A, Delos Reyes V . Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2021; 386(6):509-520. PMC: 8693688. DOI: 10.1056/NEJMoa2116044. View

Ohno Y, Aoyagi K, Arakita K, Doi Y, Kondo M, Banno S . Newly developed artificial intelligence algorithm for COVID-19 pneumonia: utility of quantitative CT texture analysis for prediction of favipiravir treatment effect. Jpn J Radiol. 2022; 40(8):800-813. PMC: 8993669. DOI: 10.1007/s11604-022-01270-5. View

Ader F, Bouscambert-Duchamp M, Hites M, Peiffer-Smadja N, Mentre F, Burdet C . Final results of the DisCoVeRy trial of remdesivir for patients admitted to hospital with COVID-19. Lancet Infect Dis. 2022; 22(6):764-765. PMC: 9132543. DOI: 10.1016/S1473-3099(22)00295-X. View

Lou Y, Liu L, Yao H, Hu X, Su J, Xu K . Clinical Outcomes and Plasma Concentrations of Baloxavir Marboxil and Favipiravir in COVID-19 Patients: An Exploratory Randomized, Controlled Trial. Eur J Pharm Sci. 2020; 157:105631. PMC: 7585719. DOI: 10.1016/j.ejps.2020.105631. View

Dabbous H, Abd-Elsalam S, El-Sayed M, Sherief A, Ebeid F, Abd El Ghafar M . Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study. Arch Virol. 2021; 166(3):949-954. PMC: 7829645. DOI: 10.1007/s00705-021-04956-9. View

10.

Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W . Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022; 386(15):1397-1408. PMC: 8908851. DOI: 10.1056/NEJMoa2118542. View

11.

Deng W, Yang C, Yang S, Chen H, Qiu Z, Chen J . Evaluation of favipiravir in the treatment of COVID-19 based on the real-world. Expert Rev Anti Infect Ther. 2021; 20(4):555-565. PMC: 8787837. DOI: 10.1080/14787210.2022.2012155. View

12.

Chen P, Chao C, Lai C . Clinical efficacy and safety of favipiravir in the treatment of COVID-19 patients. J Infect. 2020; 82(5):186-230. PMC: 7721353. DOI: 10.1016/j.jinf.2020.12.005. View

13.

Rattanaumpawan P, Jirajariyavej S, Lerdlamyong K, Palavutitotai N, Saiyarin J . Real-World Effectiveness and Optimal Dosage of Favipiravir for Treatment of COVID-19: Results from a Multicenter Observational Study in Thailand. Antibiotics (Basel). 2022; 11(6). PMC: 9220013. DOI: 10.3390/antibiotics11060805. View

14.

Udwadia Z, Singh P, Barkate H, Patil S, Rangwala S, Pendse A . Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int J Infect Dis. 2020; 103:62-71. PMC: 7668212. DOI: 10.1016/j.ijid.2020.11.142. View

15.

Doi Y, Hibino M, Hase R, Yamamoto M, Kasamatsu Y, Hirose M . A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19. Antimicrob Agents Chemother. 2020; 64(12). PMC: 7674035. DOI: 10.1128/AAC.01897-20. View

16.

Ivashchenko A, Dmitriev K, Vostokova N, Azarova V, Blinow A, Egorova A . AVIFAVIR for Treatment of Patients With Moderate Coronavirus Disease 2019 (COVID-19): Interim Results of a Phase II/III Multicenter Randomized Clinical Trial. Clin Infect Dis. 2020; 73(3):531-534. PMC: 7454388. DOI: 10.1093/cid/ciaa1176. View