Should molnupiravir be used for covid-19 outpatient management in individuals at high risk for disease severity?
A systematic review and meta-analysis of randomized controlled trials
DOI:
https://doi.org/10.1590/Keywords:
Molnupiravir, COVID-19, High-risk patientsAbstract
There is currently no consensus on whether to initiate molnupiravir treatment for all outpatients at high risk of severe SARS-CoV-2 infection. PubMed, Embase and Cochrane databases were systematically searched for studies that allocated COVID-19 high-risk, non-hospitalized patients to molnupiravir or a control. We computed risk ratios (RR) for binary endpoints, with 95% confidence intervals (CI), random effects model was used and a p-value <0.05 was considered as statistically significant. We analyzed data into Review Manager 5.4. We included seven randomized studies, with total of 31,569 patients , of whom 15,706 (50.8%) underwent molnupiravir therapy. Molnupiravir therapy was associated with a significant reduction in all-cause mortality rate in this population compared with control (RR 0.31; 95% CI 0.12–0.80; P= 0.02; I 2: 0%) and in hospital admission (RR 0.79; 95% CI 0.66–0.94; P= 0.007; I 2: 47%). The use of molnupiravir was not associated with a significant reduction of all-cause mortality or hospital admission for subgroups including only patients with cardiovascular disease (RR 0.79; 95% CI 0.45–1.39; P= 0.41; I2: 0%) and diabetes (RR 0.85; 95% CI 0.51–1.42; P= 0.32; I2: 0%). Our results suggest that molnupiravir use might be considered in high-risk of severity disease, non-hospitalized patients.
Downloads
References
Amani B, Zareei S, Amani B. Rapid review and meta-analysis of adverse events associated with molnupiravir in patients with COVID-19. Br J Clin Pharmacol. 2022;88(10):4403-4411.
Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64:401–6. 22.
Beran A, Mhanna A, Mhanna M, Farrow D, Sidiki S, Khader Y, et. al. Molnupiravir for the Treatment of Coronavirus Disease 2019: A Systematic Review With Meta-Analysis of 12,451 Patients. Am J Ther. 2024 Jan-Feb 01;31(1):e47-e50. doi: 10.1097/MJT.0000000000001541.
» https://doi.org/10.1097/MJT.0000000000001541
Butler CC, Hobbs FDR, Gbinigie OA, Rahman NM, Hayward G, Richards DB, et al. PANORAMIC Trial Collaborative Group. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet. 2023;401(10373):281-293.
Cegolon L, Pol R, Simonetti O, Larese Filon F, Luzzati R. Molnupiravir, Nirmatrelvir/Ritonavir, or Sotrovimab for High-Risk COVID-19 Patients Infected by the Omicron Variant: Hospitalization, Mortality, and Time until Negative Swab Test in Real Life. Pharmaceuticals (Basel). 2023;16(5):721.
Deeks JJ, Higgins JPT, Altman DG, Higgins JPT, Thomas J, Chandler J, et. al. Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et. al. Cochrane Handbook for Systematic Reviews of Interventions version 6.2. 2023.
Fischer WA 2nd, Eron JJ Jr, Holman W, Cohen MS, Fang L, Szewczyk LJ, et. al. A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus. Sci Transl Med. 2022 Jan 19;14(628):eabl7430.
Gao Y, Liu M, Li Z, Xu J, Zhang J, Tian J. Molnupiravir for treatment of adults with mild or moderate COVID-19: a systematic review and meta-analysis of randomized controlled trials. Clin Microbiol Infect. 2023;29(8):979-999.
Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions. Cochrane. 2023.
Huang C, Lu TL, Lin L. Real-World Clinical Outcomes of Molnupiravir for the Treatment of Mild to Moderate COVID-19 in Adult Patients during the Dominance of the Omicron Variant: A Meta-Analysis. Antibiotics (Basel). 2023 Feb 15;12(2):393. doi: 10.3390/antibiotics12020393.
» https://doi.org/10.3390/antibiotics12020393.
Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, et al. MOVe-OUT Study Group. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022;386(6):509-520
Khoo SH, Fitzgerald R, Fletcher T, Ewings S, Jaki T, Lyon R, et al. Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a phase I, open-label, dose-escalating, randomized controlled study. J Antimicrob Chemother. 2021;76:3286–3295.
Khoo SH, FitzGerald R, Saunders G, Middleton C, Ahmad S, Edwards CJ, et al. AGILE CST-2 Study Group. Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Infect Dis. 2023;23(2):183-195.
Lui DTW, Chung MSH, Lau EHY, Lau KTK, Au ICH, Lee CH, et al. Analysis of All-Cause Hospitalization and Death Among Nonhospitalized Patients With Type 2 Diabetes and SARS-CoV-2 Infection Treated With Molnupiravir or Nirmatrelvir-Ritonavir During the Omicron Wave in Hong Kong. JAMA Netw Open. 2023;6(5):e2314393.
Mali KR, Eerike M, Raj GM, Bisoi D, Priyadarshini R, Ravi G, et al. Efficacy and safety of Molnupiravir in COVID-19 patients: a systematic review. Ir J Med Sci. 2023 Aug;192(4):1665-1678. doi: 10.1007/s11845-022-03139-y.
» https://doi.org/10.1007/s11845-022-03139-y.
Malin JJ, Weibel S, Gruell H, Kreuzberger N, Stegemann M, Skoetz N. Efficacy and safety of molnupiravir for the treatment of SARS-CoV-2 infection: a systematic review and meta-analysis. J Antimicrob Chemother. 2023 Jul 5;78(7):1586-1598. doi: 10.1093/jac/dkad132.
» https://doi.org/10.1093/jac/dkad132.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.
Pourkarim F, Pourtaghi-Anvarian S, Rezaee H. Molnupiravir: A new candidate for COVID-19 treatment. Pharmacol Res Perspect. 2022;10(1):e00909.
Rufaida MT, Kedwai I, Ahsan F, Ahsan F, Shamim A, Shariq M, et al. A dossier on COVID-19 chronicle. J Basic Clin Physiol Pharmacol. 2021;33(1):45-54.
Sinha S, N K, Suram VK, Chary SS, Naik S, Singh VB, et al. Efficacy and safety of molnupiravir in mild COVID-19 patients in India. Cureus. 2022 Nov 14;14(11):e31508. doi: 10.7759/cureus.31508.
» https://doi.org/10.7759/cureus.31508.
Singh AK, Singh A, Singh R, Misra A. Molnupiravir in COVID-19: A systematic review of literature. Diabetes Metab Syndr. 2021;15(6):102329.
Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.
Sun M, Lai H, Huang J, Liu J, Li Y, Tian J, et al. Molnupiravir for the treatment of non-severe COVID-19: a systematic review and meta-analysis of 14 randomized trials with 34 570 patients. J Antimicrob Chemother. 2023 Sep 5;78(9):2131-2139. doi: 10.1093/jac/dkad216.
» https://doi.org/10.1093/jac/dkad216.
Tian L, Pang Z, Li M, Lou F, An X, Zhu S, et al. Molnupiravir and Its Antiviral Activity Against COVID-19. Front Immunol. 2022;13:855496.
Tippabhotla SK, Lahiri S, D RR, Kandi C, V NP. Efficacy and safety of molnupiravir for the treatment of non-hospitalized adults with mild COVID-19: A randomized, open-label, parallel-group phase 3 trial. [Posted: 24 Feb 2022. Available at SSRN: https://ssrn.com/abstract=4042673 or ( https://dx.doi.org/10.2139/ssrn.4042673 )
» https://doi.org/10.2139/ssrn.4042673
» https://ssrn.com/abstract=4042673
» https://dx.doi.org/10.2139/ssrn.4042673
Xie Y, Bowe B, Al-Aly Z. Molnupiravir and risk of hospital admission or death in adults with covid-19: emulation of a randomized target trial using electronic health records. BMJ. 2023;380: e072705.
Wai AK, Chan CY, Cheung AW, Wang K, Chan SC, Lee TT, et al. Association of Molnupiravir and Nirmatrelvir-Ritonavir with preventable mortality, hospital admissions and related avoidable healthcare system cost among high-risk patients with mild to moderate COVID-19. Lancet Reg Health West Pac. 2023;30:100602.
Wen W, Chen C, Tang J, Wang C, Zhou M, Cheng Y, et al. Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19:a meta-analysis. Ann Med. 2022;54(1):516-523.
WHO coronavirus (COVID-19) dashboard. Geneva: World Health Organization, 2023. ( https://covid19.who.int/ ).
WHO COVID-19 case definitions. Geneva: World Health Organization, December16, 2020 ( https://apps.who.int/iris/rest/bitstreams/1322790/retrieve) .
» https://apps.who.int/iris/rest/bitstreams/1322790/retrieve)
Wong CKH, Au ICH, Lau KTK, Lau EHY, Cowling BJ, Leung GM. Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir against mortality, hospitalization, and in-hospital outcomes among community-dwelling, ambulatory COVID-19 patients during the BA.2.2 wave in Hong Kong: An observational study. MedRxiv 2022.
Yip TC, Lui GC, Lai MS, Wong VW, Tse YK, Ma BH, et al. Impact of the use of oral antiviral agents on the risk of hospitalization in community coronavirus disease 2019 patients (COVID-19). Clin Infect Dis. 2023;76(3):e26-e33.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Brazilian Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on-line journal has open and free access.