https://doi.org/10.4081/itjm.2024.1737
Prevention is better than healing. Clinical and economic implications of oral antiviral agents in COVID-19: a prospective study
Published: 3 June 2024
Abstract Views: 534
PDF: 331
HTML: 27
HTML: 27
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
COVID-19 represents a threat for frailty patients. This study compares molnupiravir and nirmatrelvir for fragile COVID- 19 patients' efficacy, safety, and cost. An observational, prospective study allowed us to evaluate molnupiravir’s efficacy and safety in real life, compare it to a subgroup of patients treated with nirmatrelvir-ritonavir, and analyze its cost-effectiveness. From January to December 2022, 435 patients (225 males, 220 females; median age 72 years), were enrolled; 24 patients were unvaccinated, and 280 patients had ≥2 risk factors. Molnupiravir performed better clinically and economically. Compared to literature data, in these patients, hospitalization was 2.5% vs. 6.8% (P<0.005), overall adverse effects 14,3% vs. 30.4% (P<0.0001), severe adverse effects 2.6 vs. 6.9% (P<0.001), thus involving potential total savings of about € 92.954 per patient (8% of standard of care cost). Early molnupiravir treatment helped fragile patients who partially responded to the vaccine, or with absolute contraindications to vaccination, to overcome COVID-19 without the need for hospitalization. In elderly patients with multiple pathologies and multiple drugs, molnupiravir prevents disease progression clinically and economically.
Rosiello DF, Anwar S, Yufika A, et al. Acceptance of COVID-19 vaccination at different hypothetical efficacy and safety levels in ten countries in Asia, Africa, and South America. Narra J 2021;1.
DOI: https://doi.org/10.52225/narra.v1i3.55
Vinci A, Pasquarella A, Corradi MP, et al. Emergency medical services calls analysis for trend prediction during epidemic outbreaks: interrupted time series analysis on 2020-2021 COVID-19 epidemic in Lazio, Italy. Int J Environ Res Public Health 2022;19:5951.
DOI: https://doi.org/10.3390/ijerph19105951
Alfonsi V, Scarpelli S, Gorgoni M, et al. Healthcare workers after two years of COVID-19: the consequences of the pandemic on psychological health and sleep among nurses and physicians. Int J Environ Res Public Health 2023;20:1410.
DOI: https://doi.org/10.3390/ijerph20021410
Pietrantonio F, Rosiello F, Alessi E, et al. Burden of COVID-19 on Italian internal medicine wards: Delphi, SWOT, and performance analysis after two pandemic waves in the local health authority “Roma 6” hospital structures. Int J Environ Res Public Health 2021;18:5999.
DOI: https://doi.org/10.3390/ijerph18115999
Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 2020;20:533-4.
DOI: https://doi.org/10.1016/S1473-3099(20)30120-1
Johns Hopkins Coronavirus Resource Center. Available from: https://www.who.int/publications/m/item/weeklyepidemiological-update-on-covid-19
Huy NT, Chico RM, Huan VT, et al. Awareness and preparedness of healthcare workers against the first wave of the COVID-19 pandemic: a cross-sectional survey across 57 countries. Gesser-Edelsburg A (ed.). PLOS ONE 2021;16:e0258348.
Harapan H, Yufika A, Anwar S, et al. Beliefs on social distancing and face mask practices during the COVID-19 pandemic in low- and middle-income countries: a cross-sectional study. F1000Research 2022;11:206.
DOI: https://doi.org/10.12688/f1000research.79534.1
Salzberger B, Buder F, Lampl B, et al. Epidemiology of SARS-CoV-2. Infection 2021;49:233-9.
DOI: https://doi.org/10.1007/s15010-020-01531-3
Fahriani M, Ilmawan M, Fajar JK, et al. Persistence of long COVID symptoms in COVID-19 survivors worldwide and its potential pathogenesis - A systematic review and meta-analysis. Narra J 2021;1.
DOI: https://doi.org/10.52225/narraj.v1i2.36
Fajar JK, Ilmawan M, Mamada S, et al. Global prevalence of persistent neuromuscular symptoms and the possible pathomechanisms in COVID-19 recovered individuals: A systematic review and meta-analysis. Narra J 2021;1.
DOI: https://doi.org/10.52225/narra.v1i3.48
Harapan H, Anwar S, Yufika A, et al. Vaccine hesitancy among communities in ten countries in Asia, Africa, and South America during the COVID-19 pandemic. Pathog Glob Health 2021;1-8.
Rosiello F, D’Oca E. Vaccinations and the movement of antivaccers. Eur J Public Health 2020;30.
DOI: https://doi.org/10.1093/eurpub/ckaa166.700
Takashita E, Kinoshita N, Yamayoshi S, et al. Efficacy of antibodies and antiviral drugs against COVID-19 omicron variant. N Engl J Med 2022;386:995-8.
DOI: https://doi.org/10.1056/NEJMc2119407
Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of COVID-19 — Final Report. N Engl J Med 2020;383:1813-26.
DOI: https://doi.org/10.1056/NEJMc2022236
Gottlieb RL, Vaca CE, Paredes R, et al. Early remdesivir to prevent progression to severe COVID-19 in outpatients. N Engl J Med 2022;386:305-15.
DOI: https://doi.org/10.1056/NEJMoa2116846
Drożdżal S, Rosik J, Lechowicz K, et al. An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment. Drug Resist Updat 2021;59:100794.
DOI: https://doi.org/10.1016/j.drup.2021.100794
FDA. Coronavirus (COVID-19) Update: FDA Authorizes First Oral Antiviral for Treatment of COVID-19. 2021. Available from: https://www.fda.gov/news-events/pressannouncements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19
Hashemian SMR, Sheida A, Taghizadieh M, et al. Paxlovid (Nirmatrelvir/Ritonavir): a new approach to COVID-19 therapy? Biomed Pharmacother 2023;162:114367.
DOI: https://doi.org/10.1016/j.biopha.2023.114367
Cox RM, Wolf JD, Plemper RK. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nat Microbiol 2021;6:11-8.
DOI: https://doi.org/10.1038/s41564-020-00835-2
Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19. N Engl J Med 2022;386:1397-408.
DOI: https://doi.org/10.1056/NEJMoa2118542
Pietrantonio F, Ciamei A, Vinci A, et al. Polypharmacy management in a gender perspective: at the heart of the problem: analysis of major cardiac diseases, SARS-CoV-2 affection and gender distribution in a cohort of patients in internal medicine ward. Int J Environ Res Public Health 2023;20:5711.
DOI: https://doi.org/10.3390/ijerph20095711
Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of COVID-19 in non-hospitalized patients. N Engl J Med 2022;386:509-20.
DOI: https://doi.org/10.1056/NEJMoa2116044
AIFA. Modifiche al registro degli antivirali orali contro il COVID 19. Available from: https://www.aifa.gov.it/-/modifica-registro-antivirali-orali-covid-19
Ruggeri M, Drago C, Rosiello F, et al. Economic evaluation of treatments for migraine: an assessment of the generalizability following a systematic review. PharmacoEconomics 2020;38:473-84.
DOI: https://doi.org/10.1007/s40273-019-00879-1
National Library of Medicine. Cost effectiveness analysis. 2023. Available from: https://www.ncbi.nlm.nih.gov/mesh/?term=cost+effectiveness
Ruggeri M, Signorini A, Caravaggio S, et al. Cost-effectiveness analysis of tapentadol versus oxycodone/naloxone in both branded and generic formulations in patients with musculoskeletal pain. Clin Drug Investig 2021;41:875-83.
DOI: https://doi.org/10.1007/s40261-021-01074-x
Agenzia Nazionale per i Servizi Sanitari Regionali. Rapporto COVID-19. 2020. Available from: https://www.agenas.gov.it/comunicazione/primo-piano/2112-agenase-istat-impatto-dell%E2%80%99epidemia-covid-19-sul-sistema-ospedaliero-italiano-anno-2020 (accessed on 01/06/24).
Istituto Superiore di Sanità. Speciale COVID-19. Varianti COVID. Available from: https://www.iss.it/cov19-cosafa-iss-varianti
Ruggeri M, Signorini A, Drago C, et al. Model for estimating the healthcare costs and capacity of intensive care units in Italy in the treatment of patients with COVID-19: remdesivir impact assessment. AboutOpen 2020;7:95-102.
DOI: https://doi.org/10.33393/abtpn.2020.2213
Ruggeri M, Signorini A, Caravaggio S, et al. Estimation Model for healthcare costs and intensive care units access for COVID-19 patients and evaluation of the effects of remdesivir in the portuguese context: hypothetical study. Clin Drug Investig 2022;42:345-54.
DOI: https://doi.org/10.1007/s40261-022-01128-8
von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007;370:1453-7.
DOI: https://doi.org/10.1016/S0140-6736(07)61602-X
von Elm E, Altman DG, Egger M, et al. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ 2007;335:806-8.
DOI: https://doi.org/10.1136/bmj.39335.541782.AD
Pietrantonio F, Vinci A, Rosiello F, et al. Green line hospital territory study: a single-blind randomized clinical trial for evaluation of technological challenges of continuous wireless monitoring in internal medicine, preliminary results. Int J Environ Res Public Health 2021;18:10328.
DOI: https://doi.org/10.3390/ijerph181910328
Singh AK, Singh A, Singh R, Misra A. Molnupiravir in COVID-19: a systematic review of literature. Diabetes Metab Syndr Clin Res Rev 2021;15:102329.
DOI: https://doi.org/10.1016/j.dsx.2021.102329
Sendi P, Razonable RR, Nelson SB, et al. First-generation oral antivirals against SARS-CoV-2. Clin Microbiol Infect 2022;28:1230-5.
DOI: https://doi.org/10.1016/j.cmi.2022.04.015
Kaore S, Atal S. Molnupiravir in COVID-19: a scoping review. Curr Drug Res Rev 2022;14:203-14.
DOI: https://doi.org/10.2174/2589977514666220527105158
Singh AK, Singh A, Singh R, Misra A. An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19. Diabetes Metab Syndr Clin Res Rev 2022;16:102396.
DOI: https://doi.org/10.1016/j.dsx.2022.102396
Mali KR, Eerike M, Raj GM, et al. Efficacy and safety of Molnupiravir in COVID-19 patients: a systematic review. Ir J Med Sci 2022;192:1665-78.
DOI: https://doi.org/10.1007/s11845-022-03139-y
Kamal L, Ramadan A, Farraj S, et al. The pill of recovery; Molnupiravir for treatment of COVID-19 patients; a systematic review. Saudi Pharm J 2022;30:508-18.
DOI: https://doi.org/10.1016/j.jsps.2022.03.002
Lai CC, Wang YH, Chen KH, et al. The clinical efficacy and safety of anti-viral agents for non-hospitalized patients with COVID-19: a systematic review and network meta-analysis of randomized controlled trials. Viruses 2022;14:1706.
DOI: https://doi.org/10.3390/v14081706
Yip TCF, Lui GCY, Lai MSM, 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:e26-33.
DOI: https://doi.org/10.1093/cid/ciac687
Wen W, Chen C, Tang J, et al. Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19: a meta-analysis. Ann Med 2022;54:516-23.
DOI: https://doi.org/10.1080/07853890.2022.2034936
Vena A, Traman L, Bavastro M, et al. Early clinical experience with molnupiravir for mild to moderate breakthrough COVID-19 among fully vaccinated patients at risk for disease progression. Vaccines 2022;10:1141.
DOI: https://doi.org/10.3390/vaccines10071141
Gentile I, Scotto R, Schiano Moriello N, et al. Nirmatrelvir/ ritonavir and molnupiravir in the treatment of mild/moderate COVID-19: results of a real-life study. Vaccines 2022;10:1731.
DOI: https://doi.org/10.3390/vaccines10101731
Ruggeri M, Signorini A, Caravaggio S, et al. Modeling the Potential Impact of Remdesivir Treatment for Hospitalized Patients with COVID-19 in Saudi Arabia on healthcare resource use and direct hospital costs: a hypothetical study. Clin Drug Investig 2022;42:669-78.
DOI: https://doi.org/10.1007/s40261-022-01177-z
Goswami H, Alsumali A, Jiang Y, et al. Cost-effectiveness analysis of molnupiravir versus best supportive care for the treatment of outpatient COVID-19 in adults in the US. PharmacoEconomics 2022;40:699-714.
DOI: https://doi.org/10.1007/s40273-022-01168-0
Onen-Dumlu Z, Harper AL, Forte PG, et al. Optimising the balance of acute and intermediate care capacity for the complex discharge pathway: Computer modelling study during COVID-19 recovery in England. Pietrantonio F, (ed.). PLOS ONE 2022;17:e0268837.
DOI: https://doi.org/10.1371/journal.pone.0268837
Liu J, Pan X, Zhang S, et al. Efficacy and safety of Paxlovid in severe adult patients with SARS-CoV-2 infection: a multicenter randomized controlled study. Lancet Reg Health West Pac 2023;33:100694.
DOI: https://doi.org/10.1016/j.lanwpc.2023.100694
Husereau D, Drummond M, Augustovski F, et al. Consolidated health economic evaluation reporting standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations. Value Health 2022;25:3-9.
DOI: https://doi.org/10.1016/j.jval.2021.11.1351
Wise J. COVID-19: molnupiravir does not cut hospital admissions or deaths in vaccinated people at high risk, trial finds. BMJ 2022;379:o3055.
DOI: https://doi.org/10.1136/bmj.o3055
Scioscia G, De Pace CC, Giganti G, et al. Real life experience of molnupiravir as a treatment of SARS-CoV-2 infection in vaccinated and unvaccinated patients: a letter on its effectiveness at preventing hospitalization. Ir J Med Sci 2022;1922301-3.
DOI: https://doi.org/10.1007/s11845-022-03241-1
Khoo SH, FitzGerald R, Saunders G, et al. 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;23:183-95.
DOI: https://doi.org/10.1016/S1473-3099(22)00644-2
Parums DV. Editorial: long COVID, or post-COVID syndrome, and the global impact on health care. Med Sci Monit 2021;27.
DOI: https://doi.org/10.12659/MSM.933446
Fischer WA, Eron JJ, Holman W, 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;14:eabl7430.
DOI: https://doi.org/10.1126/scitranslmed.abl7430
How to Cite
Pietrantonio, F., Rosiello, F., Ruggeri, M., Cattaruzza, M. S., Vinci, A., Lordi, M., & Cipriano, E. (2024). Prevention is better than healing. Clinical and economic implications of oral antiviral agents in COVID-19: a prospective study. Italian Journal of Medicine, 18(2). https://doi.org/10.4081/itjm.2024.1737
Copyright (c) 2024 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.