Prevention is better than healing. Clinical and economic implications of oral antiviral agents in COVID-19: a prospective study

Published: 3 June 2024
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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.

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Citations

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