Outcomes and Healthcare Resource Utilization in Patients with COVID-19 Treated with Nirmatrelvir-Ritonavir: Real-World Data Analysis

Overview

Journal J Clin Med

Specialty General Medicine

Date 2024 Oct 26

PMID 39458042

Authors

Clara Weil

Lilac Tene

Gabriel Chodick

Noga Fallach

Wajeeha Ansari

Tal Distelman-Menachem

Yasmin Maor

Affiliations

Soon will be listed here.

Abstract

Nirmatrelvir-ritonavir was granted emergency use authorization in Israel in January 2022 to treat high-risk patients with mild-to-moderate COVID-19. The aim of the study was to assess the association between nirmatrelvir-ritonavir treatment and COVID-19-related hospitalization and healthcare resource utilization (HCRU) in a country with a high level of vaccinations compared to patients who were offered treatment and declined. The Maccabi Healthcare Services dataset was used to identify high-risk SARS-CoV-2-positive adults from January to February 2022 who received nirmatrelvir-ritonavir within 5 days of symptom onset (treatment group) or who were offered nirmatrelvir-ritonavir treatment and declined it (reference group). COVID-19-related hospitalizations and all-cause mortality and HCRU within 30 days were compared between treatment and reference groups using inverse probability of treatment weighting. Treatment and reference groups included 3460 (median age, 68.4 years) and 1654 (70.2 years) patients, respectively. Patients with ≥1 dose of COVID-19 vaccine accounted for 89.5% (treatment group) and 72.1% (reference group) of the total. Treatment was associated with a lower risk of COVID-19-related hospitalization (adjusted OR, 0.59 [95% CI, 0.41,0.83]). Results were similar by age group (18-64/≥65 years) and among patients with/without vaccination in the prior 180 days. There were 11 (0.3%) versus 11 (0.7%) deaths in the treatment and reference groups, respectively. Treated patients had lower inpatient HCRU and greater less intensive outpatient HCRU (e.g., telemedicine and emergency room visits). Nirmatrelvir-ritonavir treatment was associated with a reduced risk of COVID-19-related hospitalization and a shift to less intensive outpatient HCRU. Comparison with a reference group of nirmatrelvir-ritonavir-eligible patients who declined treatment enabled an unbiased outcome assessment. Real-world data gathered during the Omicron BA.1 variant wave of COVID-19 in Israel support the continued use of nirmatrelvir-ritonavir for high-risk adults of all ages, regardless of previous vaccinations.

References

Weitzman D, Chodick G, Shalev V, Grossman C, Grossman E . Prevalence and factors associated with resistant hypertension in a large health maintenance organization in Israel. Hypertension. 2014; 64(3):501-7. DOI: 10.1161/HYPERTENSIONAHA.114.03718. View

Rossman H, Shilo S, Meir T, Gorfine M, Shalit U, Segal E . COVID-19 dynamics after a national immunization program in Israel. Nat Med. 2021; 27(6):1055-1061. DOI: 10.1038/s41591-021-01337-2. View

Sevrioukova I, Poulos T . Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir. Proc Natl Acad Sci U S A. 2010; 107(43):18422-7. PMC: 2973003. DOI: 10.1073/pnas.1010693107. View

Anand K, Ziebuhr J, Wadhwani P, Mesters J, Hilgenfeld R . Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science. 2003; 300(5626):1763-7. DOI: 10.1126/science.1085658. View

Owen D, Allerton C, Anderson A, Aschenbrenner L, Avery M, Berritt S . An oral SARS-CoV-2 M inhibitor clinical candidate for the treatment of COVID-19. Science. 2021; 374(6575):1586-1593. DOI: 10.1126/science.abl4784. View

Bar-On Y, Goldberg Y, Mandel M, Bodenheimer O, Freedman L, Kalkstein N . Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel. N Engl J Med. 2021; 385(15):1393-1400. PMC: 8461568. DOI: 10.1056/NEJMoa2114255. View

Quinn S, Hilyard K, Castaneda-Angarita N, Freimuth V . Public acceptance of peramivir during the 2009 H1N1 influenza pandemic: implications for other drugs or vaccines under emergency use authorizations. Disaster Med Public Health Prep. 2015; 9(2):166-74. DOI: 10.1017/dmp.2014.156. View

Wai A, Chan C, Cheung A, Wang K, Chan S, Lee T . 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. 2022; 30:100602. PMC: 9532222. DOI: 10.1016/j.lanwpc.2022.100602. View

Henderson H, Wohl D, Fischer W, Bartelt L, van Duin D, Agil D . COVID-19 hospitalization risk after outpatient nirmatrelvir/ritonavir use, January to August 2022, North Carolina. J Antimicrob Chemother. 2024; 79(4):859-867. PMC: 10984939. DOI: 10.1093/jac/dkae042. View

10.

Chodick G, Heymann A, Shalev V, Kookia E . The epidemiology of diabetes in a large Israeli HMO. Eur J Epidemiol. 2004; 18(12):1143-6. DOI: 10.1023/b:ejep.0000006635.36802.c8. View

11.

Coresh J, Turin T, Matsushita K, Sang Y, Ballew S, Appel L . Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality. JAMA. 2014; 311(24):2518-2531. PMC: 4172342. DOI: 10.1001/jama.2014.6634. View

12.

Shah M, Joyce B, Plumb I, Sahakian S, Feldstein L, Barkley E . Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19 - United States, April-September 2022. MMWR Morb Mortal Wkly Rep. 2022; 71(48):1531-1537. PMC: 9721144. DOI: 10.15585/mmwr.mm7148e2. View

13.

Shalev V, Chodick G, Goren I, Silber H, Kokia E, Heymann A . The use of an automated patient registry to manage and monitor cardiovascular conditions and related outcomes in a large health organization. Int J Cardiol. 2010; 152(3):345-9. DOI: 10.1016/j.ijcard.2010.08.002. View

14.

Yoshida K, Solomon D, Kim S . Active-comparator design and new-user design in observational studies. Nat Rev Rheumatol. 2015; 11(7):437-41. PMC: 4486631. DOI: 10.1038/nrrheum.2015.30. View

15.

Wong C, Au I, Lau K, Lau E, Cowling B, Leung G . Real-world effectiveness of early molnupiravir or nirmatrelvir-ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study. Lancet Infect Dis. 2022; 22(12):1681-1693. PMC: 9401976. DOI: 10.1016/S1473-3099(22)00507-2. View

16.

Abraham S, Nohria A, Neilan T, Asnani A, Saji A, Shah J . Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19: JACC Review Topic of the Week. J Am Coll Cardiol. 2022; 80(20):1912-1924. PMC: 9580069. DOI: 10.1016/j.jacc.2022.08.800. View

17.

Arbel R, Sagy Y, Hoshen M, Battat E, Lavie G, Sergienko R . Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge. N Engl J Med. 2022; 387(9):790-798. PMC: 9454652. DOI: 10.1056/NEJMoa2204919. View

18.

Shi C, Qiu L, Zhuo J, Fang Y, Wang L, Xia J . Prevalence of inappropriate use of nirmatrelvir-ritonavir antiviral therapy in hospitalized patients: A multi-centre retrospective study in China. Int J Antimicrob Agents. 2023; 62(2):106857. PMC: 10197429. DOI: 10.1016/j.ijantimicag.2023.106857. View

19.

Ganatra S, Dani S, Ahmad J, Kumar A, Shah J, Abraham G . Oral Nirmatrelvir and Ritonavir in Nonhospitalized Vaccinated Patients With Coronavirus Disease 2019. Clin Infect Dis. 2022; 76(4):563-572. PMC: 9452095. DOI: 10.1093/cid/ciac673. View

20.

Torge D, Bernardi S, Arcangeli M, Bianchi S . Histopathological Features of SARS-CoV-2 in Extrapulmonary Organ Infection: A Systematic Review of Literature. Pathogens. 2022; 11(8). PMC: 9415619. DOI: 10.3390/pathogens11080867. View