Economic impact of dapagliflozin in the management of chronic kidney disease in Italy: results from a micro-simulation model
DOI:
https://doi.org/10.33393/grhta.2024.3309Keywords:
Acute kidney injury, Chronic kidney disease, Cost, Dapagliflozin, End-stage kidney disease, Hearth failureAbstract
Background: Dapagliflozin, approved in the treatment of patients with chronic kidney disease (CKD), has demonstrated attenuation of CKD progression and a reduced risk of cardio-renal outcomes and all-cause mortality (ACM) versus placebo, in addition to standard of care (SoC). The aim of this economic evaluation was to assess the potential medical care cost offsets associated with reduced rates of cardio-renal outcomes in Italy.
Methods: A comparative micro-simulation model estimated the outcome-related costs of dapagliflozin plus SoC versus SoC alone over a 3-year horizon based on the DAPA-CKD trial. Incidence rates of end-stage kidney disease (ESKD), hospitalizations for heart failure (hHF), acute kidney injury (AKI) and ACM were estimated for a treated population of 90,564 patients. Associated direct medical costs for non-fatal events (ESKD, hHF and AKI) were calculated using available literature and national tariffs. The analysis was restricted to outcome-associated costs and did not consider the cost of drug treatments and disease management.
Results: Patients treated with dapagliflozin plus SoC experienced fewer incident events of ESKD (6,540 vs 9,751), hHF (2,146 vs 4,242), AKI (3,772 vs. 5,271) and ACM (5,780 vs 8,037) per 90,564 treated patients versus those treated with SoC alone. Reductions (–35,6%) in clinical events (ESKD, hHF and AKI) were associated with a 34.4% reduction in total costs (€ 170 million) over 3 years. The clinical effect of dapagliflozin on ESKD management accounted for a € 134.5 million reduction in total costs.
Conclusion: Based on the DAPA-CKD trial, dapagliflozin may prevent cardio-renal event incidence with a positive effect upon the Italian National Healthcare Service (NHS). Over three years, we estimated that dapagliflozin can reduce the Italian NHS expenditure associated with the management of ESKD, hHF and AKI events by 34.4% (€ 170 million).
Downloads
References
Levey AS, de Jong PE, Coresh J, et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int. 2011;80(1):17-28. https://doi.org/10.1038/ki.2010.483 PMID:21150873
Hill NR, Fatoba ST, Oke JL, et al. Global prevalence of chronic kidney disease—a systematic review and meta-analysis. PLoS One. 2016;11(7):e0158765. https://doi.org/10.1371/journal.pone.0158765 PMID:27383068
Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). 2022;12(1):7-11. https://doi.org/10.1016/j.kisu.2021.11.003 PMID:35529086
Lv JC, Zhang LX. Prevalence and disease burden of chronic kidney disease. Adv Exp Med Biol. 2019;1165:3-15. https://doi.org/10.1007/978-981-13-8871-2_1 PMID:31399958
Jager KJ, Kovesdy C, Langham R, Rosenberg M, Jha V, Zoccali C. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Nephrol Dial Transplant. 2019;34(11):1803-1805. https://doi.org/10.1093/ndt/gfz174 PMID:31566230
Hirst JA, Hill N, O’Callaghan CA, et al. Prevalence of chronic kidney disease in the community using data from OxRen: a UK population-based cohort study. Br J Gen Pract. 2020;70(693):e285-e293. https://doi.org/10.3399/bjgp20X708245 PMID:32041766
Abdul Sultan A, Wittbrodt E, Malvolti E, et al. POS-300 Patient-reported early stage chronic kidney disease. Kidney Int Rep. 2021;6(4):S129. https://doi.org/10.1016/j.ekir.2021.03.316
Baek SD, Baek CH, Kim JS, Kim SM, Kim JH, Kim SB. Does stage III chronic kidney disease always progress to end-stage renal disease? A ten-year follow-up study. Scand J Urol Nephrol. 2012;46(3):232-238. https://doi.org/10.3109/00365599.2011.649045 PMID:22545920
Pagels AA, Söderkvist BK, Medin C, Hylander B, Heiwe S. Health-related quality of life in different stages of chronic kidney disease and at initiation of dialysis treatment. Health Qual Life Outcomes. 2012;10(1):71. https://doi.org/10.1186/1477-7525-10-71 PMID:22710013
Xie Y, Bowe B, Mokdad AH, et al. Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016. Kidney Int. 2018;94(3):567-581. https://doi.org/10.1016/j.kint.2018.04.011 PMID:30078514
Carpio EM, Ashworth M, Asgari E, et al. Hypertension and cardiovascular risk factor management in a multi-ethnic cohort of adults with CKD: a cross sectional study in general practice. J Nephrol. 2022;35(3):901-910. https://doi.org/10.1007/s40620-021-01149-0 PMID:34782969
Cockwell P, Fisher L-A. The global burden of chronic kidney disease. Lancet. 2020;395(10225):662-664. https://doi.org/10.1016/S0140-6736(19)32977-0 PMID:32061314
Jankowski J, Floege J, Fliser D, Böhm M, Marx N. Cardiovascular disease in chronic kidney disease: pathophysiological insights and therapeutic options. Circulation. 2021;143(11):1157-1172. https://doi.org/10.1161/CIRCULATIONAHA.120.050686 PMID:33720773
Darlington O, Dickerson C, Evans M, et al. Costs and healthcare resource use associated with risk of cardiovascular morbidity in patients with chronic kidney disease: evidence from a systematic literature review. Adv Ther. 2021;38(2):994-1010. https://doi.org/10.1007/s12325-020-01607-4 PMID:33432542
Saran R, Robinson B, Abbott KC, et al. US renal data system 2019 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis. 2020;75(1)(suppl 1):A6-A7. https://doi.org/10.1053/j.ajkd.2019.09.003 PMID:31704083
Elshahat S, Cockwell P, Maxwell AP, Griffin M, O’Brien T, O’Neill C. The impact of chronic kidney disease on developed countries from a health economics perspective: A systematic scoping review. PLoS One. 2020;15(3):e0230512. https://doi.org/10.1371/journal.pone.0230512 PMID:32208435
Wyld ML, Lee CM, Zhuo X, et al. Cost to government and society of chronic kidney disease stage 1-5: a national cohort study. Intern Med J. 2015;45(7):741-747. https://doi.org/10.1111/imj.12797 PMID:25944415
Vanholder R, Annemans L, Brown E, et al; European Kidney Health Alliance. Reducing the costs of chronic kidney disease while delivering quality health care: a call to action. Nat Rev Nephrol. 2017;13(7):393-409. https://doi.org/10.1038/nrneph.2017.63 PMID:28555652
Levin A, Rigatto C, Brendan B, et al; CanPREDDICT investigators. Cohort profile: canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT). BMC Nephrol. 2013;14(1):121. https://doi.org/10.1186/1471-2369-14-121 PMID:23758910
Shlipak MG, Tummalapalli SL, Boulware LE, et al; Conference Participants. The case for early identification and intervention of chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2021;99(1):34-47. https://doi.org/10.1016/j.kint.2020.10.012 PMID:33127436
Agenzia Italiana del Farmaco. Determina 13 gennaio 2023.Regime di rimborsabilita' e prezzo a seguito di nuove indicazioni terapeutiche e riclassificazione, ai sensi dell'articolo 8, comma 10, della legge 24 dicembre 1993, n. 537, del medicinale per uso umano «Forxiga». (Determina n. 6/2023). (23A00305) (GU Serie Generale n.17 del 21-01-2023). Online https://www.gazzettaufficiale.it/eli/id/2023/01/21/23A00304/SG (Accessed September 2024)
Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446. https://doi.org/10.1056/NEJMoa2024816 PMID:32970396
McEwan P, Hafner M, Jha V, et al. Translating the efficacy of dapagliflozin in chronic kidney disease to lower healthcare resource utilization and costs: a medical care cost offset analysis. J Med Econ. 2023;26(1):1407-1416. https://doi.org/10.1080/13696998.2023.2264715 PMID:37807895
Heerspink HJL, Cherney D, Postmus D, et al; DAPA-CKD Trial Committees and Investigators. A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function. Kidney Int. 2022;101(1):174-184. https://doi.org/10.1016/j.kint.2021.09.005 PMID:34560136
Mauskopf JA, Sullivan SD, Annemans L, et al. Principles of good practice for budget impact analysis: report of the ISPOR Task Force on good research practices--budget impact analysis. Value Health. 2007;10(5):336-347. https://doi.org/10.1111/j.1524-4733.2007.00187.x PMID:17888098
Istat. Demografia in cifre. Popolazione residente per sesso, età e stato civile al 1° gennaio 2023. Online https://demo.istat.it/app/?l=it&a=2023&i=POS (Accessed September 2024)
De Nicola L, Donfrancesco C, Minutolo R, et al. [Epidemiology of chronic kidney disease in Italy: current state and contribution of the CARHES study]. Ital Nefrol. 2011;28(4):401-407. PMID:21809309
Conte G, De Nicola L, Minutolo R, Studio CARHES, 44° Congresso Nazionale di Cardiologia, Firenze 30 maggio - 1 giugno 2013. Data on file.
Conte G, Pacilio M, Garofalo C, Liberti ME, Provenzano M, Santangelo S. [Epidemiology of CKD in Italy and prevention strategies]. G Ital Nefrol. 2014;31(4):gin/31.4.11. PMID:25098466
Cupisti A, Vigo V, Baronti ME, D’Alessandro C, Ghiadoni L, Egidi MF. Vitamin D status and cholecalciferol supplementation in chronic kidney disease patients: an Italian cohort report. Int J Nephrol Renovasc Dis. 2015;8:151-157. https://doi.org/10.2147/IJNRD.S90968 PMID:26640388
Molly Murton 1, Danielle Goff-Leggett 1, Anna Bobrowska et al. Burden of Chronic Kidney Disease by KDIGO Categories of Glomerular Filtration Rate and Albuminuria: A Systematic Review. Adv Ther 2021 Jan; 38 (1): 180-200. https://doi.org/10.1007/s12325-020-01568-8 PMID: 33231861
Jommi C, Armeni P, Battista M, et al; IRIDE Study Group. The Cost of Patients with Chronic Kidney Failure Before Dialysis: Results from the IRIDE Observational Study. PharmacoEconom Open. 2018;2(4):459-467. https://doi.org/10.1007/s41669-017-0062-z PMID:29623638
Istat. Rivaluta. Rivalutazioni e documentazione su prezzi, costi e retribuzioni contrattuali. Online https://rivaluta.istat.it/ (Accessed September 2024)
Vaccaro CM, Sopranzi F. A comparison between the costs of dialysis treatments in Marche Region, Italy: Macerata and Tolentino hospitals. Ann Ist Super Sanità 2017 | Vol. 53, No. 4: 344-349. Online https://www.iss.it/documents/20126/45616/ANN_17_04_12.pdf (Accessed September 2024)
Ministero della Salute. Tariffe massime di riferimento per la remunerazione delle prestazioni di assistenza specialistica ambulatoriale e di assistenza protesica. Online https://www.quotidianosanita.it/allegati/allegato1730970975.pdf (Accessed September 2024)
Società Italiana Nefrologia. Registro Italiano di Dialisi e Trapianto (RIDT) Report Anno 2021. Online https://ridt.sinitaly.org/ (Accessed September 2024)
Gazzetta Ufficiale della Repubblica Italiana. Remunerazione delle prestazioni di assistenza ospedaliera per acuti, assistenza ospedaliera di riabilitazione e di lungodegenza post acuzie e di assistenza specialistica ambulatoriale. Supplemento ordinario alla “Gazzetta Ufficiale” n. 23 del 28 gennaio 2013 - Serie generale. https://www.gazzettaufficiale.it/atto/serie_generale/caricaDettaglioAtto/originario?atto.dataPubblicazioneGazzetta=2013-01-28&atto.codiceRedazionale=13A00528&elenco30giorni=false (Accessed September 2024)
Roggeri DP, Roggeri A, Zocchetti C, Cozzolino M, Rossi C, Conte F. Real-world data on healthcare resource consumption and costs before and after kidney transplantation. Clin Transplant. 2019;33(10):e13728. https://doi.org/10.1111/ctr.13728 PMID:31587354
Maggioni AP, Orso F, Calabria S, et al; ARNO Observatory. The real-world evidence of heart failure: findings from 41 413 patients of the ARNO database. Eur J Heart Fail. 2016;18(4):402-410. https://doi.org/10.1002/ejhf.471 PMID:26754527
Nagib SN, Abdelwahab S, Amin GEE, Allam MF. Screening and early detection of chronic kidney disease at primary healthcare. Clin Exp Hypertens. 2021;43(5):416-418. https://doi.org/10.1080/10641963.2021.1896726 PMID:33726610
Tangri N, Chadban S, Cabrera C, Retat L, Sánchez JJG. Projecting the Epidemiological and Economic Impact of Chronic Kidney Disease Using Patient-Level Microsimulation Modelling: Rationale and Methods of Inside CKD. Adv Ther. 2023;40(1):265-281. https://doi.org/10.1007/s12325-022-02353-5 PMID:36307575
Dwyer JP, Agiro A, Desai P, Cremisi H. Short-term costs in patients with chronic kidney disease treated with dapagliflozin: a retrospective cohort study. Expert Rev Pharmacoecon Outcomes Res. 2023;23(9):1057-1066. https://doi.org/10.1080/14737167.2023.2237679 PMID:37540162
de Pouvourville G, Rossignol P, Boussahoua M, et al. Budget impact analysis of expanding gliflozin coverage in the CKD population: a french perspective. Adv Ther. 2023;40(9):3751-3769. https://doi.org/10.1007/s12325-023-02574-2 PMID:37341914
Alnsasra H, Tsaban G, Solomon A, et al. Dapagliflozin versus empagliflozin in patients with chronic kidney disease. Front Pharmacol. 2023;14:1227199. https://doi.org/10.3389/fphar.2023.1227199 PMID:37601066
Vart P, Jongs N, Wheeler DC, Heerspink HJL, Langkilde AM, Chertow GM. Effectiveness and safety of dapagliflozin for black vs white patients with chronic kidney disease in North and South america: a secondary analysis of a randomized clinical trial. JAMA Netw Open. 2023;6(4):e2310877. https://doi.org/10.1001/jamanetworkopen.2023.10877 PMID:37103935
Vart P, Correa-Rotter R, Hou FF, et al. Efficacy and safety of dapagliflozin in patients with CKD across major geographic regions. Kidney Int Rep. 2022;7(4):699-707. https://doi.org/10.1016/j.ekir.2022.01.1060 PMID:35497805
Piccinni C, Dondi L, Calabria S, et al. Chronic Kidney Disease Eligible for SGLT2 Inhibitors Through the Integration of Italian Administrative and Primary Care Data. G Ital Nefrol. 2024;41(3):2024-vol3. https://doi.org/10.69097/41-03-2024-08 PMID:38943329
Scheen AJ. An update on the safety of SGLT2 inhibitors. Expert Opin Drug Saf. 2019;18(4):295-311. https://doi.org/10.1080/14740338.2019.1602116 PMID:30933547
Turchetti G, Bellelli S, Amato M, et al; On Behalf of the Tuscany CKD Study Group. The social cost of chronic kidney disease in Italy. Eur J Health Econ. 2017;18(7):847-858. https://doi.org/10.1007/s10198-016-0830-1 PMID:27699568
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2024 The authors
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Accepted 2024-11-11
Published 2024-12-02
