Skip to main content
SpringerLink
Log in

Evaluation of the cost effectiveness of sirolimus versus tacrolimus for immunosuppression following renal transplantation in the UK

  • Original Research Article
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

Introduction: Immunosuppressive therapy is required to prevent graft rejection. Calcineurin inhibitors such as tacrolimus are paradoxically toxic to the kidney, whereas sirolimus (rapamycin; Rapamune®) is not generally associated with the nephrotoxicity of CNIs. The purpose of this study was to evaluate the relative cost utility of sirolimus versus tacrolimus for the primary prevention of graft rejection in renal transplant recipients in the UK.

Methods: A stochastic simulation model was constructed using clinical trial and observational data comparing the two treatments. Time duration was up to 20 years. Costs were from a UK NHS perspective, valued at 2003 prices and discounted at 6%. Benefits were discounted at 1.5%. Simulated events included patient and graft survival, haemodialysis, peritoneal dialysis, re-transplants and acute rejection. Costs were summed for events and various maintenance therapies. Utility was differentially accredited depending upon survival and using the alternative renal replacement therapies. Outcome was predicted using post-transplant creatinine levels up to 3 years. Extensive statistical economic and sensitivity analyses were undertaken.

Results: Over the 10-year horizon, sirolimus gained 0.72 years (discounted) of functioning graft over tacrolimus, resulting in an incremental cost per year of functioning graft that was dominant. Over a 20-year time horizon, the cost effectiveness of sirolimus over tacrolimus further improved with an average discounted gain in years of a functioning graft of 1.8 years, resulting in an incremental cost-utility ratio that was also dominant. The number of haemodialysis events was 48 243 for sirolimus recipients versus 127 829 for those receiving tacrolimus and peritoneal dialysis events 40 872 versus 105 249, respectively. Similar values were obtained when real-life observational data on tacrolimus use in Cardiff, Wales were entered into the model. Using data from Cardiff, sirolimus remained dominant over tacrolimus under all scenarios.

Conclusion: Our study suggests that sirolimus may be more cost effective than tacrolimus for the primary prevention of graft rejection in renal transplant recipients in the UK. Sirolimus was economically ‘dominant’ under almost all scenarios investigated. This finding was robust using statistical economic analysis and univariate sensitivity analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Fig. 2
Table II
Table III
Table IV
Fig. 3
Table V
Fig. 4
Table VI

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Irish W, Sherrill B, Brennan DC, et al. Three-year post transplant graft survival in renal-transplant patients with graft function at 6 months receiving tacrolimus or cyclosporine microemulsion within a triple-drug regimen. Transplantation 2003; 76: 1686–90

    Article  PubMed  CAS  Google Scholar 

  2. Johnson C, Ahsan N, Gonwa T, et al. Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation. Transplantation 2000; 69: 834–41

    Article  PubMed  CAS  Google Scholar 

  3. Kaplan B, Schold JD, Meier-Kriesche HU. Long-term graft survival with neoral and tacrolimus: a paired kidney analysis. J Am Soc Nephrol 2003; 14: 2980–4

    Article  PubMed  CAS  Google Scholar 

  4. Gonwa T, Johnson C, Ahsan N, et al. Randomized trial of tacrolimus + mycophenolate mofetil or azathioprine versus cyclosporine + mycophenolate mofetil after cadaveric kidney transplantation: results at three years. Transplantation 2003; 75: 2048–53

    Article  PubMed  CAS  Google Scholar 

  5. Jurewicz WA. Tacrolimus versus cyclosporin immunosuppression: long-term outcome in renal transplantation. Nephrol Dial Transplant 2003; 18 Suppl. 1: i7–11

    Article  PubMed  Google Scholar 

  6. Bunnapradist S, Daswani A, Takemoto SK. Graft survival following living-donor renal transplantation: a comparison of tacrolimus and cyclosporine microemulsion with mycophenolate mofetil and steroids. Transplantation 2003; 76: 10–5

    Article  PubMed  CAS  Google Scholar 

  7. Henry ML. Cyclosporine and tacrolimus (FK506: a comparison of efficacy and safety profiles. Clin Transplant 1999; 13: 209–20

    Article  PubMed  CAS  Google Scholar 

  8. Podbielski J, Schoenberg L. Use of sirolimus in kidney transplantation. Prog Transplant 2001; 11: 29–32

    PubMed  CAS  Google Scholar 

  9. Morelon E, Mamzer-Bruneel MF, Peraldi MN, et al. Sirolimus: a new promising immunosuppressive drug: towards a rationale for its use in renal transplantation. Nephrol Dial Transplant 2001; 16: 18–20

    Article  PubMed  CAS  Google Scholar 

  10. National Institute for Health and Clinical Excellence. NICE guidelines on renal transplant immunosuppression [online]. Available from URL: http://www.nice.org.uk/ page.aspx?.o=221103 [Accessed 2005 Jun 15]

  11. National Kidney Federation. Transplantation and live donors [online]. Available from URL: http://www.kidney.org.uk/ campaigns/Transplantation/ukt-press-dec03.htm1 [Accessed 2005 Oct 27]

  12. Buxton MJ, Drummond MF, Van Hour BA, et al. Modelling in economic evaluation: an unavoidable fact of life. Health Econ 1997; 6: 217–27

    Article  PubMed  CAS  Google Scholar 

  13. Kamon J. Alternative decision modelling techniques for the evaluation of health care technologies: markov processes versus discrete event simulation. Health Econ 2003; 12: 837–48

    Article  Google Scholar 

  14. Gentil MA, Cantarell Aixendri C, Gonzalez Roncero FM, et al. Impact of the new drugs in the cost of maintenance immunosuppression of renal transplantation: is it justified? Nephrol Dial Transplant 2004; 19 Suppl. 3: III77–82

    Article  PubMed  Google Scholar 

  15. Gonzalez Molina M, Sola E, Cabello M, et al. Effect of the immunosuppressive treatment on long-term renal graft survival. Nephrol Dial Transplant 2004; 19 Suppl. 3: III52–56

    Article  PubMed  Google Scholar 

  16. Douglas R. Department of Health (UK). Discount rates and the cost of capital -EL (97) 71 [online]. Available from URL: http://www.dh.gov.uk//assetRoot/04/01/13/61/04011361.pdf [Accessed 2005 Jun 18]

  17. West RR, McNabb R, Thompson AG, et al. Estimating implied rates of discounting in health care decision making. Health Technol Assess 2003; 7: 1–60

    PubMed  CAS  Google Scholar 

  18. McEwan P, Keshwar B, Dixon S, et al. Patterns of graft and patient survival following renal transplantation and evaluation of serum creatinine as a predictor of survival: a review of data collected from one clinical centre over 34 years. Curr Med Res Opin 2005; 21 (11): 1793–1800

    Article  PubMed  Google Scholar 

  19. Oberbauer R, Kreis H, Johnson RW, et al. Rapamune Maintenance Regimen Study Group. Long-term improvement in renal function with sirolimus after early cyclosporine withdrawal in renal transplant recipients: 2-year results of the Rapamune Maintenance Regimen Study. Transplantation 2003; 76: 364–70

    Article  PubMed  CAS  Google Scholar 

  20. Rogers J, Ashcraft EE, Emovon OE, et al. Long-term outcome of sirolimus rescue in kidney-pancreas transplantation. Transplantation 2004; 78: 619–22

    Article  PubMed  CAS  Google Scholar 

  21. Kiberd BA. Should hepatitis C-infected kidneys be transplanted in the United States? Transplantation 1994; 57: 1068–72

    PubMed  CAS  Google Scholar 

  22. Laupacis A, Keown P, Pus N, et al. A study of the quality of life and cost utility of renal transplantation. Kidney Int 1996; 50: 235–42

    Article  PubMed  CAS  Google Scholar 

  23. Gudex CM. Health-related quality of life in end-stage renal failure. Qual Life Res 1995; 4: 359–66

    Article  PubMed  CAS  Google Scholar 

  24. Department of Health. NHS costing manual: detailed guide to costing for NHS providers and commissioners [online]. Available from URL: http://www.dh.gov.uk/PolicyAndGuidance/ OrganisationPolicy/FinanceAndPlanning/NHSCostingManual /fs/en [Accessed 2004 May 1]

  25. British National Formulary [online]. Available from URL: www.bnf.org. [Accessed 2004 May 1]

  26. Parlevliet KJ, ten Berge RJ, Raasveld MH, et al. Low-dose OKT3 induction therapy following renal transplantation: a controlled study. Nephrol Dial Transplant 1994; 9: 698–703

    PubMed  CAS  Google Scholar 

  27. Hariharan S, McBride MA, Cherikh WS, et al. Post-transplant renal function in the first year predicts long-term kidney transplant survival. Kidney Int 2002; 62: 311–8

    Article  PubMed  Google Scholar 

  28. Friedman PJ. Serum creatinine: an independent predictor of survival after stroke. J Intern Med 1991; 229: 175–9

    Article  PubMed  CAS  Google Scholar 

  29. Ferrara JJ, Wanamaker S, Carey LC. Preoperative serum creatinine as a predictor of survival in perforated gastroduodenal ulcer. Am Surg 1985; 51: 551–5

    PubMed  CAS  Google Scholar 

  30. Carter JT, Lee CM, Weinstein RJ, et al. Evaluation of the older cadaveric kidney donor: the impact of donor hypertension and creatinine clearance on graft performance and survival. Transplantation 2000; 70: 765–71

    Article  PubMed  CAS  Google Scholar 

  31. Cecka JM. Outcome statistics of renal transplants with an emphasis on long-term survival. Clin Transplant 1994; 8: 324–7

    PubMed  CAS  Google Scholar 

  32. Flechner SM, Modlin CS, Serrano DP, et al. Determinants of chronic renal allograft rejection in cyclosporine-treated recipients. Transplantation 1996; 62: 1235–41

    Article  PubMed  CAS  Google Scholar 

  33. Zuckermann A, Plotter M, Czemy M, et al. Even slightly impaired kidney function (creatinine >1.79 MMOL/L) one year after cardiac transplantation has a negative impact on long term survival. J Heart Lung Transplant 2001; 20: 206

    Article  PubMed  Google Scholar 

  34. Laskow DA, Neylan JF, Shapiro RS, et al. The role of tacrolimus in adult kidney transplantation: a review. Clin Transplant 1998; 12: 489–503

    PubMed  CAS  Google Scholar 

  35. Gordois A, Mudge M, Davey P, et al. The cost-effectiveness of sirolimus with cyclosporin withdrawal versus low dose sirolimus and continued cyclosporin when initiated within four months of renal transplantation [abstract]. Value Health 2004; 7: 364

    Article  Google Scholar 

Download references

Acknowledgements

This study was funded by Wyeth UK, the manufacturer of sirolimus. Pete Conway is a salaried employee of Wyeth UK. The authors declare that they have no other conflict of interest.

Phil McEwan developed the simulation model and undertook much of the analysis.

Simon Dixon designed the study and co-wrote first draft.

Keshwar Baboolal provided clinical input for the study.

Pete Conway commissioned and co-designed the study and commented on various drafts.

Craig Currie designed the study, had overall responsibility for the study, and wrote the first draft and subsequent redrafts.

Author information

Authors and Affiliations

  1. School of Mathematics, Cardiff University, Cardiff, Wales, UK

    Phil McEwan

  2. School of Health and Related Research, University of Sheffield, Sheffield, England, UK

    Simon Dixon

  3. Department of Renal Medicine, University Hospital of Wales, Cardiff, Wales, UK

    Keshwar Baboolal

  4. Health Economics, Wyeth Laboratories-UK, Maidenhead, England, UK

    Pete Conway

  5. Department of Medicine, University of Wales College of Medicine, Cardiff, Wales, UK

    Craig J. Currie

Authors
  1. Phil McEwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simon Dixon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keshwar Baboolal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pete Conway
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Craig J. Currie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Phil McEwan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McEwan, P., Dixon, S., Baboolal, K. et al. Evaluation of the cost effectiveness of sirolimus versus tacrolimus for immunosuppression following renal transplantation in the UK. Pharmacoeconomics 24, 67–79 (2006). https://doi.org/10.2165/00019053-200624010-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00019053-200624010-00006

Keywords

Search

Navigation