title: Evaluation of the cost effectiveness of sirolimus versus tacrolimus for immunosuppression following renal transplantation in the UK.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Mathematics, Cardiff University, Cardiff, Wales, UK. mcewan@cardiff.ac.uk
authors.forename: Phil
authors.initials: P
authors.lastname: McEwan
authors.forename: Simon
authors.initials: S
authors.lastname: Dixon
authors.forename: Keshwar
authors.initials: K
authors.lastname: Baboolal
authors.forename: Pete
authors.initials: P
authors.lastname: Conway
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Currie
mesh_terms: D000328:Adult; D003362:Cost-Benefit Analysis; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000191:economics* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D020123:Sirolimus / Q000191:economics* / Q000627:therapeutic use; D016559:Tacrolimus / Q000191:economics* / Q000627:therapeutic use; D006113:United Kingdom
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus