title: A cost-utility analysis of prolonged-release tacrolimus relative to immediate-release tacrolimus and ciclosporin in liver transplant recipients in the UK.
abstract: BACKGROUND
  Calcineurin inhibitors (CNIs) represent the cornerstone of immunosuppressive therapy after liver transplantation. A recent network meta-analysis (NMA) evaluated the relative efficacy of CNIs ciclosporin, prolonged-release (PR) tacrolimus, and immediate-release (IR) tacrolimus in adult liver transplant recipients based on randomized and large observational trials published since 2000. Based on the NMA findings, the present study evaluated the cost-utility of PR tacrolimus relative to ciclosporin or IR tacrolimus in liver transplant recipients in the UK.
  
  
  METHODS
  A Markov model was developed to evaluate the cost-utility of immunosuppressive regimens in liver transplant recipients, capturing costs associated with immunosuppression, retransplantation, acute rejection (AR), and cytomegalovirus infection. Mortality, graft loss, and AR odds ratios were derived from the NMA. Costs were taken from the British National Formulary and the NHS National Tariff and expressed in 2016 pounds sterling. Future costs and effects were discounted at 3.5% annually.
  
  
  RESULTS
  Over 25 years, PR tacrolimus resulted in increased life expectancy and quality-adjusted life expectancy (QALE) relative to IR tacrolimus and ciclosporin. Relative to ciclosporin, QALE increased by 1.17 quality-adjusted life years (QALYs) with PR tacrolimus while costs increased by GBP £4645, yielding an incremental cost-effectiveness ratio (ICER) of £3962 per QALY gained. Relative to IR tacrolimus, QALE increased by 0.78 QALYs and costs by £1474, resulting in an ICER of £1889 per QALY gained. Sensitivity analysis showed the analysis to be most sensitive to dosing assumptions.
  
  
  CONCLUSIONS
  Based on a UK-specific analysis of the projected cost-utility of PR tacrolimus relative to IR tacrolimus and ciclosporin, PR tacrolimus was cost-effective, improving life expectancy and QALE relative to both IR tacrolimus and ciclosporin, yielding ICERs below £20 000 per QALY gained. The main limitations of the study were data source heterogeneity and omitting the economic and clinical effects of treating aspects of recurrent liver disease.
authors.affiliation: a Astellas Pharma Europe Limited , Chertsey , UK ;
authors.forename: Gorden
authors.initials: G
authors.lastname: Muduma
authors.affiliation: a Astellas Pharma Europe Limited , Chertsey , UK ;
authors.forename: Isaac
authors.initials: I
authors.lastname: Odeyemi
authors.affiliation: b Ossian Health Economics and Communications , Basel , Switzerland.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Pollock
mesh_terms: D003362:Cost-Benefit Analysis; D016572:Cyclosporine / Q000191:economics* / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000191:economics*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000191:economics* / Q000627:therapeutic use*; D016031:Liver Transplantation; D018803:Models, Economic; D019057:Quality-Adjusted Life Years; D013222:State Medicine; D016559:Tacrolimus / Q000008:administration & dosage* / Q000191:economics*
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus
keywords: Cost-utility; Great Britain; ciclosporin; liver transplantation; tacrolimus