title: Evaluating the economic implications of non-adherence and antibody-mediated rejection in renal transplant recipients: the role of once-daily tacrolimus in the UK.
abstract: OBJECTIVE
  While short-term kidney graft survival has gradually improved over time, improvements in long-term graft survival have been more modest. One key clinical factor limiting improved longer-term outcomes is antibody-mediated rejection (AbMR), the incidence of which appears to be higher in patients who are non-adherent to immunosuppressants. Recent data show that adherence can be improved by reducing pill burden. The aim of the present study was to model the incidence and economic consequences of graft loss and AbMR in patients taking once- vs twice-daily tacrolimus in the UK.
  
  
  METHODS
  A combined decision tree and Markov model was developed to estimate the incidence of graft failure, AbMR and mortality in renal transplant recipients taking once- vs twice-daily tacrolimus. Underlying rates of graft failure and mortality were derived from UK-specific sources. Proportions of patients adherent to once- vs twice-daily tacrolimus were taken from a recent randomized clinical trial and relative risks of graft failure and AbMR were taken from a prospective, multi-center analysis of 315 patients. Cost data were taken from the British National Formulary and National Health Service reference costs and reported in 2014 pounds sterling.
  
  
  RESULTS
  Modeling results showed that improved adherence would be associated with reduced incidence of AbMR and graft failure in renal transplant recipients. Based on improvements in adherence resulting from switching from twice-daily to once-daily tacrolimus, the modeling analysis projected cost savings of GBP 4862 per patient over 5 years with Advagraf relative to Prograf, on absolute costs of GBP 40,974 and GBP 45,836, respectively.
  
  
  CONCLUSIONS
  Using Advagraf in place of Prograf in renal transplant recipients was predicted to be associated with lower pharmacy, dialysis and AbMR treatment costs, with the reduction in AbMR and dialysis costs being driven by improved adherence to the Advagraf regimen and consequent reductions in graft failure and onset of AbMR.
authors.affiliation: a a Astellas Pharma EMEA Limited , Chertsey , UK.
authors.forename: G
authors.initials: G
authors.lastname: Muduma
authors.affiliation: a a Astellas Pharma EMEA Limited , Chertsey , UK.
authors.forename: I
authors.initials: I
authors.lastname: Odeyemi
authors.affiliation: b b Ossian Health Economics and Communications , Basel , Switzerland.
authors.forename: R F
authors.initials: RF
authors.lastname: Pollock
mesh_terms: D003365:Costs and Cost Analysis; D003663:Decision Trees; D006084:Graft Rejection / Q000191:economics / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects / Q000191:economics*; D008390:Markov Chains; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012189:Retrospective Studies; D018570:Risk Assessment; D016559:Tacrolimus / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D006113:United Kingdom / Q000453:epidemiology; D016903:Drug Monitoring
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: Costs and cost analysis; Graft rejection; Great Britain; Tacrolimus