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.

Keywords:

• Cost-utility
• liver transplantation
• tacrolimus
• ciclosporin
• Great Britain

Transparency

Declaration of funding

This study was supported by funding from Astellas Pharma Europe Limited.

Declaration of financial/other relationships

RFP is a full-time employee of Ossian Health Economics and Communications GmbH, which received consultancy fees from Astellas Pharma Europe Limited to conduct the analysis and prepare the manuscript. GM and IO are full-time employees of Astellas Pharma Euope Limited, which manufactures immediate-release and prolonged-release tacrolimus. Astellas Pharma Euope Limited is providing the funding for the article processing charge. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

RFP developed the cost-utility model, ran the analyses, and drafted the manuscript. GM formulated the research question, reviewed the model, and provided critical revisions to the manuscript. IO reviewed and provided critical revisions to the manuscript.