Economic evaluations of calcineurin inhibitors in renal transplantation

Miners, A. H., Yao, G., Raftery, J. and Taylor, R. S. (2007) Economic evaluations of calcineurin inhibitors in renal transplantation. PharmacoEconomics, 25(11), pp. 935-947. (doi: 10.2165/00019053-200725110-00004) (PMID:17960952)

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Abstract

People receiving a renal transplant require long-term treatment with immunosuppressant drugs. Contemporary regimens usually include a calcineurin inhibitor (CI), either ciclosporin or tacrolimus, in conjunction with at least one other drug. The aim of this study was to review the economic literature relating to the choice of CIs in patients following renal transplantation, with the specific intention of highlighting the challenges in estimating their cost effectiveness. A systematic literature search and narrative analysis was carried out, and 12 studies of varying quality and complexity were reviewed. All of the studies compared ciclosporin, azathioprine and a corticosteroid (CAS) with tacrolimus, azathioprine and a corticosteroid (TAS) but only three also evaluated the costs and effects of other possible treatment regimens. A variety of different evaluative frameworks were employed, from single randomised controlled trial-based studies over relatively short-time periods (6 months) to more complex Bayesian modelling techniques. The studies were broadly consistent in concluding that TAS was more effective than CAS in terms of reducing the rate of acute rejection episodes. Of the studies that undertook decision modelling, all but one estimated that TAS was associated with better graft-related outcomes such as rejection-free life-years, patient-survival and QALYs. Six of the studies concluded that the healthcare costs associated with TAS were lower than those for CAS. A seventh study suggested that TAS was the least costly option if costs were considered over a relatively long time period (14 years). Only one study clearly concluded that CAS was more cost effective than TAS. Clinical evidence clearly shows that TAS is more effective than CAS in terms of reducing the incidence of acute rejection following renal transplantation. The majority of published economic evaluations suggest that TAS is also the more cost-effective option. However, the economic evaluations contained a number of methodological limitations, undermining the confidence that can be attached to their results. Future economic evaluations of the CIs, and immunosuppressants in general, should address these issues in order to produce more robust cost-effectiveness estimates. Most importantly, they should evaluate a wider range of potential treatment options. Renal transplantation has become the treatment of choice for most patients with end-stage renal failure, as the only alternative is life-long haemodialysis.[1] However, transplantation is only possible because of the existence of immunosuppressant drug therapy.[2] The worldwide number of people who have received renal transplants is unknown, but in 2005 approximately 1800 people in England and Wales underwent renal transplantation.[3] In 2004, in Australia and New Zealand, approximately 350 people received transplants[4] and 14 000 people in the US underwent transplantation in the previous year.[5] Predictions also suggest that the annual prevalence of people with transplants is likely to increase by 4–5% annually as the population ages.[6] Treatment with immunosuppressants is lifelong, or at least long-term, with the aim of prolonging patient and graft survival without exposing the patient to risks of excessive immunosuppression or nephrotoxicity.[2] There is no standard treatment regimen for patients who have undergone renal transplantation.[7] However, most treatment centres attempt to categorise donor-recipient pairs according to the degree of perceived immunological risk, and offer corresponding differing intensities of immunosuppression.[7] They also tend to adopt different strategies for patients with delayed graft function, for those who receive kidneys from non-heart-beating donors and for those who receive kidneys from live donors. The choice of treatment regimen is also influenced by the adverse-effect profiles of the specific drugs.[7] The immunosuppressives are associated with a number of adverse effects, but nephrotoxicity is a particular complication of some, notably the calcineurin inhibitors (CIs), and is thought to increase the risk of chronic graft dysfunction.[2] Presently in the UK alone, there are approximately 30 000 patients receiving drug treatment following kidney transplantation. Assuming that the yearly cost of drug treatment is £3000,[8] this equates to an annual cost of approximately £90 million per annum (2006 value). Treatment with immunosuppressive drugs can be considered in three stages: induction, initial and maintenance therapy. Induction therapy is a course of intensive immunosuppression for about 2 weeks immediately pre- or post-operatively. The aim is to ‘switch off’ the immune system after transplantation to reduce the likelihood of accelerated and acute rejection. Initial therapy is the treatment given to recipients between months 0–3 after transplantation.[9] Initial therapy has traditionally constituted ‘triple therapy’, in which a CI (traditionally ciclosporin) is used in combination with a corticosteroid (prednisolone) and azathioprine. Maintenance therapy is the treatment that transplant recipients receive in the long-term, throughout the duration of allograft survival. Maintenance therapy is often identical to initial therapy, except that the drug dosage may be reduced. Two CIs are currently available: ciclosporin and tacrolimus. Ciclosporin was originally available as an oily solution (Sandimmun®Footnote 1) but is now only marketed as an oral solution/microemulsion (Neoral®); the pharmacokinetic profiles of the two agents are believed to be different. Tacrolimus (Prograf®) is not chemically related to ciclosporin but is considered to have a similar mode of action. The precise marketing authorisation for tacrolimus varies by country, but broadly speaking it is licensed for primary immunosuppression in kidney allograft recipients. In most countries, including Japan, UK, New Zealand and Australia, it is also licensed for kidney allograft rejection resistant to conventional immunosuppressive regimens.[10] The demand for healthcare resources is finite, meaning that decisions need to be made to determine those treatments that should be funded and those that should not. A recent systematic review of the randomised controlled trial (RCT) evidence suggested that tacrolimus, azathioprine and a corticosteroid (TAS) is more effective than ciclosporin, azathioprine and a corticosteroid (CAS) in terms of reducing the rate of acute rejection episodes following renal transplantation. The aim of this study was to review the associated economic evidence to determine the most cost-effective treatment option and to highlight areas of methodological concern.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Taylor, Professor Rod
Authors: Miners, A. H., Yao, G., Raftery, J., and Taylor, R. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > MRC/CSO SPHSU
Journal Name:PharmacoEconomics
Publisher:Springer
ISSN:1170-7690
ISSN (Online):1179-2027

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