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Background: Monitoring of microemulsion ciclosporin (cyclosporine; Neoral) by 2-hour post-dose drug concentrations (C2) is an accurate measure of ciclosporin absorption efficiency and exposure, and appears superior to trough (C0) monitoring for prediction of rejection risk. A predictive decision model was used to determine if this approach also reduces total treatment costs in the first 12 months after renal transplantation., Methods: Parameter estimates for key clinical events were derived from the literature and from prospective pharmacokinetic studies comprising 234 adult HLA-non-identical renal graft recipients at seven Canadian centres. Patients were treated with microemulsion ciclosporin (Neoral), corticosteroids and azathioprine or mycophenolate mofetil. Using the perspective of the Canadian healthcare provider, total treatment costs for the C2 versus the C0 strategy were modelled over 12 months, and then remodelled using conservative estimates to extend the timeframe to 5 years. Health resources were valued in 1999 Canadian dollars., Results: The incidence of acute rejection was estimated to be 25% at 1 year in patients monitored by C0 and 18% in those monitored by C2. Patient survival was considered to be independent of monitoring strategy, and graft loss was predicted to be 1.4% lower in the C2 group. The studies suggested no important differences in comorbidity and the costs of C0 and C2 monitoring and ambulatory-based adverse events were held equivalent. Using these inputs, the average cost per patient for the first year post-transplant was Can dollars 46,857 for C0 monitoring and Can dollars 45,306 for C2 monitoring, rising to Can dollars 146,879 and Can dollars 142,569 after 5 years. The predicted cost for initial hospitalisation was Can dollars 11,280 for C0 and Can dollars 10,806 for C2 monitoring. The cost of maintenance immunosuppressive drug use, graft loss and dialysis was Can dollars 19,098 in the C0 group and Can dollars 18,612 in the C2 group, while acute rejection treatment costs were Can dollars 2169 and Can dollars 1577, respectively. An additional Can dollars 14,310 was consumed by other events, including repeat hospitalisation, for each group. Sensitivity analysis indicated that the most influential parameters affecting savings due to C2 monitoring were a reduction in the duration of initial and follow-up hospitalisations and reduced risks of acute rejection and subsequent graft loss., Conclusions: Compared with traditional trough concentration monitoring, ciclosporin monitoring at 2 hours post-dose produced a predicted saving of Can dollars 1551 during the first year after renal transplant. Although modelling assumptions become more restrictive over time, this projection allows a preliminary assessment of the long-term economic impact of the routine use of C2 monitoring.

Background: The economic impact of therapeutic non-adherence in chronic diseases has rarely been examined using qualitative standards for economic evaluation. This study illustrates the impact of non-adherence on the cost utility of renal transplantation versus haemodialysis from the societal perspective and examines the scope for adherence-enhancing interventions., Methods: Long-term costs and outcomes in adherent and non-adherent renal transplant patients were simulated in a Markov model. The cost (euros, year 2000 values) and outcome data that were imputed in the model were derived from a prospective study in renal transplantation candidates performed in 2002. Probabilities of adverse events, graft rejection, graft loss and death in adherent and non-adherent renal transplant patients were derived from literature., Results: Compared with dialysis, renal transplantation offers a better outcome in both adherent and non-adherent patients. Lifetime costs after transplantation in the adherent patient group are higher than lifetime dialysis costs and lifetime costs in the non-adherent patient group, mainly because adherent patients live longer after transplantation. Long-term outcomes after transplantation are better for adherent than for non-adherent patients. The mean cost per QALY gained in adherent patients relative to non-adherent patients was euro 35 021 per QALY (95% CI 26 959, 46 620)., Conclusion: Compared with established healthcare interventions, such as haemodialysis, renal transplantation can be considered a cost-effective therapy for patients with end-stage renal disease, even if patients are non-adherent after transplantation. The low incremental cost per QALY calculated in this model for adherent renal transplant patients, suggests there may be scope for adherence-enhancing interventions (provided that such interventions with a sufficiently high effectiveness exist or can be developed). As the findings are based on simulated long-term costs and outcomes, they should not be considered as precise estimates of the impact of non-adherence. This study is rather meant as an illustration of how non-adherence may impact on the results of cost-effectiveness analyses.

Objective: To compare resource use and costs in renal transplant recipients treated with basiliximab or placebo plus triple immunosuppressive therapy., Design: International randomised, double-blind, placebo-controlled trial; economic evaluation undertaken alongside the efficacy trial. The economic evaluation was performed from a UK National Health Service hospital perspective., Setting: 31 centres in 12 countries., Participants: 345 renal transplant recipients were enrolled; 340 were randomised (basiliximab 168; placebo 172) and included in the intention-to-treat analysis., Intervention: Treatment with placebo or basiliximab (20mg intravenous bolus) on day 0 and day 4 after transplantation., Main Outcome Measures: Resource utilisation in multiple categories and treatment costs for basiliximab and placebo-treated patients during the 6-month post-transplantation period., Results: No statistically significant differences were found in any of the economically important categories of resource use or in the mean cost of treatment per person across the whole trial. The mean cost of treatment, including the cost of basiliximab, was pound 16 095 for basiliximab recipients and pound 15 864 (1997/1998 costs) for placebo recipients, a mean difference of pound 231 (95% CI: - pound 1983 to pound 2446), which was not significant. Basiliximab treatment led to a significant reduction in acute rejection episodes (basiliximab 20.8%; placebo 34.9%; p = 0.005)., Conclusions: Basiliximab therapy confers a significant clinical benefit to renal transplant recipients without increasing overall treatment costs.

Background: International phase III studies (CHIB 201 and 352) showed that basiliximab, a high affinity chimeric monoclonal antibody interleukin-2 receptor antagonist, is highly effective in preventing acute rejection when used as immunoprophylaxis in patients receiving cyclosporin (Neoral). We conducted a cost evaluation by applying international clinical results to standard Japanese medical practice., Objective: To evaluate the impact of basiliximab in renal transplant patients receiving conventional immunosuppressive therapy using cyclosporin and corticosteroids from the perspective of the healthcare payer in Japan., Study Design: A decision tree model was developed, comprising seven pathways with key clinical events identified after the transplantation. The average first-year treatment costs after transplantation for patients treated with and without basiliximab were calculated using the model. A sensitivity analysis was done to measure the degree of influence of several criteria including the incidences of rejection, and rejection responding to steroid pulse therapy and antibody therapy., Methods: Estimates of key clinical events were derived from the international studies. Calculation of direct medical costs were made from the payers' perspective, based on the Social Insurance Medical Fee Table in Japan. The cost of basiliximab was assumed as zero., Main Outcome Measures and Results: Basiliximab use produced an estimated saving of 315,807 yen (2000 values) during the first year after transplantation. Reduced acute rejection treatment and dialysis most influenced the cost saving. The sensitivity analysis showed that the average cost for a patient was lower in the basiliximab group and that the model was effective within the plausible range of each criterion that would reflect renal transplantation in Japan., Conclusions: If the cost of basiliximab is less than 315,807 yen, the clinical and economic benefits of basiliximab in the first year after transplantation support the routine use of basiliximab in renal transplantation in Japan.

Mycophenolate mofetil (MMF) is an immunosuppressive drug designed to inhibit inosine monophosphate dehydrogenase (IMPDH). IMPDH is a key enzyme in the de novo purine synthesis of lymphocytes. It is crucially important for proliferative responses of human T and B lymphocytes. The inhibition of IMPDH thus leads to selective lymphocyte suppression. After successful use in various in vitro and animal models, MMF was brought to clinical trial in patients undergoing transplantation. The drug is rapidly and completely absorbed following oral administration. Pilot studies of administration with cyclosporin and corticosteroids suggested a significant reduction in the incidence of organ rejection at dosages of 1 to 3 g/day. As a result of these studies, 3 pivotal randomised double-blind multicentre trials, involving nearly 1500 patients, were designed to investigate the effects of addition of MMF to different standard immunosuppressive protocols on the prevention of acute renal allograft rejection. After 6 months, the rates of biopsy-proven rejection were significantly reduced in patients receiving MMF. In combination with cyclosporin and corticosteroids, the adverse effect profile resembled that of azathioprine. Most adverse effects were associated with the gastrointestinal tract, the blood system and opportunistic infections. MMF offers improved immunosuppressive therapy following renal and probably other solid organ transplantation. MMF has been licensed since 1995 for the prevention of acute renal allograft rejection in most countries. It has been used in different combinations of immunosuppressive drugs and in various dosages and regimens.

Objective: To evaluate the economic implications for transplant centres, Medicare and society of treatment of corticosteroid-resistant Banff Grades I, II and III acute kidney transplant rejection with the antithymocyte globulins Thymoglobulin or Atgam., Design and Setting: This was a cost analysis of a randomised double-blind multicentre clinical trial comparing the safety and efficacy of Thymoglobulin and Atgam that was performed at 25 centres in the US in 1994 to 1996., Patients and Participants: The study enrolled 163 patients, 82 in the Thymoglobulin arm and 81 in the Atgam arm., Methods: Estimates of the cost of care from the initiation of rejection therapy to 90 days post-therapy were derived from various publicly available sources and applied to patient-specific clinical events documented in the clinical trial. Patients received either intravenous Thymoglobulin (1.5 mg/kg/day) for an average of 10 days or intravenous Atgam (15 mg/kg/day) for an average of 9.7 days., Results: On average, Thymoglobulin provided significant cost savings compared with Atgam from the perspective of society [$US5977 (1996 values); 95% confidence interval (CI) $US3719 to $US8254], Medicare ($US4967; 95% CI $US3256 to $US6678) and the transplant centre ($US3087; 95% CI $US1512 to $US4667). The overall advantage attributable to Thymoglobulin was primarily due to savings from fewer recurrent rejection treatments and less frequent return to dialysis., Conclusions: Treatment of acute renal transplant rejection with Thymoglobulin is a cost saving strategy when compared with treatment with Atgam.