An economic model of 2-hour post-dose ciclosporin monitoring in renal transplantation

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 $Can46 857 for C₀ monitoring and $Can45 306 for C₂ monitoring, rising to $Can146 879 and $Can142 569 after 5 years. The predicted cost for initial hospitalisation was $Can11 280 for C ₀ and $Can10 806 for C₂ monitoring. The cost of maintenance immunosuppressive drug use, graft loss and dialysis was $Can19 098 in the C₀ group and $Can18 612 in the C ₂ group, while acute rejection treatment costs were $Can2169 and $Can1577, respectively. An additional $Can14 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 $Can1551 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.