Lifetime cost-effectiveness of calcineurin inhibitor withdrawal after de novo renal transplantation

Abstract

After renal transplantation, immunosuppressive regimens associated with high short-term survival rates are not necessarily associated with high long-term survival rates, suggesting that regimens may need to be optimized over time. Calcineurin inhibitor (CNI) withdrawal from a sirolimus-based immunosuppressive regimen may maximize the likelihood of long-term graft and patient survival by minimizing CNI-associated nephrotoxicity. In this study, a lifetime Markov model was created to compare the cost-effectiveness of a sirolimus-based CNI withdrawal regimen (sirolimus plus steroids) with other common CNI-containing regimens in adult de novo renal transplantation patients. Long-term graft survival was estimated by renal function and data from published studies and the US transplant registry, including short- and long-term outcomes, utility weights, and health-state costs were incorporated. Drug costs were based on average daily consumption and wholesale acquisition costs. The model suggests that treatment with sirolimus plus steroids is more efficacious and less costly than regimens consisting of a CNI, mycophenolate mofetil, and steroids; therefore, CNI withdrawal not only shows potential for long-term clinical benefits but also is expected to be cost-saving over a patient's life compared with the most commonly prescribed CNI-containing regimens.

Figure 1.

Reported patient survival compared with patient survival as estimated in the cost-effectiveness model. ♦, Reported cadaveric-donor patient survival; ▪, reported living-donor patient survival; ▴, reported patient survival for all donor types; dashed lines, modeled cadaveric-donor patient survival; solid lines, modeled living-donor patient survival; dotted lines, modeled patient survival for all donor types. Figure shows patient survival after transplantation for patients receiving grafts from various donor types as reported by the cost-effectiveness model. These data are compared with the patient survival after transplantation for patients receiving grafts from various donor types, as reported by the OPTN/SRTR, as an example of model predictability.

Figure 2.

One-way sensitivity analysis of changes in the incremental cost per QALY. (A) Cost-effectiveness of SRL+ST versus MMF+Tac+ST. (B) Cost-effectiveness of MMF+CsA+ST versus MMF+Tac+ST. Tornado diagrams examine the changes in cost-effectiveness across the range of plausible values for each input.

Figure 3.

One-way sensitivity analysis of changes in the incremental cost per QALY versus MMF+Tac+ST for increases and decreases in the mean serum creatinine concentrations for model immunosuppressive regimens. (A) Increase in mean serum creatinine concentration for SRL+ST and MMF+CsA+ST with a stable value for MMF+Tac+ST. (B) Decrease in mean serum creatinine concentration for MMF+Tac+ST with stable values for SRL+ST and MMF+CsA+ST. Figures show a threshold analysis of changes in cost-effectiveness as increases or decreases in mean serum creatinine levels occur. In A, changes in cost-effectiveness are shown as mean serum creatinine increases for patients treated with SRL+ST and MMF+CsA+ST, while mean serum creatinine is maintained at its baseline value for patients treated with MMF+Tac+ST. In B, changes in cost-effectiveness are shown as mean serum creatinine decreases for patients treated with MMF+Tac+ST, while mean serum creatinine is maintained at its baseline value for patients treated with SRL+ST and MMF+CsA+ST.

Figure 4.

Two-part model structure of maintenance of renal transplant: First-year and subsequent-year management. (A) Decision tree for the first year after transplantation. (B) Markov model for years subsequent to the first year after transplantation. Adult de novo transplant patients progress through one focused phase of treatment. In the first year after transplantation (phase 1: decision tree [A]), patient outcomes result in one of four outcomes. Surviving patients enter phase 2 (Markov [B]), on the basis of renal function measures, and progress through four health states for the remainder of their lifetimes. SC, serum creatinine level.