WITHDRAWAL OF IMMUNOSUPPRESSION FOLLOWING PEDIATRIC LIVER TRANSPLANTATION: A MARKOV ANALYSIS

Purpose:    Long-term survivors of pediatric liver transplantation are at risk for developing complications related to post-transplant immunosuppressive medications (IS). Our aim was to determine the outcomes related to 2 strategies: continuing versus discontinuing IS in long-term survivors.

Method:    We constructed a decision analytic model to simulate survival and quality adjusted life years (QALYs) for a cohort of liver transplant recipients following a decision to withdraw (Group I) versus to continue IS (Group II). A good outcome in both groups was defined as no evidence of chronic rejection or adverse effects of IS, while a poor outcome was defined as the presence of adverse effects of IS.    Patients were at least three years post liver transplant, with no episodes of rejection in the past twelve months and without any adverse effects related to IS. If the patient had an episode of rejection after discontinuation of IS they were restarted and maintained on IS for three years before being weaned off medication again. Probabilities were assigned to the major clinical events and utilities were assigned to health states. The model had a time horizon of ten years with one-year cycles. We assumed the rate of rejection in the first year off IS to be 35% and 3% every year thereafter. Modeling software was used to randomize a cohort of one thousand patients to each decision group and evaluated survival and QALYs at ten years.

Result:    Patients in Group I had an average survival of 9.73 years compared to 9.40 years in Group II. QALYs were also higher in Group I: 9.62 QALYs vs. 8. 82 QALYs. In sensitivity analysis, the probability of developing adverse effects from IS had the greatest effect on survival in both Groups. In our hypothetical cohort, patients in Group I had a mortality rate of 4.2% vs. 11.4% in Group II. In Group I, only 5.4% developed an adverse effect from IS vs. 25.5% in Group II.

Conclusion: Our model demonstrates that in selected liver transplant recipients, withdrawing immunosuppression may be reasonable. Patients in the withdrawal group had greater survival and QALYs, and experienced a higher percentage of good outcomes. The development of poor outcomes due to the adverse effects of IS plays a major role in these differences.