Defibrotide Cost-Effectiveness in Canada for the Treatment of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) with Multi-Organ Dysfunction (MOD) after HSCT

Introduction Hepatic VOD/SOS is a progressive, potentially life-threatening complication of HSCT conditioning or of nontransplant chemotherapy. Without treatment, VOD/SOS with MOD (renal and/or pulmonary dysfunction) may be associated with >80% mortality. Defibrotide (DF) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States and Canada, and to treat severe hepatic VOD/SOS post-HSCT in patients aged >1 month in the European Union. The current analysis evaluates the cost-effectiveness of DF vs best supportive care (BSC) in Canada in patients with VOD/SOS with MOD post-HSCT. Methods A Markov cost-utility model, with an acute phase and a long-term phase, with a lifetime horizon, was adapted to reflect Canadian experience regarding epidemiology, management costs, and survival expectancy; only direct medical costs were included. In the acute phase, transition probabilities were based on endpoints of Day +100 survival and complete response (CR) from a phase 3 trial. The model included 4 health states: severe VOD/SOS, CR, survival, and death. Survival in the long-term phase was extrapolated using data from the literature. Hospital costs were calculated by taking the difference in time to CR in each arm in order to estimate the expected difference in hospital days between the BSC and DF arms. The severe VOD/SOS utility value was assumed to be the same as acute liver failure and end-stage liver disease scores (0.208), and the utility for CR was set to the age-matched general population. Costs and outcomes were discounted at 1.5% per year according to government guidance. Health effects were primarily expressed in terms of quality adjusted life years (QALYs). Results The difference in estimated costs between DF and BSC was $27,396 Canadian (Table). There was a 1.5 QALY increase for DF vs BSC. The incremental cost-effectiveness ratio (ICER; cost per QALY gained) was $17,724. In the probabilistic sensitivity analysis, for willingness to pay of $30,000 and $50,000 per QALY gained, the probabilities of DF being cost-effective were 85.6% and 100%, respectively, (Figure). Conclusions These results suggest that DF treatment for VOD/SOS with MOD is a cost-effective use of health resources in Canada, with an estimated ICER vs BSC below the accepted threshold for willingness to pay. Limitations include longer-term extrapolation of clinical trial data and assumptions about resource utilization patterns. Results were driven by estimates of more rapid recovery, reduced length of stay, and improved Day +100 survival in DF-treated patients. Results were supported by the sensitivity analysis. Support Jazz Pharmaceuticals.

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