Cost-effectiveness analysis of prophylaxis duration following lung transplantation for CMV mismatch and non-mismatch recipients

Abstract

Survival following lung transplantation is lower than survival following all other solid organ transplants. Chronic rejection, graft failure, and opportunistic infections all contribute to these poor outcomes. One such opportunistic infection is cytomegalovirus (CMV). CMV is one of the most common infections after lung transplant, and can cause direct effects (viremia and disease), and indirect effects including increased risk of acute cellular rejection, and death. Donor CMV serology positive, recipient negative (D+/R-) patients have the highest risk for developing CMV, for which they receive extended valganciclovir prophylaxis. Longer prophylaxis durations, however, may lead to an increased risk of infection due to resistant CMV, and no standardized guidelines exist for prophylaxis duration. To investigate the effect of duration length on survival, a cost-effectiveness analysis of mismatch and non-mismatch patients was performed, where non-mismatch patients received 6 months of prophylaxis and mismatch patients received either 1 or 2 years. A Markov-state transition model was used, with month-long cycles over a five-year time horizon, a 3% discount rate, and took a healthcare system perspective. Health states of no CMV, sensitive and resistant CMV viremia, sensitive and resistant CMV disease, and death are modeled, with possible episodes of acute cellular rejection in each state. Outcomes included life-years gained and quality-adjusted life-years (QALYs). The model showed that increasing prophylaxis duration resulted in gains in both life-years and QALYs. Incremental cost-effectiveness ratios were $110,510 per life-year gained and$150,280 per QALY. Continued prophylaxis for 5 years after transplant increases the ICER to $153,862 per life-year gained, and$203,756 per QALY. These results show that extended valganciclovir prophylaxis for mismatch patients is associated with gains of life-years and QALYs, and is economically reasonable. As only a limited number of lungs are available, and the demand outweighs the supply, extended prophylaxis would result in these organs being used to their greatest benefit, and could decrease the need for re-transplants, showing a clear public health impact