Cost-effectiveness analysis of rifaximin-α administration for the reduction of episodes of overt hepatic encephalopathy in recurrence compared with standard treatment in France

Abstract

Background: Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that occurs most often in a context of acute or chronic liver disease. Despite the seriousness of the pathology, only a few treatments have been developed for improving its management. Rifaximin-α is the first treatment that has been clinically developed for overt HE (OHE) episodes. Recent results of clinical studies demonstrated its significant improvement in the health-related quality of life. The objective of the current study was to estimate the long-term cost-effectiveness of rifaximin-α used in combination with lactulose compared with lactulose monotherapy in cirrhotic patients, who have experienced at least two prior OHE events.

Methods: A Markov model was used to estimate rifaximin-α cost-effectiveness, evaluating it from the perspective of all contributors as recommended by French health technology assessment guidelines. Costs were based on current French treatment practices. The transition between health states was based on the reanalysis of the rifaximin-α pivotal clinical trials RFHE3001 and RFHE3002. The main outcome of the model was cost per quality adjusted life year (QALY).

Results: The results indicate that rifaximin-α is a cost-effective treatment option with an incremental cost per QALY gained of €19,187 and €18,517 over two different time horizons (2 and 5 years). The robustness of the model was studied using probabilistic sensitivity analysis.

Conclusion: For the societal willingness to pay threshold of €27,000 per QALY gained, rifaximin-α in combination with lactulose is a cost-effective and affordable treatment for patients who have experienced at least two prior overt HE episodes.

Keywords: Markov chains; cost–benefit analysis; hepatic encephalopathy; lactulose; rifaximin.

Figure 1.

Model structure overview. 1: Patients enter the model in the remission state. 2: Covert state (CHE1) to first-observed overt episode (OHE1). 3: Covert state (CHE1) to death. 4: First-observed overt episode (OHE1) to death. 5: Recovery from first-observed overt episode to subsequent covert state (CHE2). 6: Subsequent covert state to subsequent overt episode (OHE2). 7: Subsequent covert state to death. 8: Subsequent overt episode to death. 9: Recovery from subsequent overt episode to subsequent covert state.

Figure 2.

Comparison of original Kaplan–Meier plot and corresponding best-fit parametric survival function (log-normal) for time to first overt HE event (by treatment arm in the RFHE3001 study).

Figure 3.

Tornado analysis. The value of each variable increased and reduced by 20% or 15%; in order to create the tornado diagram around the base-case incremental cost-effectiveness ratio (ICER) result (€18,517).

Figure 4.

Cost-effectiveness plane of rifaximin-α versus placebo monotherapy. The horizontal axis displays the gain on additional quality-adjusted life years (QALYs) when using rifaximin-α instead of placebo, and the vertical axis displays the additional costs. For example, if a payer had a budget of €27,000 per QALY gained, then through all Monte Carlo simulations (broken line) only 0.2% of the cohort would fall within the budget.

Figure 5.

Cost-effectiveness acceptability curve and cost-effectiveness acceptability frontier based on incremental cost-effectiveness ratio (ICER) between rifaximin-α and a placebo comparator. The horizontal axis displays the willingness-to-pay budgetary thresholds to gain one additional quality-adjusted life year (QALY) when using rifaximin-α, and the vertical axis displays the percentage of 1000 patients that fall within the available budget. The switch point where rifaximin-α became a cost-effective treatment corresponds to €12,985 per QALY gained.