Cost-Effectiveness of Rifaximin Treatment in Patients with Hepatic Encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a complication of cirrhosis of the liver causing neuropsychiatric abnormalities. Clinical manifestations of overt HE result in increased health care resource utilization and effects on patient quality of life. While lactulose has historically been the mainstay of treatment for acute HE and maintenance of remission, there is an unmet need for additional therapeutic options with a favorable adverse event profile. Compared with lactulose alone, rifaximin has demonstrated proven efficacy in complete reversal of HE and reduction in the incidence of HE recurrence, mortality, and hospitalizations. Evidence suggests the benefit of long-term prophylactic therapy with rifaximin; however, there is a need to assess the economic impact of rifaximin treatment in patients with HE. OBJECTIVE: To assess the incremental cost-effectiveness of rifaximin ± lactulose versus lactulose monotherapy in patients with overt HE. METHODS: A Markov model was developed in Excel with 4 health states (remission, overt HE, liver transplantation, and death) to predict costs and outcomes of patients with HE after initiation of maintenance therapy with rifaximin ± lactulose to avoid recurrent HE episodes. Cost-effectiveness of rifaximin was evaluated through estimation of incremental cost per quality-adjusted life-year (QALY) or life-year (LY) gained. Analyses were conducted over a lifetime horizon. One-way deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty in results. RESULTS: The rifaximin ± lactulose regimen provided added health benefits despite an additional cost versus lactulose monotherapy. Model results showed an incremental benefit of $29,161 per QALY gained and $27,762 per LY gained with rifaximin ± lactulose versus lactulose monotherapy. Probabilistic sensitivity analyses demonstrated that the rifaximin ± lactulose regimen was cost-effective ~99% of the time at a threshold of $50,000 per QALY/LY gained, which falls within the commonly accepted threshold for incremental cost-effectiveness. CONCLUSIONS: The clinical benefit of rifaximin, combined with an acceptable economic profile, demonstrates the advantages of rifaximin maintenance therapy as an important option to consider for patients at risk of recurrent HE. DISCLOSURES: This analysis was funded by Salix Pharmaceuticals, a division of Bausch Health US. Salix and Xcenda collaborated on the methods, and Salix, Xcenda, Jesudian, and Ahmad collaborated on the writing of the manuscript and interpretation of results. Bozkaya and Migliaccio-Walle are employees of Xcenda. Ahmad reports speaker fees from Salix Pharmaceuticals, unrelated to this study. Jesudian reports consulting and speaker fees from Salix Pharmaceuticals, unrelated to this study. The results from this model were presented at AASLD: The Liver Meeting 2014; November 7-11; Boston, MA.

Anticoagulation prophylaxis in orthopedic surgery: an efficiency frontier approach.

UNLABELLED: This study assesses the use of new anticoagulants for the prevention of venous thromboembolism (VTE) in patients undergoing elective orthopedic surgery using traditional cost-effectiveness analysis and efficiency frontier methodology. RATIONALE: Efficiency frontier methodology has the potential to systematically improve the information used in policy and decision making, though it is still relatively uncommon in health economics. Anticoagulation in elective orthopedic surgery provides a fitting and timely case study for examining the influence of choosing one methodology over another. METHODS: An economic model was developed to capture the relative benefits and consequences of choosing one anticoagulation strategy over another in the context of orthopedic surgery. Three novel oral anticoagulants (apixaban, rivaroxaban, dabigatran) are compared with enoxaparin 40 mg daily from the UK National Health Service perspective using traditional cost-effectiveness estimates (cost/quality-adjusted life years, cost/life years gained) and the efficiency frontier. The latter explicitly includes embolic and bleeding events as outcomes. A 5-year time horizon was adopted. RESULTS: Total discounted costs ranged from about £200 000 to £431 000 over 5 years per 1000 patients undergoing elective total hip arthroplasty, and from £243 000 to £463 000 per 1000 patients for elective total knee arthroplasty. Analysis of the efficiency frontier demonstrates that apixaban and rivaroxaban are the preferred choices, depending on the outcome examined and the type of surgery. In terms of safety, apixaban is associated with more bleeding events avoided; yet, rivaroxaban demonstrated better VTE outcomes. CONCLUSION: Traditional cost-effectiveness analysis systematically excludes information related to the safety profiles of these anticoagulants. The efficiency frontier approach presented in this study provides critical information, without substantial effort, to permit a fully informed decision by taking into account all relevant outcomes as they relate to the costs associated with treatment choice.