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.

Long-Term Management: Modern Measures to Prevent Readmission in Patients with Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a frequent indication for hospitalization and represents a common manifestation of portal hypertension and decompensated liver disease that contributes to hospital readmissions. Multiple new techniques are being evaluated to assist in preventing readmissions in these high-risk patients. Techniques to improve medication adherence are paramount. The use of telemedicine and on-demand patient assessment is likely to diminish hospitalizations for HE. Wearable technology has the potential to assist in HE diagnosis and prevent HE progression, with an anticipated diminution in hospital readmissions. This article discusses current and potential future techniques to improve outcomes in these vulnerable patients.

Value-based Pricing for Rifaximin Increases Access of Patients With Irritable Bowel Syndrome With Diarrhea to Therapy.

BACKGROUND & AIMS: Increasing drug prices lead to payer coverage restrictions, which limit access to therapy. We assessed the cost effectiveness of rifaximin in management of patients with irritable bowel syndrome with diarrhea (IBS-D) under common payer coverage restrictions and determined the maximum price at which rifaximin would be cost effective using contemporary cost-effectiveness thresholds. METHODS: A decision analytic model was constructed to evaluate quality of life, cost, and cost effectiveness of rifaximin for patients with IBS-D and complete noncoverage (insurer pays none of the drug cost), unrestricted access (insurer pays 100% of the drug cost), and formulary-restricted access (insurer pays 100% of the drug cost after for patients failed by initial therapy). The maximum cost-effective drug price was determined for each level of drug coverage using threshold analysis adjusted for willingness to pay thresholds from $50,000 to $150,000 per quality-adjusted life year (QALY). Analysis was performed from a payer perspective with a 1-year time horizon. RESULTS: Unrestricted and formulary-restricted access were more effective than complete non-coverage, resulting in additional 0.03 and 0.05 QALYs gained over noncoverage. However, unrestricted and formulary-restricted coverage were more expensive. At current drug prices, unrestricted or formulary-restricted coverage would cost an additional $1,207,136 or $171,850/QALY gained, compared to complete non-coverage. A 12% to 62% price reduction ($18.46 to $26.34/pill) for formulary-restricted access and 84% to 88% price reduction ($3.53 to $4.71/pill) for unrestricted access would be needed for rifaximin to be a cost-effective treatment strategy. Rifaximin retreatment intervals, response rates, and adverse events were important factors in sensitivity analysis. CONCLUSION: Using a decision analytic model, we show that payer coverage for rifaximin for patients with IBS-D exceeds generally accepted cost-effectiveness thresholds at current drug prices. Improved payer coverage could be justified using value-based pricing methods.

Evaluation of the cost-effectiveness of rifaximin-α for the management of patients with hepatic encephalopathy in the United Kingdom.

OBJECTIVE: Rifaximin-α 550 mg twice daily plus lactulose has demonstrated efficacy in reducing recurrence of episodes of overt hepatic encephalopathy (OHE) and the risk of hepatic encephalopathy (HE)-related hospitalizations compared with lactulose alone. This analysis estimated the cost effectiveness of rifaximin-α 550 mg twice daily plus lactulose versus lactulose alone in United Kingdom (UK) cirrhotic patients with OHE. METHOD: A Markov model was built to estimate the incremental cost-effectiveness ratio (ICER). The perspective was that of the UK National Health Service (NHS). Clinical data was sourced from a randomized controlled trial (RCT) and an open-label maintenance study in cirrhotic patients in remission from recurrent episodes of OHE. Health-related utility was estimated indirectly from disease-specific quality of life RCT data. Resource use data describing the impact of rifaximin-α on hospital admissions and length of stay for cirrhotic patients with OHE was from four single-center UK audits. Costs (2012) were derived from published sources; costs and benefits were discounted at 3.5%. The base-case time horizon was 5 years. RESULTS: The average cost per patient was £22,971 in the rifaximin-α plus lactulose arm and £23,545 in the lactulose arm, a saving of £573. The corresponding values for benefit were 2.35 quality adjusted life years (QALYs) and 1.83 QALYs per person, a difference of 0.52 QALYs. This translated into a dominant base-case ICER. Key parameters that impacted the ICER included number of hospital admissions and length of stay. CONCLUSION: Rifaximin-α 550 mg twice daily in patients with recurrent episodes of OHE was estimated to generate cost savings and improved clinical outcomes compared to standard care over 5 years.

Systematic Review of the Economic Burden of Overt Hepatic Encephalopathy and Pharmacoeconomic Impact of Rifaximin.

BACKGROUND: Hepatic encephalopathy (HE), a common neurologic complication in cirrhosis, is associated with substantial disease and economic burden. Rifaximin is a non-systemic antibiotic that reduces the risk of overt HE recurrence and overt HE-related hospitalizations. OBJECTIVE: Our objective was to provide an overview of the direct HE-related costs and cost benefits of rifaximin, lactulose, and rifaximin plus lactulose. METHODS: A systematic review of PubMed and relevant meeting abstracts was conducted to identify publications since 1 January 2007 reporting economic data related to HE and rifaximin and/or lactulose. Further, a public database and published literature were used to estimate current costs of hospitalization for overt HE, and potential cost savings of HE-related hospitalizations with rifaximin. The methodological quality of included studies was evaluated using the Drummond checklist. RESULTS: A total of 16 reports were identified for inclusion in the systematic review. Globally, HE-related direct costs ranged from $US5370 to $US50,120 annually per patient. Rifaximin was associated with shorter hospital stays and reduced healthcare costs. Rifaximin also has the potential to reduce overt HE-related hospitalization risk by 50% compared with lactulose. Rifaximin was shown to have a favourable pharmacoeconomic profile compared with lactulose (based on the incremental cost-effectiveness ratio). CONCLUSIONS: In addition to its clinical benefits (e.g. reduction in the risk of recurrence of overt HE, overt HE-related hospitalizations, favourable adverse event profile), economic data are favourable for the use of rifaximin in patients with a history of overt HE.