Long-term Clinical Impact and Cost-Effectiveness of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis.
Hepatology. 2016 Nov 7;:
Authors: Samur S, Klebanoff M, Banken R, Pratt DS, Chapman R, Ollendorf DA, Loos AM, Corey K, Hur C, Chhatwal J
Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease that mainly affects middle-aged women. Obeticholic acid (OCA), which was recently approved by the Food and Drug Administration for PBC treatment, has demonstrated positive effects on biochemical markers of liver function. Our objective was to evaluate the long-term clinical impact and cost-effectiveness of OCA as a second-line treatment for PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA. We developed a mathematical model to simulate the lifetime course of PBC patients treated with OCA+UDCA versus UDCA alone. Efficacy data were derived from the Phase III POISE trial, and the natural history of PBC was informed by published clinical studies. Model outcomes were validated using the PBC Global Study. We found that in comparison with UDCA; OCA+UDCA could decrease the 15-year cumulative incidences of decompensated cirrhosis from 12.2% to 4.5%, hepatocellular carcinoma from 9.1% to 4.0%, liver transplants from 4.5% to 1.2%, and liver-related deaths from 16.2% to 5.7%, and increase 15-year transplant-free survival from 61.1% to 72.9%. The lifetime cost of PBC treatment would increase from $63,000 to $902,000 (1,330% increment). The discounted quality-adjusted life years (QALYs) with UDCA and OCA+UDCA were 10.74 and 11.78 respectively, and the corresponding costs were $142,300 and $633,900, resulting in an incremental cost-effectiveness ratio of $473,400/QALY gained. The results were most sensitive to the cost of OCA.
CONCLUSIONS: OCA is a promising new therapy to substantially improve the long-term outcomes of PBC patients. However, at its current annual price of $69,350, OCA is not cost-effective using a willingness-to-pay threshold of $100,000-per-QALY. Pricing below $18,450 per year, is needed to make OCA cost-effective. This article is protected by copyright. All rights reserved.
PMID: 27906472 [PubMed - as supplied by publisher]
Optimal Timing of Hepatitis C Treatment for Patients on the Liver Transplant Waiting List.
Hepatology. 2016 Nov 5;:
Authors: Chhatwal J, Samur S, Kues B, Ayer T, Roberts MS, Kanwal F, Hur C, Donnell DM, Chung RT
The availability of oral direct-acting antiviral (DAAs) has altered the hepatitis C virus (HCV) treatment paradigm for both pre- and post-liver transplant (LT) patients. There is a perceived trade-off between pre- versus post-LT treatment of HCV-treatment may improve liver function but potentially decrease the likelihood of a necessary LT. Our objective was to identify LT-eligible patients with decompensated cirrhosis who would benefit (and not benefit) from pre-LT treatment based on their MELD scores. We simulated a virtual trial comparing long-term outcomes of pre- versus post-LT HCV treatment with oral DAAs for patients having MELD scores between 10 and 40. We developed a Markov-based microsimulation model, SIM-LT (simulation of liver transplant candidates), which simulated the life course of patients on the transplant waiting list and after LT. SIM-LT integrated data from recent trials of oral DAAs (SOLAR 1 and 2), United Network for Organ Sharing (UNOS), and other studies. The outcomes of the model included life expectancy, 1-year and 5-year patient survival, and mortality. Model-predicted patient-survival was validated with UNOS data. We found that, at the national level, treating HCV before LT increased life expectancy if MELD ≤ 27, but could decrease life expectancy at higher MELD scores. Depending on the UNOS region, the threshold MELD score to treat HCV pre-LT varied between 23 and 27, and was lower for UNOS regions 3, 10 and 11, and higher for regions 1, 2, 4, 5, 8 and 9. Sensitivity analysis showed that the thresholds were stable.
CONCLUSIONS: Our findings suggest that the optimal MELD threshold below which decompensated cirrhotic patients should receive HCV treatment while awaiting LT is between 23-27, depending on the UNOS region. This article is protected by copyright. All rights reserved.
PMID: 27906468 [PubMed - as supplied by publisher]