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Abstract Details
Obeticholic Acid Impact on Quality of Life in Patients With Nonalcoholic Steatohepatitis: REGENERATE 18-Month Interim Analysis
Zobair M Younossi1, Maria Stepanova2, Fatema Nader2, Rohit Loomba3, Quentin M Anstee4, Vlad Ratziu5, Stephen Harrison6, Arun J Sanyal7, Jörn M Schattenberg8, A Sidney Barritt9, Mazen Noureddin10, Martin Bonacci11, Gail Cawkwell11, Bruce Wong11, Mary Rinella12, REGENERATE Study Investigators
Author information
1Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States; Center for Liver Diseases, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, United States. Electronic address: zobair.younossi@inova.org.
2Center for Outcomes Research in Liver Disease, Washington, DC, United States.
3University of California, San Diego, San Diego, CA, United States.
4Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom & Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom.
5Sorbonne Université, Institute of Cardiometabolism and Nutrition, Hôpital Pitié - Salpêtrière, INSERM UMRS 1138 CRC, Paris, France.
6Pinnacle Clinical Research Center, San Antonio, TX, United States.
7Virginia Commonwealth University, Richmond, VA, United States.
8Department of Medicine, University Medical Center, Mainz, Germany.
9University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
10Cedars-Sinai Medical Centre, Los Angeles, CA, United States.
11Intercept Pharmaceuticals, New York, NY, United States.
12Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Abstract
BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) affects patients' health-related quality of life (HRQoL). Patient-reported outcomes (PROs) evaluating HRQoL were assessed in the REGENERATE study, which demonstrated that obeticholic acid (OCA) significantly improved fibrosis in patients with NASH.
Methods: Noncirrhotic NASH patients in a phase 3, double-blind, randomized, placebo-controlled, multicenter, international study of OCA. Chronic Liver Disease Questionnaire-NASH (CLDQ-NASH) and EuroQol EQ-5D-5L (EQ-5D) were administered at baseline, 6, 12, and 18 months.
Results: There were 1,218 patients (age, 54.1±11.5 years; 57% female; 43% F3) in the expanded ITT population (F1-F3) randomly assigned to 10 mg (N=407) or 25 mg (N=404) OCA or placebo (N=407). Baseline measurements were balanced across treatment groups for EQ-5D and CLDQ-NASH, including Itch score: 5.75±1.53 (scale 1-7, 7 representing no itching). Nineteen (1.6%) patients discontinued therapy (protocol mandated) due to grade 3 pruritus. Patients receiving OCA 25 mg experienced mild worsening of itch scores primarily in the first months of treatment: mean±standard error change from baseline -0.66±0.12, -0.44±0.12, and -0.42±0.13 at 6, 12, and 18 months, respectively (all p<0.01). No other PRO worsening was associated with OCA 25 mg. Patients experiencing fibrosis improvement, Nonalcoholic Fatty Liver Disease Activity Score decrease (by ≥2 points), or NASH resolution had greater PRO improvements in some domains.
Conclusions: NASH patients evaluated in REGENERATE had impaired quality of life and underlying pruritus at baseline. Improvement of NASH corresponded with improvement in several HRQoL domains. Generally mild pruritus occurs early after OCA therapy initiation and does not worsen over time. ClinicalTrials.gov, Number NCT02548351.