Obeticholic Acid Impact on Quality of Life in Patients With Nonalcoholic Steatohepatitis: REGENERATE 18-Month Interim Analysis.

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.