Z Gastroenterol 2020; 58(05): e102-e103
DOI: 10.1055/s-0040-1712322
Hepatologie

Durable Response in the Markers of Cholestasis Through 5 Years of Open-Label Extension Study of Obeticholic Acid in Primary Biliary Cholangitis

E Halilbasic
1   Medical University of Vienna, Wien, Austria
,
F Nevens
2   2University Hospital KU Leuven, Leuven, Belgium
,
ML Shiffman
3   Liver Institute of Virginia, Bon Secours Mercy Health, Richmond, United States
,
JP Drenth
4   Radboud University Medical Center, Nijmegen, Netherlands
,
CL Bowlus
5   University of California, Davis, United States
,
V Vargas
6   Hospital Vall d’Hebron, Universitat Autònoma, CIBERehd, Barcelona, Spain
,
P Andreone
7   University of Bologna, Center for Research and Study of Hepatitis, Department of Medical and Surgical Sciences, Bologna, Italy
,
K van Erpecum
8   University Medical Center Utrecht, Department of Gastroenterology and Hepatology, Utrecht, Netherlands
,
A Liberman
9   Intercept Pharma Inc., San Diego, United States
,
R Pencek
10   Intercept Pharma Inc. - at the time study was conducted, San Diego, United States
,
ES Malecha
11   Retrophin, San Diego, United States
,
L MacConell
9   Intercept Pharma Inc., San Diego, United States
,
M Trauner
1   Medical University of Vienna, Wien, Austria
› Author Affiliations
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Background POISE was a placebo-controlled, phase 3 study of the efficacy and safety of obeticholic acid (OCA) in primary biliary cholangitis (PBC), with a 12-month double-blind phase and a 5-year open-label extension (OLE).

Methods During the double-blind phase, 216 patients were randomized to daily placebo, OCA 5-10 mg (titrated after 6 months based on response and tolerability), or OCA 10 mg. 193/198 patients completing the double-blind phase enrolled in the OLE and received OCA. The primary endpoint was the percentage of patients with alkaline phosphatase (ALP)  < 1.67× upper limit of normal (ULN), with a reduction of ≥ 15 % from baseline, and total bilirubin ≤ULN at 12 months. This analysis pooled double-blind placebo (OCA baseline was OLE day 0) and double-blind OCA patients to evaluate the efficacy and safety of up to 72 months of OCA treatment.

Results 146 patients (76 %) completed the protocol as specified. 158 patients (82 %) completed 4 years of OCA treatment and 116 patients (60 %) completed 5 years of OCA treatment; 52 patients who had received OCA in the double-blind phase completed 6 years on treatment. The percentage of patients meeting the primary endpoint was 46 % at 12 months and 50 % at 48, 60, and 72 months. Significant and durable reductions were observed for ALP, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase throughout the study. Mean total bilirubin remained stable through 72 months of OCA treatment. Throughout the study there was no significant worsening in hepatic stiffness as measured by transient elastography in a subset of patients. During the OLE, 8 patients (4 %) discontinued treatment due to pruritus. Adverse events were consistent with the safety profile of OCA in PBC, with no new safety observations out to 6 years.

Conclusion OCA treatment resulted in sustained improvement in liver biochemistry during up to 6 years of follow-up.



Publication History

Article published online:
26 May 2020

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