Z Gastroenterol 2020; 58(08): e163-e164
DOI: 10.1055/s-0040-1716170
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Durable response in the markers of cholestasis through 5 years of open-label extension study of obeticholic acid in primary biliary cholangitis

C Rupp
1   Klinik für Gastroenterologie, Infektionen, Vergiftungen, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
,
F Nevens
2   University Hospital KULeuven, Leuven, Belgien
,
Shiffman ML
3   Liver Institute of Virginia, Bon Secours Mercy Health, Newport News, Vereinigte Staaten von Amerika
,
Drenth JPH
4   UMC St. Radboud, Nijmegen, Niederlande
,
CL. Bowlus
5   University of California, Davis, Sacramento, Vereinigte Staaten von Amerika
,
V Vargas
6   Hospital Vall d’Hebron, Universitat Autònoma, CIBERehd, Barcelona, Spanien
,
P Andreone
7   Center for Research and Study of Hepatitis, University of Bologna, Department of Medical and Surgical Sciences, Bologna, Italien
,
K van Erpecum
8   University Medical Center Utrecht, Department of Gastroenterology and Hepatology, Utrecht, Niederlande
,
A Liberman
9   Intercept Pharmaceuticals, Inc., San Diego, Vereinigte Staaten von Amerika
,
R Pencek
10   Retrophin, San Diego, Vereinigte Staaten von Amerika
,
E Smoot Malecha
9   Intercept Pharmaceuticals, Inc., San Diego, Vereinigte Staaten von Amerika
,
L Mac Conell
9   Intercept Pharmaceuticals, Inc., San Diego, Vereinigte Staaten von Amerika
,
M Trauner
11   Medical University of Vienna, Vienna, Österreich
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Background Obeticholic acid (OCA) is a selective and potent farnesoid X receptor agonist indicated for treatment of primary biliary cholangitis (PBC). POISE was a placebo-controlled, phase 3 study of the efficacy and safety of OCA in PBC, and included a 12-month double-blind phase with a 5-year open-label extension (OLE).

Methods Key inclusion criteria included PBC diagnosis, alkaline phosphatase (ALP) ≥1.67× upper limit of normal (ULN) and/or total bilirubin >ULN to < 2× ULN, and on a stable dose of—or intolerant of—UDCA. 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 POISE composite primary endpoint was the percentage of patients with ALP < 1.67× 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 following administrative shutdown of the study. 158 patients (82%) completed 4 years of OCA treatment and 116 (60%) patients 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 (Table). 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 established safety profile of OCA in PBC, with no new safety observations during long term treatment 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:
08 September 2020

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