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.
