Durability of biochemical improvements through six years of open label treatment with obeticholic acid in patients with PBC who did not achieve the POISE criteria

Background In various clinical studies and in daily clinical practice, response to primary biliary cholangitis (PBC) treatment has been assessed using dichotomous biochemical response criteria. The objective of this analysis was to assess the extent and durability of obeticholic acid (OCA) in patients with PBC who did not achieve the dichotomous primary endpoint criteria in the phase 3 POISE study through 72 months of OCA treatment.

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 12 month double-blind phase, 216 patients were randomized to daily placebo, OCA 5-10, or OCA 10 mg. 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. This analysis excludes subjects who achieved the POISE primary endpoint (ALP < 1.67× ULN, with a reduction of ≥15 % from baseline, and total bilirubin ≤ULN) at 12 months. Values shown are mean (SD) unless otherwise specified. P-values were based on paired t-tests.

Results One hundred and ninety-three patients enrolled in the OLE of which 107 patients (55 %) did not achieve the POISE criteria after 12 months of OCA treatment. Patients were 93 % female, 91 % Caucasian, 56 (10) years of age at baseline and 91 % received UDCA (15 [4] mg/kg/day). At baseline, ALP was 356 (138) U/L and total bilirubin was 13 (8) µmol/L (elevated above ULN in 18 patients [17 %]). Despite not achieving the POISE criteria after 12 months of OCA, a significant and durable reduction was observed in ALP (p < 0.01 at all time points) through the duration of 72 months of treatment. Total bilirubin levels remained stable and near baseline values within the normal range through the duration of treatment. Through the 6-year study period, the most commonly occurring adverse events were pruritus (92 patients [86 %]) and fatigue (33 patients [31 %]) consistent with previous reports from POISE and expected PBC symptoms.

Conclusions Despite the fact that these patients did not achieve the POISE primary endpoint, significant and sustained biochemical improvements were observed.

Publication History

Article published online:
08 September 2020