Long-Term Efficacy and Safety of Obeticholic Acid in Patients With PBC From POISE Grouped by Risk of Disease Progression

Question Primary biliary cholangitis (PBC) is a rare liver disease characterized by chronic cholestasis, fibrosis, and cirrhosis. Obeticholic acid (OCA) is approved as second-line treatment for PBC in patients who are incomplete responders or intolerant to ursodeoxycholic acid. Elevated alkaline phosphatase (ALP) and bilirubin levels predict long-term outcomes in PBC. We evaluated the long-term efficacy and safety of OCA in subgroups from the POISE trial categorized biochemically by risk of disease progression.

Methods The phase 3, randomized, double-blind, 12-month POISE trial evaluated OCA vs placebo in patients with PBC; a 5-year open-label extension followed. We evaluated OCA efficacy and safety in 2 patient subgroups based on baseline biochemical status: ALP ≤3X upper limit of normal (ULN) vs ALP  > 3X ULN and total bilirubin ≤ULN vs total bilirubin  > ULN. OCA response was ALP  < 1.67X ULN, total bilirubin ≤ULN, and ALP decrease of ≥15 % from OCA baseline.

Results Both subgroup analyses included 193 patients (ALP ≤3X ULN = 142; ALP  > 3X ULN = 51; total bilirubin ≤ULN = 172; total bilirubin  > ULN = 21). Mean (SD) ALP levels (U/L) at OCA baseline were 257.0 (45.8) in the ALP ≤3X ULN group and 484.5 (103.4) in the ALP  > 3X ULN group. Mean total bilirubin levels (μmol/L) at OCA baseline were 9.6 (4.0) in the total bilirubin ≤ULN group and 27.3 (6.0) in the total bilirubin  > ULN group. Mean change from baseline was ‒266.3 U/L in the ALP  > 3X ULN group versus ‒63.9 U/L in the ALP ≤3X ULN group at month 72. Total bilirubin levels remained stable within the total bilirubin ≤ULN group and decreased in the total bilirubin  > ULN group (Figure). Pruritus was the most frequently reported adverse event in all 4 subgroups (88 % in the ALP  > 3X ULN group; 74 %–78 % in other groups). Discontinuations due to pruritus were 3 %‒8 % in both ALP and the total bilirubin ≤ULN groups; none occurred in the total bilirubin  > ULN group.

Conclusions OCA treatment was safe and efficacious and resulted in durable improvements in markers of hepatic injury and cholestasis, regardless of baseline ALP and total bilirubin levels. Strong biochemical improvements with OCA were achieved in patients with elevated levels of ALP and bilirubin.

Figure. Mean (SD) Change From OCA Baseline to Month 72 in ALP and Total Bilirubin in Patients Grouped Biochemically by Risk of Disease Progression

Publication History

Article published online:
04 January 2021