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
