Demographic Subgroup Analysis of the POISE Trial Results: Long-Term Efficacy and Safety of Obeticholic Acid in Primary Biliary Cholangitis Patients
Introduction
The phase 3, randomized controlled POISE trial assessed the safety and efficacy of obeticholic acid (OCA) in patients with primary biliary cholangitis (PBC). The primary endpoint was alkaline phosphatase (ALP) of less than 1.67 times the upper limit of normal (ULN), a reduction of at least 15% in ALP from baseline, and normal total bilirubin (≤ ULN) at 12 months. This was met by 46% of patients in the 5-mg to 10-mg OCA arm and by 47% of patients in the 10-mg OCA arm, compared with 10% of patients in the placebo arm. Patients also exhibited significant reduction in levels of ALP, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT), and stabilization of total bilirubin after 12 months of OCA treatment.
Aim
This study aimed to analyze the long-term efficacy and safety of OCA in demographic subgroups of patients who had been treated for 5 or more years in the POISE trial.
Method
Study Design
- Demographic subgroup analysis of phase 3 randomized controlled POISE trial.
Treatment Strategy
- Demographic subgroups included
- age at study entry (<55 yrs or >55 yrs)
- age when diagnosed with PBC (<47.5 yrs or >47.5 yrs)
- gender
- A total of 193 patients completed the double-blind phase and entered the open-label extension
- Among these patients, 116 completed 5 years of OCA treatment, of whom 52 completed had received OCA in the double-blind phase, resulting in 6 years of OCA treatment
End Points
- Improvements in ALP, ALT, AST, and GGT levels
- Bilirubin levels
- Adverse events (AEs)
Results
- All the subgroups demonstrated normal bilirubin and improvements in ALP after 6 years of OCA treatment
- The improvements in levels of ALT and GGT achieved during the early phase of study were sustained by across all the subgroups
- The 2 younger-age subgroups had higher ALT and AST levels as compared to other subgroups
- Mild to moderate pruritus was the most common AE reported by all the subgroups and the incidence was similar.
- There were no new safety concerns reported.
Conclusions
- Long-term treatment with obeticholic acid (OCA) is associated with durable improvements in ALP, ALT, AST and GGT as well as stabilization of normal bilirubin in patients with primary biliary cholangitis (PBC), irrespective of age or sex.
Gastroenterol Hepatol. 2021 Feb;17(2).
