Background & aims: Biochemical markers, including GLOBE score and aspartate aminotransferase-to-platelet ratio index (APRI), are used to stratify risk in patients with primary biliary cholangitis (PBC). This study aimed to evaluate the effects of obeticholic acid (OCA) on categorical shifts in GLOBE score, APRI, and both combined, based on data from POISE, a phase III placebo-controlled trial in patients with PBC who had an incomplete response or were intolerant to ursodeoxycholic acid.
Methods: In a post hoc analysis, baseline and Month 12 data from POISE were used to calculate the APRI and GLOBE score. Patients were stratified into 3 risk groups based on a combination of APRI (0.54) and GLOBE (0.3 or age-specific) thresholds.
Results: The analysis included 215 patients (47 low risk; 79 moderate risk; 89 high risk). Using the combined GLOBE score (threshold of 0.3) and APRI thresholds, there was improvement in ≥1 risk stage in 37% and 35% of patients in the OCA 5-10 mg and 10 mg groups, respectively, vs. 12% in the placebo group (both p <0.05). Progression occurred in 10% and 0% in the 5-10 mg and 10 mg groups vs. 37% in the placebo group. Results with GLOBE age-specific thresholds were similar.
Conclusions: Based on change in APRI and GLOBE score at 12 months, OCA treatment is associated with reduction in the predicted risk of liver-related complications in patients with PBC.
Lay summary: Primary biliary cholangitis (PBC) is a chronic disease affecting the liver. People who suffer from PBC are at risk of serious long-term complications. Information from certain blood tests can be used to estimate the likelihood of experiencing long-term complications. The results of this study showed that based on blood test results, people taking obeticholic acid, with or without ursodeoxycholic acid, for PBC were predicted to have a better outcome than those taking placebo.
Clinical trials registration: NCT01473524.
Keywords: AE, adverse event; ALP, alkaline phosphatase; APRI; APRI, aspartate aminotransferase-to-platelet ratio index; AST, aspartate aminotransferase; Cholestasis; DB, double-blind; FXR, farnesoid X receptor; IQR, inter-quartile range; LLN, lower limit of normal; LN, natural logarithm; LT, liver transplant; OCA, obeticholic acid; OR, odds ratio; PBC; PBC, primary biliary cholangitis; Risk stratification; UDCA, ursodeoxycholic acid; ULN, upper limit of normal.
© 2020 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).