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Reduction and stabilization of bilirubin with obeticholic acid treatment in patients with primary biliary cholangitis
Author(s) -
Parés Albert,
Shiffman Mitchell,
Vargas Victor,
Invernizzi Pietro,
Malecha Elizabeth S.,
Liberman Alexander,
MacConell Leigh,
Hirschfield Gideon
Publication year - 2020
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.14429
Subject(s) - obeticholic acid , medicine , bilirubin , placebo , gastroenterology , quartile , confidence interval , pathology , alternative medicine , receptor , agonist
Background & Aims Total bilirubin is a predictor of survival in primary biliary cholangitis, with the main elevated component being direct bilirubin. The purpose of this post hoc analysis was to assess the efficacy and safety of obeticholic acid across quartiles of varying baseline levels of direct bilirubin in the phase 3, randomized, placebo‐controlled Primary Biliary Cholangitis Obeticholic Acid International Study of Efficacy. Methods This analysis assessed patients on the basis of their baseline direct bilirubin level (divided by quartile). Biochemistry and safety outcomes were evaluated within each quartile over time. Results In the quartile with the highest baseline direct bilirubin (>5.47 µmol/L), there was a significant reduction in both direct and total bilirubin at Month 12 compared with placebo. Least squares mean (standard error) change from baseline in direct bilirubin at Month 12 was 4.17 (1.42) µmol/L for placebo, −3.48 (1.63) µmol/L for obeticholic acid 5‐10 mg and −3.66 (1.51) µmol/L for obeticholic acid 10 mg ( P < .0001, obeticholic acid vs placebo); the corresponding values for total bilirubin at Month 12 were 4.38 (1.55) µmol/L for placebo, −4.53 (1.83) µmol/L for obeticholic acid 5‐10 mg and −5.06 (1.64) µmol/L for obeticholic acid 10 mg ( P < .0001, obeticholic acid vs placebo). Conclusions Obeticholic acid treatment was associated with significant reductions in total and direct bilirubin, particularly in patients with high baseline direct bilirubin. Because raised direct bilirubin levels, even within the normal range, are predictive of survival in primary biliary cholangitis, these results suggest substantial benefits of obeticholic acid in at‐risk patients.