Safety and tolerability of obeticholic acid in chronic liver disease: a pooled analysis of 1878 individuals

• Published in: Hepatology communications Vol. 7; no. 3; p. e0005
• Main Authors: Ng, Cheng Han, Tang, Ansel Shao Pin, Xiao, Jieling, Wong, Zhen Yu, Yong, Jie Ning, Fu, Clarissa E., Zeng, Rebecca W., Tan, Caitlyn, Wong, Gabriel Hong Zhe, Teng, Margaret, Chee, Douglas, Tan, Darren Jun Hao, Chan, Kai En, Huang, Daniel Q., Chew, Nicholas W.S., Nah, Benjamin, Siddqui, Mohammad S., Sanyal, Arun J., Noureddin, Mazen, Muthiah, Mark
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 01.03.2023; Wolters Kluwer Health/LWW
• Subjects: Chenodeoxycholic Acid - adverse effects; Humans; Longitudinal Studies; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - epidemiology; Original; Pruritus - drug therapy
• ISSN: 2471-254X; 2471-254X
• DOI: 10.1097/HC9.0000000000000005

Obeticholic acid (OCA) is a farnesoid X receptor agonist used in primary biliary cholangitis (PBC) treatment. Recent studies have expanded OCA use for NASH treatment and results from phase 3 clinical trial have shown beneficial reduction of ≥1 stage of fibrosis with no NASH worsening. However, safety concerns still preside, thus we systematically examine the safety profile of OCA in chronic liver disease. A search was conducted in Medline and Embase databases for OCA randomized controlled trials in chronic liver disease. Binary events were pooled with Paule-Mandel random effects model and proportional events were examined in a generalized linear mixed model with Clopper-Pearson intervals. A total of 8 studies and 1878 patients were analyzed. There was a 75% [risk ratio (RR): 1.75, 95% CI: 1.43-2.15, p < 0.01] increased pruritis risk. OCA increased constipation incidence (RR: 1.88, 95% CI: 1.45-2.43, p < 0.01), decreased diarrhea (RR: 0.62, 95% CI: 0.50-0.77, p < 0.01), and increased development of hyperlipidemia (RR: 2.69, 95% CI: 1.85-3.92, p < 0.01) relative to placebo. Sensitivity analysis in NASH-only studies found a dose-dependent effect with pruritis which increases to RR: 3.07 (95% CI: 1.74-5.41) at 25 mg. However, up to 9.98% (95% CI: 5.01%-18.89%) of NAFLD patients with placebo similarly experience pruritis events. Overall, 16.55% (95% CI: 6.47%-36.24%) of patients with NAFLD on OCA experienced pruritis. There was no significant increase in cardiovascular events. OCA may represent the first pharmacological treatment approved for NASH. However, pruritis, constipation, diarrhea, and hyperlipidemia were major events with evident dose-dependent effect that affect tolerability in NASH. Future long-term studies for longitudinal safety events are required.