Obeticholic acid for the treatment of hepatobiliary disorders
https://doi.org/10.24884/1609-2201-2024-103-3-50-55
Abstract
Obeticholic acid is the first-in-class selective farnesoid X receptor agonist that is approved in several countries (since August 2024, including Russia) for the treatment of primary biliary cholangitis in patients with inadequate response to monotherapy with ursodeoxycholic acid or intolerance thereof. The present paper reviews the aspects and prospects of the use of obeticholic acid in primary biliary cholangitis as well as other hepatobiliary diseases, including non-alcoholic (metabolic dysfunction-associated) steatohepatitis.
About the Authors
V. A. Prikhodko
Saint Petersburg State Chemical and Pharmaceutical University
Russian Federation
Russian Federation
Veronika A. Prikhodko, Cand. of Sci. (Biol.), Senior Lecturer of the Department of Pharmacology and Clinical Pharmacology
14A Professora Popova str., Saint Petersburg, 197376
E. A. Karelina
Saint Petersburg State Chemical and Pharmaceutical University
Russian Federation
Russian Federation
Ekaterina A. Karelina, Student of the Pharmaceutical Faculty
Saint Petersburg
S. V. Okovityi
Saint Petersburg State Chemical and Pharmaceutical University;
Saint Petersburg State University
Russian Federation
Russian Federation
Sergey V. Okovityi, Dr. of Sci. (Med.), Professor, Head of the Department of Pharmacology and Clinical Pharmacology, Saint Petersburg State Chemical and Pharmaceutical University; Professor at the Scientific and Clinical Center for Gastroenterology and Hepatology, Saint Petersburg State University
Saint Petersburg
References
1. Trivella J., John B. V., Levy C. Primary biliary cholangitis: Epidemiology, prognosis, and treatment. Hepatol Commun. 2023;7(6):e0179. https://doi.org/10.1097/HC9.0000000000000179.
2. Vinnitskaya E. V., Absandze K. G., Arkhipova E. V. et al. Primary biliary cholangitis and ursodeoxycholic acid: therapy progress and challenges. Doctor.Ru. 2019;(3(158)):33–39. (In Russ.). https://doi.org/10.31550/1727-2378-2019-158-3-33-39.
3. Chalifoux S. L., Konyn P. G., Choi G., Saab S. Extrahepatic manifestations of primary biliary cholangitis. Gut Liver. 2017;11(6):771–780. https://doi.org/10.5009/gnl16365.
4. Ivashkin V. T., Shirokova Ye. N., Mayevskaya M. V. et al. Clinical guidelines of the Russian gastroenterological association and the Russian society on study of the liver on diagnostics and treatment of cholestasis. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2015;25(2):41–57. (In Russ.).
5. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67(1):145–172. https://doi.org/10.1016/j.jhep.2017.03.022.
6. Lindor K. D., Bowlus C. L., Boyer J. et al. Primary biliary cholangitis: 2018 practice guidance from the American association for the study of liver diseases. Hepatology. 2019;69(1):394–419. https://doi.org/10.1002/hep.30145.
7. United States Food and Drugs Administration. Ocaliva (obeticholic acid): Approval label. 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf (accessed: 2.09.2024).
8. Fiorucci S., Clerici C., Antonelli E. et al. Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis. J Pharmacol Exp Ther. 2005;313(2):604–612. https://doi.org/10.1124/jpet.104.079665.
9. Jiang L., Liu X., Liang X. et al. Structural basis of the farnesoid X receptor/retinoid X receptor heterodimer on inverted repeat DNA. Comput Struct Biotechnol J. 2023;21:3149–3157. https://doi.org/10.1016/j.csbj.2023.05.026.
10. Floreani A., Gabbia D., De Martin S. Obeticholic acid for primary biliary cholangitis. Biomedicines. 2022;10(10):2464. https://doi.org/10.3390/biomedicines10102464.
11. Keshvani C., Kopel J., Goyal H. Obeticholic Acid – A pharmacological and clinical review. Future Pharmacology. 2023;3(1):238–251. https://doi.org/10.3390/futurepharmacol3010017.
12. Mi L. Z., Devarakonda S., Harp J. M. et al. Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mol Cell. 2003;11(4):1093–1100. https://doi.org/10.1016/s10972765(03)00112-6.
13. Khanna A., Jones D. E. Novel strategies and therapeutic options for the management of primary biliary cholangitis. Therap Adv Gastroenterol. 2017;10(10):791–803. https://doi.org/10.1177/1756283X17728669.
14. Nevens F., Andreone P., Mazzella G. et al. POISE Study Group. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. N Engl J Med. 2016;375(7):631–643. https://doi.org/10.1056/NEJMoa1509840
15. United States Food and Drugs Administration. Ocaliva (obeticholic acid): Package insert. 2022. URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/207999s008lbl.pdf (accessed: 2.09.2024).
16. Edwards J. E., Eliot L., Parkinson A. et al. Assessment of pharmacokinetic interactions between obeticholic acid and caffeine, midazolam, warfarin, dextromethorphan, omeprazole, rosuvastatin, and digoxin in phase 1 studies in healthy subjects. Adv Ther. 2017;34(9):2120–2138. https://doi.org/10.1007/s12325017-0601-0.
17. Real-World Data Study to Evaluate the Effectiveness of OCA on Hepatic Outcomes in PBC Patients (HEROES PBC). URL: https://www.clinicaltrials.gov/study/NCT05292872 (accessed: 2.09.2024).
18. Murillo Perez C. F., Fisher H., Hiu S. et al. Greater transplant-free survival in patients receiving obeticholic acid for primary biliary cholangitis in a clinical trial setting compared to real-world external controls. Gastroenterology. 2022;163(6):1630–1642.e3. https://doi.org/10.1053/j.gastro.2022.08.054.
19. Zhang H., Dong M., Liu X. Obeticholic acid ameliorates obesity and hepatic steatosis by activating brown fat. Exp Ther Med. 2021;22(3):991. https://doi.org/10.3892/etm.2021.10423.
20. Yan M., Hou L., Cai Y. et al. Effects of intestinal FXR-related molecules on intestinal mucosal barriers in biliary tract obstruction. Front Pharmacol. 2022;13:906452. https://doi.org/10.3389/fphar.2022.906452.
21. Obeticholic acid for prevention in Barrett’s esophagus. https://www.clinicaltrials.gov/study/NCT04939051 (accessed: 2.09.2024).
22. Testing obeticholic acid for familial adenomatous polyposis. https://www.clinicaltrials.gov/study/NCT05223036 (accessed: 2.09.2024).
23. Prikhodko V. A., Bezborodkina N. N., Okovityi S. V. Pharmacotherapy for Non-alcoholic fatty liver disease: Emerging targets and drug candidates. Biomedicines. 2022;10(2):274. https://doi.org/10.3390/biomedicines10020274.
24. Zhao J., Li B., Zhang K., Zhu Z. The effect and safety of obeticholic acid for patients with nonalcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2024;103(7):e37271. https://doi.org/10.1097/MD.0000000000037271.
25. FDA briefing document (NDA 212833). 2023. https://www.fda.gov/media/168215/download (accessed on 02 Sep 2024).
26. Comparative study between obeticholic acid versus vitamin E in patients with non-alcoholic steatohepatitis. URL: https://www.clinicaltrials.gov/study/NCT05573204 (accessed: 2.09.2024).
27. European Union drug regulating authorities clinical trials database. URL: https://eudract.ema.europa.eu/ (accessed: 2.09.2024).
28. Russian State Drug Register. Obeticholic acid. URL: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=b83541bb-0351-4d3c-b21c-4f8356742241 (accessed: 2.09.2024).
Review
For citations:
Prikhodko V.A., Karelina E.A., Okovityi S.V. Obeticholic acid for the treatment of hepatobiliary disorders. New St. Petersburg Medical Records. 2024;(3):50-55. (In Russ.) https://doi.org/10.24884/1609-2201-2024-103-3-50-55
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