Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection

Abstract Introduction Obeticholic acid (OCA) is a semi-synthetic hydrophobic bile acid (BA) analogue that is highly selective agonist of farnesoid X receptor (FXR), a key nuclear BA receptor, which induces expression of gut-derived hormones, in particular fibroblast growth factor 19. The resulting beneficial effects of OCA on glucose and lipid metabolism and particularly hepatic inflammation make it a candidate for the treatment of a variety of conditions including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH). Sources of data In PBC patients who have not initially responded to ursodeoxycholic acid, OCA has been shown in double-blind controlled clinical trials to significantly reduce serum alkaline phosphatase. To date, OCA is the only therapy licensed by the FDA, EMA and endorsed by NICE as second line therapy for PBC. No medications are currently approved in Europe or the USA for the treatment of NASH. In recent clinical trials, OCA has been shown encouraging results by improving liver blood tests and reducing liver fibrosis with no worsening of NASH. Areas of agreement OCA is the established second line therapy for PBC in those patients who fail to adequately respond to ursodeoxycholic acid. Areas of controversy The main side effects of OCA treatment in both PBC and NASH is that of dose-dependent pruritis which can lead to treatment discontinuation in ~1–10% of patients. In addition, OCA-treated patients may also exhibit (reversible) alterations in serum lipid levels; most notably a small decrease in high density lipoprotein cholesterol. It is not yet known whether these changes carry a long-term cardiovascular risk in NASH. In addition, the relatively high cost of OCA may limit its use in cash-limited health systems. Growing Points Additional clinical trials are in progress to ascertain the long-term effects of OCA on survival in PBC and NASH. Areas timely for developing research New FXR agonists with a lower rate of side effects are being developed and trialed. Combination therapy with other agents may offer increased efficacy.

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Obeticholic acid improves fetal bile acid profile in a mouse model of gestational hypercholanemia

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00126.2020 ◽

2020 ◽

Vol 319 (2) ◽

pp. G197-G211

Author(s):

Vanessa Pataia ◽

Saraid McIlvride ◽

Georgia Papacleovoulou ◽

Caroline Ovadia ◽

Julie A. K. McDonald ◽

...

Keyword(s):

Bile Acid ◽

Mouse Model ◽

Nonalcoholic Steatohepatitis ◽

Intrahepatic Cholestasis ◽

Primary Biliary Cholangitis ◽

Intrahepatic Cholestasis Of Pregnancy ◽

Obeticholic Acid ◽

Cholestasis Of Pregnancy

We used a mouse model of gestational hypercholanemia to investigate the use of obeticholic acid (OCA), a potent FXR agonist, as a treatment for the hypercholanemia of intrahepatic cholestasis of pregnancy (ICP). The results demonstrate that OCA can improve the fetal bile acid profile. This is relevant not only to women with ICP but also for women who become pregnant while receiving OCA treatment for other conditions such as primary biliary cholangitis and nonalcoholic steatohepatitis.

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Obeticholic Acid in Primary Biliary Cholangitis: A Meta-Analysis of Randomized Controlled Trials

The American Journal of Gastroenterology ◽

10.14309/00000434-201710001-01020 ◽

2017 ◽

Vol 112 ◽

pp. S567-S568

Author(s):

Mohsin Salih ◽

Saad Emhmed Ali ◽

Anna dela Cruz ◽

Wesam M. Frandah

Keyword(s):

Randomized Controlled Trials ◽

Meta Analysis ◽

Primary Biliary Cholangitis ◽

Controlled Trials ◽

Obeticholic Acid ◽

Randomized Controlled

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FRI-043-Primary biliary cholangitis-Autoimmune hepatitis overlap syndrome: Characteristics and response to obeticholic acid in TARGET-PBC, a diverse, large United States real-world cohort

Journal of Hepatology ◽

10.1016/s0618-8278(19)30793-5 ◽

2019 ◽

Vol 70 (1) ◽

pp. e403

Author(s):

Marlyn J. Mayo ◽

Christopher Bowlus ◽

Elizabeth Carey ◽

Ester Little ◽

Karen Deane ◽

...

Keyword(s):

United States ◽

Autoimmune Hepatitis ◽

Real World ◽

Overlap Syndrome ◽

Primary Biliary Cholangitis ◽

Obeticholic Acid

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Durable response in the markers of cholestasis through 36 months of open-label extension study of obeticholic acid in primary biliary cholangitis

Journal of Hepatology ◽

10.1016/s0168-8278(18)30665-2 ◽

2018 ◽

Vol 68 ◽

pp. S224-S225 ◽

Cited By ~ 1

Author(s):

M. Trauner ◽

F. Nevens ◽

M. Shiffman ◽

J.P.H. Drenth ◽

C. Bowlus ◽

...

Keyword(s):

Extension Study ◽

Primary Biliary Cholangitis ◽

Obeticholic Acid ◽

Open Label ◽

Durable Response ◽

Open Label Extension

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FRI-067-Management of primary biliary cholangitis in the pre-obeticholic acid era, and the rate of non-response to ursodeoxycholic acid (UDCA), in a large real-world cohort of PBC patients in Italy: The CLEO-AIGO database

Journal of Hepatology ◽

10.1016/s0618-8278(19)30817-5 ◽

2019 ◽

Vol 70 (1) ◽

pp. e415 ◽

Cited By ~ 1

Author(s):

Umberto Vespasiani Gentilucci ◽

Floriano Rosina ◽

Luchino Chessa ◽

Valeria Pace Palitti ◽

Antonio Picardi ◽

...

Keyword(s):

Ursodeoxycholic Acid ◽

Real World ◽

Primary Biliary Cholangitis ◽

Obeticholic Acid

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Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2018-000256 ◽

2019 ◽

Vol 6 (1) ◽

pp. e000256 ◽

Cited By ~ 1

Author(s):

Jennifer Pate ◽

Juilo A Gutierrez ◽

Catherine T Frenette ◽

Aparna Goel ◽

Sonal Kumar ◽

...

Keyword(s):

Liver Disease ◽

Patient Adherence ◽

Treated Patient ◽

Management Strategies ◽

Primary Biliary Cholangitis ◽

Cholestatic Liver Disease ◽

Common Symptom ◽

Obeticholic Acid ◽

Intrahepatic Bile Ducts ◽

Patient Health

Background and aimsThis article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment.MethodsIn May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice.ResultsThese recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms.ConclusionsPruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.

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