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

Abstract

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.

A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis

“…Severe pruritus was also the most common severe TEAE during the LTSE (reported in 15% of patients, with 3 patients discontinuing due to pruritus that began during the LTSE). Pruritus has been shown to be manageable in other diseases 18 and the apparent dose-dependent relationship between OCA, pruritus, and clinical response in PSC should be further evaluated.…”

“…13,16,17 Currently, OCA is approved for the treatment of PBC in combination with UDCA in adults with an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. 18 Recent phase II studies have used serum ALP as an efficacy endpoint for the assessment of novel therapies in PSC, and a study of UDCA to improve ALP has been proposed by the American College of Gastroenterology guidance on PSC. 3,8,15 Based on the known biological effects of FXR activation 12,14 and the efficacy of OCA for treating PBC, 13 OCA has been selected to be studied in patients with PSC.…”

“… 13 , 16 , 17 Currently, OCA is approved for the treatment of PBC in combination with UDCA in adults with an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. 18 …”

Critical roles of bile acids in regulating intestinal mucosal immune responses

“…Indeed, severe and adverse drug side effects emerged, such as pruritus, gastrointestinal problems, increased risk of acute liver decompensation, and increased low-density lipoprotein cholesterol levels that was related to increasing cardiovascular risk. 148 – 150 Similarly, application of GPBAR1 agonists for drug development has been hindered by side effects including inhibition of gallbladder emptying, diarrhea, itching, and other syndrome. 151 One of the potential mechanisms causing pruritus during chronic OCA administration could be imputable to OCA residual activity toward GPBAR1.…”

Bioequivalence and Pharmacokinetic Profiles of Generic and Branded Obeticholic Acid in Healthy Chinese Subjects Under Fasting and Fed Conditions

“…These main ADRs were consistent with those reported in previous studies. [18][19][20] Comparing the incidence of ADRs between reference drug and test drug in the fasting and fed groups, there was no significant difference in the incidence between the two drugs, indicating that the safety of the two drugs was similar.…”