Cholestatic Pruritus Treatments in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: A Systematic Literature Review

Abstract

Background and Aims We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Methods Studies that enrolled ≥ 75% participants with PBC or PSC and reported ≥ 1 endpoint(s) related to efficacy, safety, health-related quality of life (HRQoL) or other patient-reported outcomes were included. Bias was assessed using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and the Quality of Cohort studies tool for non-RCTs. Results Thirty-nine publications were identified, covering 42 studies and six treatment classes (including investigational and approved products): anion-exchange resins, antibiotics (rifampicin/derivatives), opiates, selective serotonin reuptake inhibitors, fibrates, ileal bile acid transporter inhibitors and other agents not categorised in these six classes. Across studies, median sample size was small ( n = 18), 20 studies were over 20 years old, 25 followed patients for ≤ 6 weeks, only 25 were RCTs. Pruritus was assessed using several different tools, with inconsistencies in their application. Cholestyramine, considered first-line therapy for moderate-severe cholestatic pruritus, was assessed in six studies (two RCTs) including 56 patients with PBC and 2 with PSC, with evidence of efficacy demonstrated in only three studies, among which, two RCTs were assessed as having a high risk of bias. Findings were similar for other drug classes. Conclusions There is a lack of consistent and reproducible evidence available on efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leaving physicians to rely on clinical experience rather than evidence-based medicine for treatment selection. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-023-07862-z.

Pruritus in primary biliary cholangitis is under-recorded in patient medical records

“…However, these medications were not frequently used in this analytic cohort, and clearly distinguishing fibrate use for refractory PBC versus pruritus management was not feasible in this study. Fourth, given that the majority of medications recommended to manage pruritus in the USA are used off-label, 30 it is difficult to reliably conclude that the recent antipruritic treatments documented were used for itch, which could lead to overestimating the number of patients recently receiving antipruritic therapy. Finally, the study population only included patients in the United States, which may limit generalisability of the results to other countries.…”

Cholestatic Pruritus: Pathophysiology, Current Management Approach, and Emerging Therapies

“…In the TARGET-PBC study, only 52% of patients with pruritus received any treatment for itching and a majority did not feel that their itching was adequately treated. This data and others indicate that medical providers may not be diagnosing pruritus and assessing its severity effectively in the affected patients, delaying any potential therapies [7].…”

Progress in the Management of Patients with Cholestatic Liver Disease: Where Are We and Where Are We Going?

“…The pregnane X receptor agonist rifampicin is the secondline choice for pruritus as it can alleviate pruritus in patients who are intolerant to cholestyramine or have no response to the first-line therapy. 28,29 However, rifampicin may affect coagulation function and vitamin K absorption, so it needs to be carefully tested during clinical use. The opioid receptor antagonist naltrexone is used as a third-line treatment for pruritus.…”