Author information

• ¹Value Evidence, GSK, 980 Great West Road, Brentford, TW8 9GS, Middlesex, UK. helen.t.smith@gsk.com.
• ²Research and Development, GSK, PTM Severo Ochoa 2 28760, Tres Cantos, Madrid, Spain.
• ³Specialty Medicines, Global Medical Affairs, GSK, Research Triangle Park, Durham, NC, 27701, USA.
• ⁴Medicine Development, GSK, 1250 S Collegeville Rd, Collegeville, PA, 19426, USA.
• ⁵Statistics and Evidence Synthesis, Medical Decision Modeling Inc., 3500 Depauw Blvd, Suite #1037, Indianapolis, IN, 46268, USA.
• ⁶Modeling and Analytics, Medical Decision Modeling Inc., 3500 Depauw Blvd, Suite #1037, Indianapolis, IN, 46268, USA.

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.