A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is typically associated with elevated serum bile acid levels and pruritus, but pruritus is often refractory to treatment with existing therapies. This phase 2 study assessed the efficacy and safety of maralixibat, a selective, ileal, apical, sodium-dependent, bile acid transporter inhibitor, in adults with PBC and pruritus. Adults with PBC and pruritus who had received ursodeoxycholic acid (UDCA) for ≥6 months or were intolerant to UDCA were randomized 2:1 to maralixibat (10 or 20 mg/day) or placebo for 13 weeks in combination with UDCA (when tolerated). The primary outcome was change in Adult Itch Reported Outcome (ItchRO™) average weekly sum score (0, no itching; 70, maximum itching) from baseline to week 13/early termination (ET). The study enrolled 66 patients (maralixibat [both doses combined], n = 42; placebo, n = 24). Mean ItchRO™ weekly sum scores decreased from baseline to week 13/ET with maralixibat (-26.5; 95% confidence interval [CI], -31.8, -21.2) and placebo (-23.4; 95% CI, -30.3, -16.4). The difference between groups was not significant (P = 0.48). In the maralixibat and placebo groups, adverse events (AEs) were reported in 97.6% and 70.8% of patients, respectively. Gastrointestinal disorders were the most frequently reported AEs (maralixibat, 78.6%; placebo, 50.0%). Conclusion: Reductions in pruritus did not differ significantly between maralixibat and placebo. However, a large placebo effect may have confounded assessment of pruritus. Lessons learned from this rigorously designed and executed trial are indispensable for understanding how to approach trials assessing pruritus as the primary endpoint and the therapeutic window of bile acid uptake inhibition as a therapeutic strategy in PBC

Thyroid Dysfunction in Primary Biliary Cholangitis: A Comparative Study at Two European Centers

open10siOBJECTIVES: Primary biliary cholangitis (PBC) is often associated with other autoimmune diseases, but little is known about the influence of thyroid disease (TD) on the natural history of PBC. Our aim is to analyze the association between PBC and TD, and the latter's impact on the natural history of PBC at two European centers. METHODS: The study involved 921 PBC patients enrolled between 1975 and 2015 in Padova (376 patients) and Barcelona (545 patients), with a mean follow-up of 126.9±91.7 months. Data were recorded on patients' histological stage at diagnosis, biochemical data, associated extrahepatic autoimmune conditions, and clinical events, including hepatic decompensation. RESULTS: A total of 150 patients (16.3%) had TD, including 94 patients (10.2%) with Hashimoto's thyroiditis; 15 (1.6%) with Graves' disease; 22 (2.4%) with multinodular goiter; 7 (0.8%) with thyroid cancer; and 12 (1.3%) with other thyroid conditions. The prevalence of different types of TD was similar in Padova and Barcelona, except for Graves' disease and thyroid cancer, which were more frequent in the Padova cohort (15.7 vs. 5.0%, and 8.6 vs. 1.3%, respectively, P<0.05). Overall, there were no differences between PBC patients with and without TD in terms of their histological stage at diagnosis, hepatic decompensation events, occurrence of HCC, or liver transplantation rate. The presence of associated TD was not associated with lower survival for PBC patients in either cohort. CONCLUSIONS: TDs, and autoimmune TD like Hashimoto's thyroiditis in particular, are often associated with PBC, but the presence of TD does not influence the rate of hepatic complications or the natural history of PBC.openFloreani, Annarosa; Mangini, Chiara; Reig, Anna; Franceschet, Irene; Cazzagon, Nora; Perini, Lisa; Caballería, Llorenç; Cocchio, Silvia; Baldo, Vincenzo; Parés, AlbertFloreani, Annarosa; Mangini, Chiara; Reig, Anna; Franceschet, Irene; Cazzagon, Nora; Perini, Lisa; Caballería, Llorenç; Cocchio, Silvia; Baldo, Vincenzo; Parés, Alber

Primary biliary cholangitis presenting as acute ischemic stroke: A rare association

Primary biliary cholangitis is associated with hyperlipidemia, but studies show that the condition does not increase cardiovascular risks. The case presents acute ischemic stroke with no underlying risk factors and subsequent new diagnosis of primary biliary cholangitis, which can suggest possible association between primary biliary cholangitis and acute stroke