Browsing by Author "Bowlus, Christopher L."

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    Application of the Latest Advances in Evidence-Based Medicine in Primary Biliary Cholangitis
    (Wolters Kluwer, 2023) Kowdley, Kris V.; Bowlus, Christopher L.; Levy, Cynthia; Mayo, Marlyn J.; Pratt, Daniel S.; Vuppalanchi, Raj; Younossi, Zobair M.; Medicine, School of Medicine
    Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune liver disease that can progress to end-stage liver disease and its complications. A previous expert review panel collaborated on a consensus document for gastroenterologists and other healthcare professionals regarding the care of patients with PBC. Subsequently, there have been several recent important developments in the diagnosis, treatment, and monitoring of patients with PBC. These include updates to prognostic models on risk stratification, new noninvasive tools for staging of disease, updates to the appropriate use of and long-term treatment results with obeticholic acid as a second-line treatment, the emerging therapeutic role of fibrates, and the advancement of investigational agents for managing PBC. In this updated expert consensus document, we provide updates on staging, the use of noninvasive prognostic tools, and a treatment algorithm to provide evidence-based and practical tools for clinicians who manage PBC, with the ultimate goal to improve the long-term outcomes for patients with this chronic liver disease.
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    A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis
    (Elsevier, 2020-07) Kowdley, Kris V.; Vuppalanchi, Raj; Levy, Cynthia; Floreani, Annarosa; Andreone, Pietro; LaRusso, Nicholas F.; Shrestha, Roshan; Trotter, James; Goldberg, David; Rushbrook, Simon; Hirschfield, Gideon M.; Schiano, Thomas; Jin, Yuying; Pencek, Richard; MacCone, Leigh; Shapiro, David; Bowlus, Christopher L.; Medicine, School of Medicine
    Background & aims: Primary sclerosing cholangitis (PSC) is a rare, cholestatic liver disease with no currently approved therapies. Obeticholic acid (OCA) is a potent farnesoid X receptor (FXR) agonist approved for the treatment of primary biliary cholangitis. We investigated the efficacy and safety of OCA in patients with PSC. Methods: AESOP was a phase II, randomized, double-blind, placebo-controlled, dose-finding study. Eligible patients were 18 to 75 years of age with a diagnosis of PSC and serum alkaline phosphatase (ALP) ≥2× the upper limit of normal (ULN) and total bilirubin <2.5× ULN. Patients were randomized 1:1:1 to receive placebo, OCA 1.5-3.0 mg, or OCA 5-10 mg once daily for a 24-week, double-blind phase followed by a 2-year, long-term safety extension (LTSE). Primary endpoints were change in ALP from baseline to week 24, and safety. Results: The intent-to-treat population comprised 76 patients randomized to placebo (n = 25), OCA 1.5-3.0 mg (n = 25), and OCA 5-10 mg (n = 26). At week 24, serum ALP was significantly reduced with OCA 5-10 mg vs. placebo (least-square [LS] mean difference = -83.4 [SE = 40.3] U/L; 95% CI -164.28 to -2.57; p = 0.043). Serum ALP was not significantly reduced with OCA 1.5-3.0 mg vs. placebo at week 24 (LS mean [SE] difference = -78.29 [41.81] U/L; 95% CI -162.08 to 5.50; p = 0.067). Total bilirubin remained comparable to baseline in all groups. The most common treatment-emergent adverse event was dose-related pruritus (placebo 46%; OCA 1.5-3.0 mg 60%; OCA 5-10 mg 67%). Reductions in ALP were maintained during the LTSE, and no new safety signals emerged. Conclusions: Treatment with OCA 5-10 mg reduced serum ALP in patients with PSC. Mild to moderate dose-related pruritus was the most common adverse event.