title: Prospective Clinical Trial of Rifaximin Therapy for Patients With Primary Sclerosing Cholangitis.
abstract: Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease in which emerging data suggest that oral antibiotics may offer therapeutic effects. We enrolled patients with PSC in a 12-week, open-label pilot study to investigate the efficacy and safety of 550 mg of oral rifaximin twice daily. The primary end point was serum alkaline phosphatase (ALK) at 12 weeks. Secondary end points included (1) serum bilirubin, gamma-glutamyl transpeptidase, and Mayo PSC risk score; (2) fatigue impact scale, chronic liver disease questionnaire, and short form health survey (SF-36) scores; and (3) adverse effects (AEs). Analyses were performed with nonparametric tests. Sixteen patients were enrolled, among whom the median age was 40 years; 13 (81%) were male, 13 had inflammatory bowel disease, and baseline ALK was 342 IU/mL (interquartile range, 275-520 IU/mL). After 12 weeks of treatment, there were no significant changes in ALK (median increase of 0.9% to 345 IU/mL; P = 0.47) or any of the secondary biochemical end points (all P > 0.05). Similarly, there were no significant changes in fatigue impact scale, chronic liver disease questionnaire, or SF-36 scores (all P > 0.05). Three patients withdrew from the study due to AEs; 4 others reported mild AEs but completed the study. In conclusion, although some antibiotics may have promise in treating PSC, oral rifaximin, based on the results herein, seems inefficacious for this indication. Future studies are needed to understand how the antimicrobial spectra and other properties of antibiotics might determine their utility in treating PSC.
authors.affiliation: 1Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; 2Center for Clinical and Translational Sciences, Mayo Graduate School, Rochester, MN; 3Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN; 4Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN; and 5College of Health Solutions, Arizona State University, Phoenix, AZ.
authors.forename: James H
authors.initials: JH
authors.lastname: Tabibian
authors.forename: Andrea
authors.initials: A
authors.lastname: Gossard
authors.forename: Mounif
authors.initials: M
authors.lastname: El-Youssef
authors.forename: John E
authors.initials: JE
authors.lastname: Eaton
authors.forename: Jan
authors.initials: J
authors.lastname: Petz
authors.forename: Roberta
authors.initials: R
authors.lastname: Jorgensen
authors.forename: Felicity B
authors.initials: FB
authors.lastname: Enders
authors.forename: Anilga
authors.initials: A
authors.lastname: Tabibian
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lindor
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005221:Fatigue / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D011537:Pruritus / Q000209:etiology; D012294:Rifamycins / Q000627:therapeutic use*; D000078262:Rifaximin; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000890:Anti-Infective Agents; D012294:Rifamycins; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D000078262:Rifaximin; D001663:Bilirubin