title: The potent bile acid sequestrant colesevelam is not effective in cholestatic pruritus: results of a double-blind, randomized, placebo-controlled trial.
abstract: Colesevelam is an anion-exchange resin with a 7-fold higher bile acid-binding capacity and fewer side effects than cholestyramine, the current first-line treatment option for cholestatic pruritus. The aim of this trial was to compare the effects of colesevelam and a placebo in patients with cholestatic pruritus. In a randomized, double-blind, investigator-initiated, multicenter trial, patients with cholestatic pruritus, both treatment-naive and previously treated, received 1875 mg of colesevelam or an identical placebo twice daily for 3 weeks. The effect on pruritus was assessed with daily visual analogue scales, quality-of-life scores, and evaluations of cutaneous scratch lesions. The predefined primary endpoint was the proportion of patients with at least a 40% reduction in pruritus visual analogue scale scores. Thirty-eight patients were included, and 35 were evaluable: 17 took colesevelam, 18 took the placebo, 22 were female, 8 were treatment-naive, 14 had primary biliary cirrhosis, and 14 had primary sclerosing cholangitis. The mean serum bile acid levels were comparable between the groups before treatment (P = 0.74), but they were significantly different after treatment (P = 0.01) in favor of patients treated with colesevelam. Thirty-six percent of patients in the colesevelam group reached the primary endpoint versus 35% in the placebo group (P = 1.0). There were no significant differences between the groups with respect to pruritus scores, quality-of-life scores, and severity of cutaneous scratch lesions. Mild side effects occurred in one colesevelam-treated patient and four placebo-treated patients.
  
  
  CONCLUSIONS
  Although colesevelam significantly decreased serum bile acid levels, this trial was unable to demonstrate that it was more effective than a placebo in alleviating the severity of pruritus of cholestasis.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, the Netherlands.
authors.forename: Edith M M
authors.initials: EM
authors.lastname: Kuiper
authors.forename: Karel J
authors.initials: KJ
authors.lastname: van Erpecum
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: H Bing
authors.initials: HB
authors.lastname: Thio
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Henk R
authors.initials: HR
authors.lastname: van Buuren
mesh_terms: D000328:Adult; D000368:Aged; D000499:Allylamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000097:blood; D015209:Cholangitis, Sclerosing / Q000188:drug therapy; D002779:Cholestasis / Q000188:drug therapy*; D000069472:Colesevelam Hydrochloride; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011537:Pruritus / Q000188:drug therapy*
chemical_list: D001647:Bile Acids and Salts; D010919:Placebos; D000499:Allylamine; D000069472:Colesevelam Hydrochloride