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, investigatorinitiated, 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-oflife 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 5 0.74), but they were significantly different after treatment (P 5 0.01) in favor of patients treated with colesevelam. Thirtysix percent of patients in the colesevelam group reached the primary endpoint versus 35% in the placebo group (P 5 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 placebotreated patients. Conclusion: 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. (HEPATOLOGY 2010;52:1334-1340) P ruritus is a frequent and debilitating symptom of cholestatic liver disease. 1 Although the pathophysiology of pruritus secondary to cholestasis remains largely unknown, it is widely assumed that bile acids are etiologically involved. 2,3 The principal pharmacological treatment options currently available and recommended in recent guidelines 4 are cholestyramine 5,6 (a nonabsorbable, bile acid-binding resin), rifampicin, 7,8 naltrexone, 9,10 and sertraline. 11 However, the efficacy of these drugs is variable, and side effects are common. Cholestyramine frequently causes constipation and nausea, rifampicin is known for its potential hepatotoxicity, and patients on naltrexone may experience symptoms of endogenous opioid-withdrawal syndrome. Therefore, the treatment of cholestatic pruritus is currently often problematic and unsatisfactory, and alternative treatment options are warranted.
Colesevelam (Cholestagel) is a bile acid sequestrant taken in tablet form that hydrates to a gel and is being