A double-blind, placebo-controlled, randomized study of infliximab in primary sclerosing cholangitis

GOALS: To evaluate the safety and efficacy of infliximab in patients with primary sclerosing cholangitis. STUDY: In this double-blind, placebo-controlled study, 24 patients with primary sclerosing cholangitis were screened and randomly assigned in a 2:1 ratio to receive infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, 12, 18, and 24; patients were followed through week 52. The primary efficacy end point was a decrease of at least 50% in the serum alkaline phosphatase level from baseline to week 18. A blinded histologic assessment of liver biopsy samples, obtained at weeks 0 and 26, was performed using a predefined scoring system, including scores for inflammation, fibrosis, and cholestasis. RESULTS: Patient enrollment was prematurely stopped when results of an interim analysis showed no significant treatment benefit. Of the 24 patients screened, 10 were enrolled (6 patients received infliximab). Mean alkaline phosphatase levels at weeks 0, 18, and 52 were 349, 330, and 389 U/L, respectively, for the infliximab group and 481, 438, and 391 U/L, respectively, for the placebo group. Liver biopsy samples were analyzed in 7 patients (4 infliximab); no apparent differences could be detected in any of the histologic parameters. In 3 of 4 infliximab-treated patients and 2 of 3 placebo-treated patients, the disease stage did not change after 6 months of treatment. No meaningful changes were detected in the symptom score. No serious drug-related adverse events were observed. CONCLUSIONS: Study findings failed to demonstrate efficacy of infliximab in this small group of patients with established primary sclerosing cholangitis