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UDCA did not improve survival for patients with primary sclerosing cholangitis

Patients with primary sclerosing cholangitis treated with ursodeoxycholic acid did not exhibit significantly greater long-term survival compared with patients who received placebo, although reduced alkaline phosphatase levels, regardless of treatment, extended survival in a recent study.

In a randomized, double blind, placebo-controlled trial, researchers investigated 198 patients with primary sclerosing cholangitis (PSC) and the effect ursodeoxycholic acid (UDCA) had on survival. Patients in Scandinavia were randomly assigned 17 mg/kg to 23 kg/mg UDCA daily (n=97) or placebo (n=101) from 1996 to 2001, and follow-up was conducted in 2010.

Researchers measured patients’ alkaline phosphatase (ALP) serum levels at baseline and every 6 months throughout the study. Patients whose ALP levels decreased at least 40% or were normal (0.8-4.6 microkat/L) after 1 year were considered biochemical responders. Endpoints were mortality, liver transplantation or cholangiocarcinoma.

Treated and untreated patients were similar in age, sex, PSC duration and symptoms, mean ALP, concomitant IBD and UDCA therapy after the 5-year study period at baseline. At follow-up, 26 UDCA and 29 placebo patients reached endpoints; 29 had liver transplantation, 14 died and 12 were diagnosed with cholangiocarcinoma.

No differences were detected in survival between UDCA and placebo patients (P=.774, log rank). Forty-three UDCA patients were considered ALP responders after 1 year and showed greater long-term outcomes than nonresponders (n=51) whose ALP levels did not decrease (P=.033, log rank). Regardless of treatment, patients who experienced ALP reductions survived longer than those considered nonresponders (P=.0001, log rank). At 12 years’ survival, the cumulative proportion of ALP responders was 0.9, compared with 0.47 among nonresponders.

“Five-year treatment with UDCA 17-23 mg/kg/day does not improve long-term survival of patients with PSC,” the researchers concluded. “A reduction in ALP or normal levels for at least 1 year is associated with a better prognosis, regardless of UDCA treatment. ALP is a possible surrogate marker for disease progression and should be considered for further evaluation as an endpoint in clinical trials in PSC.”