Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: a 1-year randomized, placebo-controlled study

Background/Aims: Treatment with ursodeoxycholic acid has been shown to decrease the rate of disease progression in patients with primary biliary cirrhosis, although the effect is modest. Since primary biliary cirrhosis has many features of an autoimmune disorder, immunosuppressives added to ursodeoxycholic acid may be of value in the treatment of primary biliary cirrhosis. Methods: A 1-year randomized, double-blind, placebo-controlled trial was carried out in 50 patients with primary biliary cirrhosis, who had already been treated with ursodeoxycholic acid for at least 1 year, but had not achieved complete disease remission. Patients were randomized to additional prednisone (30 mg per day initially, tapered to 10 mg daily after 8 weeks) and azathioprine (50 mg daily) or placebo. A subgroup of patients received cyclical etidronate and calcium. The principal aim of the study was to assess the short-term benefits and risks of the combined bile acid and low-dose immunosuppressive regimen. Primary endpoints were effects on symptoms, liver biochemistry, liver histology, bone mass and the occurance of adverse events. Results: Pruritus (p=0.02), alkaline phosphatase, aspartate aminotrasferase, IgM and procollaen-III-propeptide improved significantly (all p<0.002) in the combined treatment group as compared to the placebo group. Histological scores for disease activity and disease stage decreased significanty within the combination treatment group (P<0.001). Conclusions: In patients with primary biliary cirrhosis receiving beneficial ursodeoxycholic acid, there is an additional beneficial effect of 1-year treatment with prednisone and azathioprine on symptoms and biochemical, fibrogenetic and histogical parameters. These results strongly encourage the evaluation of this triple treatment regimen in long-term controlled trials of adequate size to document its effect on clinical events.