Cyclosporin A for primary biliary cirrhosis

Abstract

BACKGROUND: Cyclosporin A has been used for patients with primary biliary cirrhosis, but the therapeutic responses in randomised clinical trials have been heterogeneous. OBJECTIVES: To assess the beneficial and harmful effects of cyclosporin A for patients with primary biliary cirrhosis. SEARCH STRATEGY: Relevant randomised clinical trials were identified by searching The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, The Chinese Biomedical Database, and LILACS, and manual searches of bibliographies to June 2006. We contacted authors of trials and the company producing cyclosporin A. SELECTION CRITERIA: Randomised clinical trials comparing cyclosporin A with placebo, no intervention, or another drug were included irrespective of blinding, language, year of publication, and publication status. DATA COLLECTION AND ANALYSIS: Our primary outcomes were mortality, and mortality or liver transplantation. Dichotomous outcomes were reported as relative risk (RR) and if appropriate, Peto odds ratio with 95% confidence interval (CI). Continuous outcomes were reported as weighted mean difference (WMD) or standardised mean difference (SMD). We examined intervention effects by random-effects and fixed-effect models. MAIN RESULTS: We identified three trials with 390 patients that compared cyclosporin A versus placebo. Two of them were assessed methodologically adequate with low-bias risk. Cyclosporin A did not significantly reduce mortality risk (RR 0.92, 95% CI 0.59 to 1.45), and mortality or liver transplantation (RR 0.85, 95% CI 0.60 to 1.20). Cyclosporin A significantly improved pruritus (SMD -0.38, 95% CI -0.63 to -0.14), but not fatigue. Cyclosporin A significantly reduced alanine aminotransferase (WMD -41 U/L, 95% CI -63 to -18) and increased serum albumin level (WMD 1.66 g/L, 95% CI 0.26 to 3.05). Significantly more patients experienced adverse events in the cyclosporin A group than in the placebo group, especially renal dysfunction (Peto odds ratio 5.56, 95% CI 2.52 to 12.27) and hypertension (SMD 0.88, 95% CI 0.27 to 1.48). AUTHORS' CONCLUSIONS: We found no evidence supporting or refuting that cyclosporin A may delay death, death or liver transplantation, or progression of primary biliary cirrhosis. Cyclosporin A caused more adverse events than placebo, like renal dysfunction and hypertension. We do not recommend the use of cyclosporin A outside randomised clinical trials.