Cyclosporin A for primary biliary cirrhosis.
BACKGROUND
Cyclosporin A has been used for patients with primary biliary cirrhosis, but the therapeutic responses in randomised clinical trials have been heterogeneous.


OBJECTIVE
To assess the beneficial and harmful effects of cyclosporin A for patients with primary biliary cirrhosis.


METHODS
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.


METHODS
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.


METHODS
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.


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).


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.
Gong
Y
Y
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Cochrane Hepato-Biliary Group, Rigshospitalet, Dept. 3344, Blegdamsvej 9, Copenhagen, DENMARK, DK-2100. ygong@ctu.rh.dk
Christensen
E
E
Gluud
C
C
D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D007166:Immunosuppressive Agents; D016572:Cyclosporine