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Intervention Review

Methotrexate for primary biliary cirrhosis

  1. Yan Gong1,*,
  2. Christian Gluud2

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 20 JUL 2005

Assessed as up-to-date: 13 MAR 2005

DOI: 10.1002/14651858.CD004385.pub2


How to Cite

Gong Y, Gluud C. Methotrexate for primary biliary cirrhosis. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD004385. DOI: 10.1002/14651858.CD004385.pub2.

Author Information

  1. 1

    Copenhagen NV, Denmark

  2. 2

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Cochrane Hepato-Biliary Group, Copenhagen, Denmark

*Yan Gong, Bispeberg Bakke 26C, 2.th, Copenhagen NV, 2400, Denmark. gong_yan2002@yahoo.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 20 JUL 2005

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This is not the most recent version of the article. View current version (12 MAY 2010)

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary

Background

Methotrexate, a folic acid antagonist with immunosuppressive properties, has been used to treat patients with primary biliary cirrhosis. The therapeutic responses to methotrexate in randomised clinical trials have been heterogeneous.

Objectives

To assess the beneficial and harmful effects of methotrexate for patients with primary biliary cirrhosis.

Search strategy

Relevant randomised clinical trials were identified by searching The Cochrane Hepato-Biliary Group Controlled Trials Register (June 2004), The Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 2, 2004), MEDLINE (January 1966 to August 2004), EMBASE (January 1980 to August 2004), and manual searches of bibliographies. We contacted authors of trials and pharmaceutical companies.

Selection criteria

Randomised clinical trials comparing methotrexate 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 hazard ratio (HR) if applicable. Continuous outcomes were reported as weighted mean difference (WMD). We examined intervention effects by using both a random-effects model and a fixed-effect model. Heterogeneity was investigated by subgroup analyses and sensitivity analyses.

Main results

We identified four trials (370 patients) that compared methotrexate with placebo with or without ursodeoxycholic acid as co-intervention. One additional trial (87 patients) compared methotrexate with colchicine without and later with ursodeoxycholic acid as co-intervention. The methodological quality of the trials was low. We did not find significant effects of methotrexate on pruritus, fatigue, liver complications, liver biochemistry, liver histology, or adverse events. The pruritus score (WMD - 0.68, 95% CI - 1.11 to - 0.25), the levels of serum alkaline phosphatases (WMD - 0.41, 95% CI - 0.70 to - 0.12) and plasma immunoglobulin M (WMD - 0.47, 95% CI - 0.74 to - 0.20) were significantly lower in the patients receiving methotrexate.

Authors' conclusions

Methotrexate increased mortality in patients with primary biliary cirrhosis. We do not recommend methotrexate for patients with primary biliary cirrhosis outside randomised trials.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary

Methotrexate tend to increase mortality or liver transplantation in patients with primary biliary cirrhosis

Primary biliary cirrhosis is an uncommon chronic liver disease of unknown etiology. Methotrexate, a folic acid antagonist with immunosuppressive properties, has been used to treat patients with primary biliary cirrhosis. However, methotrexate may increase the risk of mortality or the number of patients in need of liver transplantation. The effects of methotrexate on pruritus, fatigue, clinical complications, liver biochemistry levels, liver histology, and adverse events were not significantly different from placebo.