A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten‐year results
Open accessAbstract
Primary biliary cirrhosis frequently progresses despite treatment with ursodeoxycholic acid (UDCA), the only approved therapy. Previous studies suggested that colchicine and methotrexate may improve biochemical tests of liver function, symptoms, and liver histology. The aim of the present study was to determine if the addition of colchicine or methotrexate to UDCA would improve survival free of liver transplantation. Eighty-five patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase levels were at least twice the normal level and who were not yet candidates for liver transplantation were randomly assigned to receive colchicine or methotrexate in a double-blind study. UDCA was administered to all patients after 2 years. The primary end point was survival free of liver transplantation. Patients were followed up for a total of up to 10 years or until treatment failure. Data were analyzed on an intention-to-treat basis. Transplant-free survival was similar in both groups: 0.57 for colchicine plus UDCA and 0.44 for methotrexate plus UDCA, results that are similar to those predicted by the Mayo prognostic model. Significant improvement in liver biochemical tests and liver histology was observed in a subset of patients in both treatment groups who remained in the study for all 10 years. In conclusion, neither colchcine plus UDCA nor methotrexate plus UDCA improved survival beyond that predicted by the Mayo prognostic model. However, clinical, histologic, and biochemical improvement observed among those who remained in the study for 10 years suggests a possible benefit of these drugs in a subset of patients. (Hepatology 2004;39:915-923.)
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- Authors
- Kaplan, M. M., Cheng, S., Price, L. L., & Bonis, P. A. L.
- Affiliations
- Tufts University (US)
- Corresponding author
- Kaplan, Marshall M.
- ORCID
- Price, Lori Lyn
- Venue
- Hepatology
- Published
- 2004-04
- Volume
- 39
- Issue
- 4
- Pages
- 915-923
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2005469957
- Cited by
- 87
- References
- 34
- Citations by year
- 2026: 1 · 2022: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 6 · 2016: 1 · 2015: 11 · 2014: 1 · 2013: 3 · 2012: 8
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK-34928, P30DK034928)
- National Center for Research Resources (RR00054, M01RR000054)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- primary biliary cirrhosis, colchicine, methotrexate, ursodeoxycholic acid, transplant-free survival, liver transplantation, liver histopathology, long-term treatment outcomes
- MeSH terms
- Anti-Inflammatory Agents, Cholagogues and Choleretics, Colchicine, Drug Therapy, Combination, Female, Gout Suppressants, Humans, Liver Cirrhosis, Biliary, Male, Methotrexate, Middle Aged, Referral and Consultation, Ursodeoxycholic Acid, Survival Analysis, Liver Transplantation, Treatment Outcome
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