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Dr. Kaplan gives us his thoughts on the following article
Methotrexate and transplantation
WESTPORT, Aug 30 (Reuters Health) - In patients with primary biliary cirrhosis, the risk of death or transplantation is increased nearly threefold with long-term use of low-dose methotrexate, according to the results of a 6-year, placebo-controlled study.
Dr. Mark T. Hendrickse and colleagues at Royal Hallamshire Hospital in Sheffield, England, studied the long-term effects of low-dose methotrexate, 7.5 mg/week, versus placebo in 60 patients with primary biliary cirrhosis.
Patients treated with methotrexate had significantly lower "...serum alkaline phosphatase, gamma-glutamyltransferase, [IgM], IgG, and (after 24 months) aspartate aminotransferase and alanine aminotransferase levels..." than controls. On the other hand, clinical factors, such as Knodell inflammatory scores and pruritus scores, were not significantly different between the two groups.
Moreover, patients randomized to low-dose methotrexate actually had an increased risk of death or liver transplantation, with a relative risk of 2.9, though this association did reach statistical significance.
The findings, published in the August issue of Gastroenterology, indicate that use of methotrexate in patients with primary biliary cirrhosis should be limited to the clinical trials setting, Dr. Hendrickse and colleagues conclude. They point out that higher doses of the drug may have enhanced efficacy in this population, but this was not tested in the current study.
Elsewhere in the journal, Drs. Paul Angulo and E. Rolland Dickson of the Mayo Clinic and Foundation in Rochester, Minnesota, point out the apparent dichotomy between the effects of low-dose methotrexate on biologic outcomes and clinically relevant outcomes in the British study. They suggest that the biologic markers studied may not be accurate predictors of disease status, a conclusion that is supported by other studies, as well.
The editorialists note that several promising drugs are currently in development for the treatment of primary biliary cirrhosis, but that ursodeoxycholic acid should remain the initial treatment for this disease until further data are available. The End.........
Dr. Kaplan's comments on this..........
Date: 9/10/99 8:46:01 AM Central Daylight Time
As you can see, this is a controversial area. The British investigators used approximately one half of the dose that I and others have found to be the minimally effective dose. A colleague and I have published a paper in the same issue of Gastroenterology that indicates that methotrexate improves blood tests and liver biopsy findings in patients who respond incompletely or not at all to ursodiol. I am in the tenth year of a doubleblind trial comparing methotrexate plus ursodiol to colchine plus ursodiol, but, because of the nature of the study, do not have any survival results yet. All that I can say is that methotrexate appears to be effective in my patients, but that I only use it in patients who have not responded fully to ursodioal or colchicine.
