Lindor- PBC Mortality Risk

[Guest guest]

Center

for the Advancement of Health

Date:

2005-08-24

Treatment

For Rare Liver Disease Increases Mortality Risk

Patients with primary

biliary cirrhosis who are treated with methotrexate

have an increased risk of death, according to a new

systematic review of studies.

In five randomized controlled trials involving

457 people, the authors report that for patients treated with methotrexate, as a single therapy or in combination with other

drug treatment, pooled data showed a tendency toward an increased risk of death

or liver transplantation. The brand names for methotrexate

are Rheumatrex and Trexall.

“ We do not advocate the use

of methotrexate for patients with primary biliary

cirrhosis,” conclude lead investigator Yan

Gong, M.D., of Copenhagen University

Hospital in Denmark

and colleagues.

Their review appears in the latest issue of The Cochrane Library, a publication

of the Cochrane Collaboration, an international organization that evaluates

medical research. Systematic reviews draw evidence based conclusions about

medical practice after considering both the content and quality of existing

medical trials on a topic.

The reviewers

highlight the mortality and liver transplantation data from one long-term trial

in which 11 of 30 patients in the methotrexate group

died or underwent liver transplantation, compared with 7 of 30 patients in the

placebo group. Combining data from this and another trial other showed that

“…methotrexate had a significantly

detrimental effect on mortality.”

Methotrexate works by blocking

metabolism of cells and is effective in treating certain diseases characterized

by abnormal cell growth, like breast cancer and psoriasis. Methotrexate

is also widely used to treat rheumatoid arthritis.

Many

drugs have been used to treat primary biliary cirrhosis, with ursodeoxycholic acid (a bile acid) the most frequently

used. In contrast to methotrexate, the reviewers note

that they saw no “significant effect of ursodeoxycholic

acid on mortality or liver transplantation.”

Three of

the trials compared the therapeutic use of ursodeoxycholic

acid with and without methotrexate. One trial

compared methotrexate to colchicine.

Primary

biliary cirrhosis is an uncommon liver disease, and its cause is unknown,

although it may be an autoimmune disease. Ninety percent of patients are women

and most are diagnosed after the age of 40. It can be a precursor to cirrhosis

of the liver or liver failure.

Studies

over the past 30 years indicate an increasing prevalence of the disease, but

little progress has been made in slowing disease progression. Primary biliary

cirrhosis has become a frequent cause of liver morbidity, and patients with this

condition are increasingly undergoing liver transplantation.

The

Cochrane reviewers note that their conclusions could be qualified by the size

of the data pool and the mixed quality of the studies involved. “Although

the majority of the evidence did not point to a beneficial effect of methotrexate for patients with primary biliary

cirrhosis,” they write, “we were not able to exclude the

possibility for a beneficial effect in certain patient groups. We advise that

any new placebo-controlled trials with methotrexate

for patients with primary biliary cirrhosis should monitor harmful effects

closely.

Lindor, M.D., professor of medicine at the Mayo

Medical School,

says, “The most important finding in this review of the research is that methotrexate may indeed be harmful in the treatment of

primary biliary cirrhosis. The drug should not be used outside of clinical

trials, which will not likely be done with this drug because of the lack of

efficacy and potential harm.”

Gong Y, Gluud C. Methotrexate for primary

biliary cirrhosis. The Cochrane Database of Systematic Reviews 2005, Issue 3.

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