Combined treatment with methotrexate and ursodeoxycholic acid in non-cirrhotic primary biliary cirrhosis

In the treatment of patients with primary biliary cirrhosis (PBC), methotrexate (MTX) and ursodeoxycholic acid (UDCA) have both been associated with clinical, biochemical, and histologic improvement. Studies with methotrexate have only been performed in uncontrolled conditions. We conducted a prospective controlled study on the combined treatment with methotrexate and ursodeoxycholic acid, comparing the clinical, biochemical, and histologic evolution in six untreated patients with that in eight patients treated with MTX 15 mg/week in association with UDCA 500 mg/day. All patients had noncirrhotic PBC and were followed up for two years. A significant decrease of alkaline phosphatase, glutamic pyruvic transaminase, and gamma-glutamyltranspeptidase was found in the methotrexate/ursodeoxycholic acid treated-group, as compared to the control group. The clinical and histologic evolution, however, was not significantly different in the two groups. Methotrexate toxicity consisted of interstitial pneumonitis in one, of a transient rise of transaminases at three months in five, and of a significant decrease of blood platelets and white blood cells after two years of treatment. In controlled conditions, a two-year treatment with methotrexate and ursodeoxycholic acid does not produce a significant clinical or histologic benefit. Based on this experience, and taking into account the possible risks associated with this therapy, the empiric use of methotrexate cannot be recommended in patients with non-cirrhotic PBC.