THE COMBINATION OF URSODEOXYCHOLIC ACID AND METHOTREXATE PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS - THE RESULTS OF A PILOT-STUDY

Ursodeoxycholic acid (UDCA) and methotrexate (MTX) have both been prop osed as treatments for patients with primary biliary cirrhosis (PBC). It has been suggested that a combination of the two drugs may offer ad vantages over either used separately. In this pilot study, we sought t o evaluate the safety and efficacy of this combination for patients wi th PBC. Thirty-two patients with antimitochondrial antibody positive P BC were prospectively entered into a pilot study and received UDCA, 13 to 15 mg/kg/d, in conjunction with MTX, 0.25 mg/kg/wk, for a period o f 2 years. The results of this treatment were compared with those obta ined from 180 patients with PBC studied in a placebo-controlled trial of UDCA alone conducted during the same period. Patients in the pilot study and randomized study were comparable with regard to age, gender, and liver biochemistries. The UDCA/MTX-treated patients were of earli er histologic stage and had a lower mean Mayo risk score. During this period, seven patients in the UDCA/MTX group were withdrawn, four for pulmonary toxicity (two who required hospitalization), and one each wi th mouth ulcer, extreme fatigue, and hair loss. The use of UDCA/MTX wa s not associated with improvement in symptoms. In the patients receivi ng UDCA/MTX, biochemical changes were comparable to those of patients receiving UDCA alone but superior to those in the placebo group (P < . 05). Histological changes were comparable in all groups at 2 years. Ce ssation of MTX while UDCA was continued led to no deterioration in liv er biochemistries. In a 2-year study, the use of MTX in combination wi th UDCA was associated with substantial toxicity, but with no evidence for symptomatic, biochemical, or histologic improvement over that see n with UDCA alone. The use of MTX in patients with PBC should be confi ned to patients in prospective trials and not used on an empiric basis .