URSODEOXYCHOLIC ACID AND METHOTREXATE FOR PRIMARY SCLEROSING CHOLANGITIS - A PILOT-STUDY

Objective: Ursodeoxycholic acid (UDCA) and methotrexate (MTX) are both undergoing evaluation for the treatment of patients with primary scle rosing cholangitis (PSC). In this pilot study, we sought to study the safety and estimate of efficacy of a combination of these two drugs ad ministered over a 2-yr period in patients with PSC. Methods: Nineteen patients with well defined PSC were entered prospectively into a pilot study with anticipation of 2-yr follow-up. The patients received UDCA (13-15 mg/kg/day) in divided doses in conjunction with MTX (0.25 mg/k g/wk). The results of treatment were compared,vith a concurrently stud ied, but not randomized, group of 10 patients receiving UDCA alone. At entry, the two groups were comparable with respect to age, sex, liver biochemistries, and histological stage when available. Results: Durin g this period, five patients treated with the combination of UDCA and MTX were severed from the study (three referred for transplantation, o ne death from small bowel cancer, and one with pre-existing, high ileo stomy output who withdrew voluntarily). MTX was discontinued by the in vestigators in an additional five patients (hair loss in three, pulmon ary problems in two). There was no change in fatigue or itching compar ed,vith baseline in the group receiving the UDCA/MTX combination. Chan ges in biochemistries from baseline values were not different in the g roup receiving UDCA and MTX compared with the group receiving UDCA alo ne. Furthermore, after MTX was withdrawn and UDCA was continued, there was no clear evidence of further biochemical change. The use of MTX i n combination with UDCA was associated with toxicity without any furth er improvement in liver biochemistries compared with the use of UDCA a lone. Conclusion: This pilot study found no evidence to support the us e of MTX in combination with UDCA for patients with PSC.