Dr Burton Combes and colleagues compared the effects of combination therapy on the course of primary biliary cirrhosis.
The research team assessed the effects of methotrexate plus ursodeoxycholic acid to ursodeoxycholic acid alone.
The team conducted a placebo-controlled, randomized, multicenter trial.
The researchers stratified 265 AMA positive patients according to Ludwig's histological staging.
The patients presented without ascites, variceal bleeding, or encephalopathy.
The team reported that the patients had a serum bilirubin less than 3 mg/dL, serum albumin 3 g/dL or greater.
The patients had also taken ursodeoxycholic acid 15 mg/kg daily for at least 6 months.
|Occurrence of treatment failures with ursodeoxycholic acid plus methotrexate vs single treatment did not differ|
The researchers randomized the patients to methotrexate 15 mg/m2 body surface area once a week while continuing on ursodeoxycholic acid.
The median time from randomization to closure of the study was 7 years.
Treatment failure was defined as death without liver transplantation, transplantation, variceal bleeding, and development of ascites.
The researchers also included encephalopathy, or varices, a doubling of serum bilirubin to 2.5 mg/dL or greater as definitions of treatment failure.
A fall in serum albumin to 2.5 g/dL or less, and histological progression by at least 2 stages or to cirrhosis was included in the definition of treatment failure.
The team continued patients on treatment despite failure of treatment, unless transplantation ensued.
If drug toxicity necessitated withdrawal, or the patient developed a cancer, treatment was discontinued.
The researchers found no significant differences in these parameters.
No differences were observed in the time of development of treatment failures with ursodeoxycholic acid plus methotrexate, or ursodeoxycholic acid plus placebo.
The research team conducted the trial with a stopping rule.
The team reported that the trial was stopped early by the National Institutes of Health at the advice of the Data Safety Monitoring Board for reasons of futility.
Dr Combes' team concludes, “Methotrexate when added to ursodeoxycholic acid for a median period of 7 years had no effect on the course of primary biliary cirrhosis treated with ursodeoxycholic acid alone.”