title: Methotrexate in patients with primary biliary cirrhosis who respond incompletely to treatment with ursodeoxycholic acid.
abstract: BACKGROUND
  Approximately 35% of PBC patients have progressive disease despite treatment with UDCA.
  
  
  OBJECTIVE
  We offered treatment with methotrexate and colchicine to PBC patients who had not responded fully to UDCA, after at least 1 year of treatment.
  
  
  METHODS
  A total of 91 PBC patients failed to respond adequately to UDCA, defined as patients whose liver biopsies showed persistent interface hepatitis and whose serum alkaline phosphatase levels remained more than 50% above normal after at least 12 months on UDCA. We added colchicine (0.6 mg orally twice daily) for 6 months. If there was no decrease in alkaline phosphatase, methotrexate (0.25 mg/kg lean body weight orally per week) was added. Liver biopsies were performed at least three times: at diagnosis, after a patient had been on UDCA for at least 1 year (mean 3.4 years), and after a patient had been on methotrexate for at least 6 months (mean 2.2 years). A fourth liver biopsy was performed in 51 patients after they had been on methotrexate for at least another year (mean 3.5 years).
  
  
  RESULTS
  From the time that methotrexate was begun until the final visit, there were significant decreases in the mean levels of alkaline phosphatase, 323 to 151, ALT, 73 to 39, fibrosis, 2.5 to 2.0, and inflammation scores, 2.0 to 1.0, (p < 0.0001 for all). Based on pre-specified definitions, 73 patients (80%) responded to methotrexate while 18 (20%) did not.
  
  
  CONCLUSIONS
  In 91 PBC patients who responded incompletely to UDCA, colchicine and methotrexate significantly improved liver enzyme tests and liver histology.
authors.affiliation: Division of Gastroenterology, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA. mkaplan@tuftsmedicalcenter.org
authors.forename: Marshall M
authors.initials: MM
authors.lastname: Kaplan
authors.forename: Alan
authors.initials: A
authors.lastname: Bonder
authors.forename: Robin
authors.initials: R
authors.lastname: Ruthazer
authors.forename: Peter A L
authors.initials: PA
authors.lastname: Bonis
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D003078:Colchicine / Q000008:administration & dosage / Q000627:therapeutic use; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005355:Fibrosis; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008111:Liver Function Tests; D008727:Methotrexate / Q000627:therapeutic use*; D017211:Treatment Failure; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D002756:Cholagogues and Choleretics; D007166:Immunosuppressive Agents; D014580:Ursodeoxycholic Acid; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D001663:Bilirubin; D003078:Colchicine; D008727:Methotrexate