A prospective, randomized-controlled pilot study of ursodeoxycholic acid combined with mycophenolate mofetil in the treatment of primary sclerosing cholangitis.
BACKGROUND
Ursodeoxycholic acid has been ineffective in the treatment of primary sclerosing cholangitis. Because the pathogenesis of primary sclerosing cholangitis is related to immune destruction of bile duct epithelium, several immune suppressive agents have been evaluated. Mycophenolate mofetil is a potent immunosuppressant that is now widely used in organ transplantation.


OBJECTIVE
In this pilot study to determine if mycophenolate mofetil when combined with ursodeoxycholic acid could prevent evidence of clinical progression and improve the biochemical, histological and/or cholangiographic features of primary sclerosing cholangitis compared with patients treated with ursodeoxycholic acid alone.


METHODS
Twenty-five patients with well-defined primary sclerosing cholangitis were randomized to ursodeoxycholic acid (13-15 mg/kg/day) with or without mycophenolate mofetil (1000 mg b.d.). Cholangiography and liver biopsy were performed at study entry and after 2 years of treatment. Symptoms, clinical features of liver disease and biochemical tests were monitored at 3-month intervals.


RESULTS
The mean age 44 years, 58% male, 84% Caucasian and 64% had ulcerative colitis. After 2 years, there were no differences in laboratory values, histological stage or cholangiograms between patients treated with ursodeoxycholic acid alone and those treated with mycophenolate mofetil + ursodeoxycholic acid.


CONCLUSIONS
Mycophenolate mofetil combined with ursodeoxycholic acid does not appear to provide additional benefit compared with standard doses of ursodeoxycholic acid alone in the treatment of primary sclerosing cholangitis.
Sterling
R K
RK
Division of Gastroenterology and Hepatology, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA. rksterli@hsc.vcu.edu
Salvatori
J J
JJ
Luketic
V A
VA
Sanyal
A J
AJ
Fulcher
A S
AS
Stravitz
R T
RT
Contos
M J
MJ
Mills
A S
AS
Shiffman
M L
ML
D000328:Adult; D001706:Biopsy / Q000379:methods; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D015209:Cholangitis, Sclerosing / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010865:Pilot Projects; D011446:Prospective Studies; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D007166:Immunosuppressive Agents; D014580:Ursodeoxycholic Acid; D009173:Mycophenolic Acid