Mycophenolate mofetil for the treatment of primary biliary cirrhosis in patients with an incomplete response to ursodeoxycholic acid.
OBJECTIVE
Despite evidence for therapeutic efficacy with ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC), only 30-50% of patients achieve complete biochemical remission within 1 year of therapy. Mycophenolate mofetil (MMF) is an immunosuppressive medication that inhibits T and B lymphocyte proliferation. The aim of this investigation was to determine the safety and estimated efficacy of MMF in patients with PBC.


METHODS
Twenty-five patients with incomplete responses to UDCA (defined as persistent elevation of serum alkaline phosphatase > or =2 times the upper limit of normal) received MMF 1 g daily to a maximum of 3 g daily with UDCA (13-15 mg/kg per day) for 1 year. Liver biochemistries were determined at 3-month intervals with Mayo Risk Score calculated at baseline and end of therapy.


RESULTS
Nineteen (76%) patients completed 1 year of therapy. Despite improvements in serum alkaline phosphatase (920 +/- 308 vs. 709 +/- 242 IU/L, P = 0.001) and AST (65 +/- 31 vs. 51 +/- 19 IU/L, P = 0.007) levels, these findings were clinically insignificant. Exploratory analysis revealed a strong correlation between advanced PBC defined by higher Mayo Risk Score and reduction in serum alkaline phosphatase levels (r = -0.74, P = 0.006). Six patients (24%) did not complete therapy; adverse drug events were responsible for study withdrawal in 3 individuals. Adverse reactions that resolved spontaneously or by dose reduction occurred in 13 patients.


CONCLUSIONS
MMF is not associated with important clinical benefits in PBC based on the results of this pilot investigation.
Talwalkar
Jayant A
JA
Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. talwalkar.jayant@mayo.edu
Angulo
Paul
P
Keach
Jill C
JC
Petz
Janice L
JL
Jorgensen
Roberta A
RA
Lindor
Keith D
KD
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000276:immunology; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010865:Pilot Projects; D012307:Risk Factors; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use*
D001323:Autoantibodies; D002756:Cholagogues and Choleretics; D007166:Immunosuppressive Agents; D014580:Ursodeoxycholic Acid; D000469:Alkaline Phosphatase; D009173:Mycophenolic Acid