Abstract | BACKGROUND & AIMS: 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.
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Authors | Jayant A Talwalkar, Paul Angulo, Jill C Keach, Janice L Petz, Roberta A Jorgensen, Keith D Lindor |
Journal | Journal of clinical gastroenterology
(J Clin Gastroenterol)
Vol. 39
Issue 2
Pg. 168-71
(Feb 2005)
ISSN: 0192-0790 [Print] United States |
PMID | 15681915
(Publication Type: Clinical Trial, Clinical Trial, Phase II, Comparative Study, Journal Article)
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Chemical References |
- Autoantibodies
- Cholagogues and Choleretics
- Immunosuppressive Agents
- Ursodeoxycholic Acid
- Alkaline Phosphatase
- Mycophenolic Acid
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Topics |
- Administration, Oral
- Adolescent
- Adult
- Aged
- Alkaline Phosphatase
(blood)
- Autoantibodies
(blood)
- Cholagogues and Choleretics
(administration & dosage, therapeutic use)
- Dose-Response Relationship, Drug
- Drug Therapy, Combination
- Female
- Follow-Up Studies
- Humans
- Immunosuppressive Agents
(administration & dosage, therapeutic use)
- Liver Cirrhosis, Biliary
(blood, drug therapy, pathology)
- Male
- Middle Aged
- Mitochondria, Liver
(immunology)
- Mycophenolic Acid
(administration & dosage, analogs & derivatives, therapeutic use)
- Pilot Projects
- Risk Factors
- Treatment Outcome
- Ursodeoxycholic Acid
(administration & dosage, therapeutic use)
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