title: Mycophenolate mofetil for the treatment of primary sclerosing cholangitis.
abstract: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology. Despite advances in understanding the pathophysiology underlying this disorder, no effective medical therapy has been identified for halting disease progression. The aim of this investigation was to determine the safety and estimated efficacy of mycophenolate mofetil (MMF) for the treatment of PSC. Thirty patients with PSC received MMF 1 g daily to a maximum of 3 g daily for 1 yr. Liver tests were determined at 3-month intervals with the Mayo risk score calculated at baseline and at the end of therapy. Twenty-three (77%) patients completed 1 yr of therapy. Significant but clinically marginal improvement in serum alkaline phosphatase level after 1 yr of therapy was observed (1135 +/- 581 U/L vs 912 +/- 463 U/L, p= 0.02). No other significant changes in liver biochemistries or Mayo risk score was observed. Seven patients (23%) discontinued MMF due to adverse events possibly related to therapy. Adverse reactions resolved spontaneously or with dose reduction in 10 (33%) patients. One patient developed pancreatitis, bacterial cholangitis, and sepsis during the eighth month of MMF therapy. No patient developed cytopenia on therapy. In conclusion, MMF does not appear to have clinically important benefits for PSC despite being tolerated by most patients. The results of this pilot study do not support further study of MMF as a single agent in the treatment of PSC.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, 200 SW First Street, Rochester, MN 55905, USA.
authors.forename: Jayant A
authors.initials: JA
authors.lastname: Talwalkar
authors.forename: Paul
authors.initials: P
authors.lastname: Angulo
authors.forename: Jill C
authors.initials: JC
authors.lastname: Keach
authors.forename: Janice L
authors.initials: JL
authors.lastname: Petz
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Jorgensen
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lindor
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015209:Cholangitis, Sclerosing / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010865:Pilot Projects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D009173:Mycophenolic Acid; D001663:Bilirubin