ABSTRACT FINAL ID: 1650
TITLE: Mycophenolate Mofetil in Autoimmune Hepatitis Patients not Responsive or Intolerant to Standard Therapy: the Australian TAPESTRY study
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Conventional therapy of autoimmune hepatitis (AIH) is with corticosteroids with or without azathioprine. However 20% of patients do not respond or are intolerant to standard therapy. Thus, we evaluated the efficacy and safety of mycophenolate mofetil (MMF) in AIH patients who had failed or were intolerant to corticosteroids with or without azathioprine.
A retrospective study was performed of AIH patients who received MMF alone or in combination with prednisolone after failure or intolerance of standard therapy. Patients were recruited from 16 liver clinics across Australia via the ALA Clinical Research Network. Records were reviewed for baseline demographics and liver disease characteristics, initial therapy, indications for MMF initiation, treatment outcome and complications.
A total of 96 patients (mean age 45.3 yrs, females 86.5%, Caucasian 53%, cirrhosis 19.8%) received treatment with MMF for AIH across the 16 centres including 95 in combination with corticosteroids. The majority (73%) had received prior combination therapy with corticosteroids plus azathioprine/6-mercaptopurine. The indication for MMF was non-response in 43% and intolerance to standard therapy in 53%. The median starting and maximal doses of MMF received was 1gm/d and 2gm/d respectively; the median treatment duration was 31.9 months. Overall, 44 (45.9%) patients achieved biochemical remission on MMF after a median treatment duration of 11 weeks, 8 (18%) of whom relapsed during follow up. Of the 40 patients treated for non-response, 17 (42.5%) achieved biochemical remission after a median of 12 weeks, while 8 (20%) had an incomplete response and 3 (7.5%) had treatment failure. Of the 49 patients receiving MMF for intolerance/toxicity, 27 (55%) achieved remission, with 4 (8%) having an incomplete response and 1 (2%) treatment failure. 8 patients required dose-reduction and 16 discontinued MMF mainly due to lack of efficacy (n=6) or intolerance (n=6). Serious adverse events occurred in 3 patients (1 death, 2 hospitalisations), while there were 23 significant complications including GI toxicity (n=8), infection (n=5), cytopenias (n=3), neuropsychiatric (n=3), skin cancer (n=2), and lymphoproliferative disorder (n=1).
Treatment with MMF combined with corticosteroids in AIH patients who fail to respond or are intolerant to standard therapy is moderately effective achieving an overall remission rate of around 50% including 43% in non-responders to standard therapy. MMF appears relatively safe and well tolerated with the main side-effects being GI toxicity, infection, and cytopenias.