Tacrolimus Versus Mycophenolate for Autoimmune Hepatitis Patients With Incomplete Response on First Line Therapy
Status:
Recruiting
Trial end date:
2024-01-01
Target enrollment:
Participant gender:
Summary
Rationale: The combination of azathioprine and prednisone is the first-line treatment for
autoimmune hepatitis (AIH), a chronic inflammatory disease of the liver. Complete biochemical
remission (CR) is the first treatment goal in autoimmune hepatitis. CR is determined by AST
and ALT and IgG within the reference range. CR is not reached in a substantial proportion of
AIH patients: after one year 50%, after three years around 20% did not achieve CR. Without CR
ongoing hepatitis leads to progression towards fibrosis and eventually (decompensated)
cirrhosis. Not achieving CR is the most important risk factor for the need for liver
transplantation or liver related death, independent of age and presence of cirrhosis.
Tacrolimus (TAC) and mycophenolate mofetil (MMF) are frequently used to prevent rejection in
kidney and liver transplant patients. In AIH patients with insufficient response or
intolerance to first-line therapy in retrospective cohort studies with MMF 0-57% and with TAC
20-95% CR was reached.
Objective: The aim of this study is to compare the effectiveness of TAC with MMF as a second
line treatment for AIH. Proportion of patients with CR after 12 months of treatment will be
the primary outcome parameter to determine effectivity.
Study design: Randomized open-label two arm study. Patients will be randomized between
treatment with TAC or MMF.
Study population: Patients with AIH with an incomplete response (no CR) to first-line
treatment are eligible for this study.
Intervention: In the TAC group baseline treatment will be replaced by tacrolimus. In the MMF
group baseline treatment will be replaced by MMF. The current dose of prednisolone, or at
least 5 mg daily, will be continued in both arms. After achieving CR prednisolone will be
tapered according to protocol.
Main study parameters/endpoints: Difference in proportion of patients with CR at 12 months
(normalization of ALT, AST and IgG) between the TAC and MMF treatment group.
Secondary parameters:
- Safety and tolerability of TAC and MMF treatments
- Difference in proportion of patients with CR at 6 months (normalization of ALT, AST and
IgG) between the TAC and MMF treatment group.
- Difference in ALT, AST and IgG at 6 and 12 months versus baseline
- Difference in fibrogenesis and fibrosis parameters between groups and before and after
treatment
- Difference in quality of life between groups and before and after treatment