Azathioprine versus mycophenolate mofetil in treatment-naive autoimmune hepatitis: 3-year follow-up of the CAMARO-trial.

BACKGROUND & AIMS: The CAMARO trial demonstrated superior short-term tolerability and response rates of mycophenolate mofetil (MMF) versus azathioprine (AZA), both combined with prednisolone, in treatment-naïve autoimmune hepatitis (AIH). We evaluated long-term outcomes.

METHODS

Patients enrolled in the multicenter randomized CAMARO trial were retrospectively followed for up to 3 years after treatment initiation. Co-primary endpoints were trial-assigned treatment with normalized alanine aminotransferase (ALT) at 3 years and time to biochemical response (normalization of ALT and immunoglobulin G).

RESULTS

Three-year follow-up was available for 67 patients (96%; 30 AZA, 37 MMF). At 3 years, 57% versus 76% remained on trial-assigned treatment with normalized ALT (p = 0.099). Median time to biochemical response was 64 versus 16 weeks (adjusted HR 2.74, 95% CI 1.49-5.06; p = 0.001). Among patients without ALT normalization at 24 weeks, 6/12 AZA-treated and 6/11 MMF-treated patients subsequently normalized ALT. Among patients remaining on randomized treatment at 24 weeks, subsequent treatment discontinuation occurred in 5/24 (21%) with AZA and 7/37 (19%) with MMF. Steroid-free ALT normalization (64% vs. 66%) and adverse event rates during year 3 (70% vs. 74%) were comparable (both p > 0.05). Five-year liver-related event-free survival was 70% (95% CI 55-93%) with AZA and 85% (95% CI 71-100%) with MMF (p = 0.080).

CONCLUSIONS

MMF was associated with faster biochemical response and numerically better overall tolerability. Among patients tolerating their assigned treatment during the initial treatment phase, subsequent outcomes were comparable between AZA and MMF. The substantial treatment burden with both therapies highlights the need for improved treatment options.

CLINICAL TRIAL NUMBER: NCT02900443.