6-Mercaptopurine vs. Mycophenolate Mofetil in Autoimmune Hepatitis and Azathioprine Intolerance: A Multicenter Study

Abstract

Background & aims: Azathioprine (AZA) and corticosteroids are the recommended standard therapy for autoimmune hepatitis (AIH); however, a significant proportion of patients discontinue AZA due to intolerance. Although guidelines propose 6-mercaptopurine (6-MP) and mycophenolate mofetil (MMF) as alternatives, there is a lack of data on 6-MP and no comparative studies in AIH. We aimed to compare the efficacy and safety of 6-MP and MMF as second-line therapies in patients intolerant to AZA.

Methods: This multicenter retrospective cohort study involved AIH patients from eleven tertiary care centers across Europe and Canada who were intolerant to AZA and subsequently switched to either 6-MP or MMF as second-line interventions. Data on biochemical response, adverse effects, and treatment duration of second-line therapies were collected and analyzed, incorporating propensity score matching to validate the biochemical response.

Results: We included 211 AIH patients (81% female; median age: 54 years (IQR: 39-63 years)) with a median follow-up of 60 months (IQR: 31-105 months). MMF was better tolerated than 6-MP (89% vs. 67%; p < 0.001). Among patients who continued second-line treatment, no statistically significant difference in complete biochemical response rates was observed between 6-MP and MMF (61% and 66%, respectively, at the last follow-up).

Conclusions: Both 6-MP and MMF were capable of maintaining biochemical response in patients with AIH who were intolerant to AZA, with no clear evidence of inferiority of either treatment. While MMF was generally better tolerated, 6-MP may present a safe and effective treatment option in women of reproductive age. In addition, therapy with 6-MP enables clinicians to monitor drug metabolite levels, titrate dosages, and monitor adherence.

Keywords: AIH; Azathioprine intolerance; Immunosuppression; Second-line therapy.