Mycophenolate mofetil trumps azathioprine for remission in treatment-naive autoimmune hepatitis

Treatment with mycophenolate mofetil (MMF) in combination with prednisolone results in better biochemical remission rates at 24 weeks than the use of azathioprine plus prednisolone in patients with treatment-naïve autoimmune hepatitis (AIH), reports a study.

In addition, azathioprine use appears to produce more serious adverse events (AEs) that lead to treatment cessation, indicating the superior tolerability of MMF.

“Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events,” said lead author Romée J.A.L.M. Snijders, Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.

“The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis,” she added.

This randomized, open-label, multicentre superiority trial included 70 patients (mean age 57.9 years, 72.9 female) who received either MMF (n=39) or azathioprine (n=31), both combined with prednisolone. Biochemical remission, the primary endpoint, was defined as normalization of serum levels of alanine aminotransferase and IgG after 24 weeks. Safety and tolerability were secondary endpoints.

More patients in the MMF than in the azathioprine group achieved the primary endpoint (56.4 percent vs 29.0 percent; difference, 27.4 percentage points, 95 percent confidence interval [CI], 4.0‒46.7; p=0.022). Biochemical response rates at 6 months were also greater in the MMF group (72.2 percent vs 32.3 percent; p=0.004). [J Hepatol 2024;80:576-585]

Four serious AEs occurred in the azathioprine group and none in the MMF group (12.9 percent vs 0 percent; p=0.034). Two patients who received MMF and eight who received azathioprine ceased treatment due to AEs or serious AEs (5.1 percent vs 25.8 percent; p=0.018).

“These outcomes provide a potential basis to inform international guidelines regarding the standard of care in patients with treatment-naive AIH,” Snijders said.

First-line therapy

These findings also support those of Dalekos and colleagues. [Front Immunol 2021;12798602; JHEP Rep 2022;4100601]

“Based on these results, the Hellenic Association for the Study of the Liver (HASL) recommends that MMF may be considered as a first-line therapy option, particularly within specialized AIH centres,” the authors said. [Ann Gastroenterol 2019;32:1-23]

One of Dalekos’ studies reported no significant difference in response rates at 6 months. On the other hand, a meta-analysis revealed significantly higher response rates with MMF plus prednisolone compared with standard treatment. [Eur J Gastroenterol Hepatol 2019;31:873-877]

Notably, Snijders and her team stressed that MMF has high teratogenicity and must not be used during pregnancy. On the other hand, azathioprine is safe to use during pregnancy.

“It is worth considering creating a two-tier treatment algorithm specifically for patients at a fertile age,” the authors said.

The present study did not perform a cost-effectiveness analysis due to insufficient data on additional incidental and structural healthcare costs.

“It remains essential to undertake further research involving novel immunomodulatory or immunosuppressive agents to enhance treatment strategies in AIH,” the authors said.