By Craig Lammert, M.D., AIHA Executive Director
Azathioprine (Imuran) has reigned as the most common medication to treat autoimmune hepatitis (AIH) beyond steroids for more than 50 years. Yet, over the years, patients and doctors have raised concerns with its use. Reports have suggested up to 30% of patients have intolerance to azathioprine, and up to 30% of patients are not meeting treatment targets with azathioprine alone.
In the past few years, mycophenolate mofetil (also known as MMF or Cellcept) has emerged as a medication that may be better tolerated and even work better than azathioprine.
Data from European medical centers was recently published highlighting a randomized approach to AIH patients starting treatment. In this trial, 70 newly diagnosed AIH patients were treated with either azathioprine or MMF, both in combination with prednisolone.
The authors were particularly interested in the number of patients in each group that met the primary study endpoint, which was defined as normal alanine aminotransferase (ALT) and Immunoglobulin G (igG) levels after 24 weeks of treatment. They also carefully characterized the safety and tolerability of these medications.
What they found: The primary endpoint of normal ALT and IgG at 24 weeks was met in 56% of patients treated with MMF and only 29% of patients treated with azathioprine. There was no difference in the amount of prednisolone used, yet it is worth mentioning that 13% and 19% of patients being treated with MMF and azathioprine respectively were still using more than 5 mg of daily prednisolone therapy at 24 weeks. The researchers also found that drug-related adverse events were more prominent in the azathioprine-treated group compared to the MMF group (mostly nausea and vomiting:32% vs 8%).
This study is important for AIH patients for a few reasons:
- This study comes approximately 13 years after the last published treatment trial for AIH (budesonide vs prednisolone) – that’s a long time without new data guiding treatment in AIH.
- The number of individuals having normal liver tests at 24 weeks is still surprisingly low. This study shows that better treatments are needed that normalize liver tests in all patients because the inability to control inflammation can lead to the development of more liver fibrosis.
- A significant proportion of patients are requiring longer-term steroids to best control liver inflammation 6 months beyond diagnosis.
- Side effects of azathioprine were known previously, but this study nicely highlights how better tolerated MMF is.
This study leaves us with new information for AIH. Ultimately, it makes doctors have to think harder about first-line AIH treatment. This study does not definitively answer the question of “What is best: MMF or azathioprine?” rather it highlights another viable treatment option. Even though this study shows patients experiencing more side effects with azathioprine, MMF isn’t always the best choice.
One of MMF’s major drawbacks is its potential to cause birth defects in developing fetuses. Female patients who take MMF to control their AIH (and have potential to bear children) should utilize two forms of birth control while on the medication.
You can read more in the original article here.