Use of 6-Mercaptopurine in Autoimmune Hepatitis Patients Intolerant to Azathioprine

Summary and Comment |
March 23, 2016

Use of 6-Mercaptopurine in Autoimmune Hepatitis Patients Intolerant to Azathioprine

  1. Atif Zaman, MD, MPH

This second-line treatment strategy shows promise.

  1. Atif Zaman, MD, MPH

Approximately 10% of patients with autoimmune hepatitis (AIH) do not respond to treatment with azathioprine (AZA) or are intolerant of it. Although effective second-line agents exist (e.g., mycophenolate mofetil), some require drug-level monitoring, are expensive, or have significant adverse effects. Although AZA is a prodrug of 6-mercaptopurine (6-MP), AZA intolerance does not necessarily lead to 6-MP intolerance.

Researchers retrospectively investigated response and tolerance to 6-MP in 22 patients (18 women; median age, 53 years) with AIH who had inadequate response or developed AZA intolerance and were switched to 6-MP. AZA was replaced with 6-MP starting at a dose of 25 mg/day and increased to ≥50 mg/day or more if tolerated. Complete therapeutic response was defined as normalization of liver enzymes, immunoglobulin G, and gamma-globulins, and partial response was defined as reduction in these parameters to less than twice the upper limit of normal. Therapeutic response was assessed after 4 weeks of treatment.

Among the 20 patients with AZA intolerance, 15 responded to treatment with 6-MP. Complete response occurred in 8 patients and partial response in 7 patients. The other 5 patients developed intolerance to 6-MP and required an alternative regimen. The 2 patients with inadequate response to AZA did not show response to 6-MP.

Comment

In this small patient series, the majority of AIH patients who had intolerance to AZA therapy were successfully switched to 6-MP. Also, patients with inadequate response to AZA also had inadequate response to 6-MP — an observation consistent with the fact that these two agents are metabolically similar. Based on these results, a reasonable approach to treating AZA-intolerant patients with AIH is to first consider a switch to 6-MP before prescribing more-expensive second-line agents such as mycophenolate mofetil.

Editor Disclosures at Time of Publication

  • Disclosures for Atif Zaman, MD, MPH at time of publication Nothing to disclose

Citation(s):

Reader Comments (1)

HAMED ALKAFF Physician, Gastroenterology, Sana'a University Hospital, Sana'a, Yemen

Good alternative

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