What is the role of azathioprine in the remission maintenance of granulomatosis with polyangiitis (GPA)?

Updated: Aug 31, 2021
  • Author: Christopher L Tracy, MD; Chief Editor: Herbert S Diamond, MD  more...
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Answer

Azathioprine has been proven inferior to cyclophosphamide during the induction phase of treatment. However, as shown by the CYCAZAREM (Cyclophosphamide Versus Azathioprine During Remission in ANCA-Associated Vasculitis) trial, azathioprine (2 mg/kg/day) is safer and as effective as cyclophosphamide in maintaining remission. [8] Azathioprine impairs leukocyte proliferation by inhibiting purine synthesis. It results in somewhat higher relapse rates than cyclophosphamide, especially if the patient is still PR3-ANCA–positive at the time of the switch from cyclophosphamide to azathioprine. [8, 80, 81]

Study data have raised the question as to whether the induction treatment phase can be shortened to 3 months with transition from cyclophosphamide to azathioprine. The European Vasculitis Study Group analyzed a group of 144 patients with ANCA-associated vasculitis (GPA and microscopic polyangiitis) who achieved remission with induction therapy of prednisolone and cyclophosphamide (2 mg/kg/day) for 3 months.

After a 3-month induction phase, patients were randomized to cyclophosphamide (1.5 mg/kg/day) or azathioprine (2 mg/kg/day). Remission rates and adverse effects were similar in both groups. The authors concluded that once remission is achieved with a 3-month course of prednisolone and cyclophosphamide, patients can be safely switched from cyclophosphamide to azathioprine to reduce the exposure to cyclophosphamide.


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