Treatment with the purine synthesis inhibitor mizoribine for ANCA-associated renal vasculitis

Background: The common treatment for antineutrophil cytoplasmic autoantibody (ANCA)-associated renal vasculitis is oral cyclophosphamide (CYC)-corticosteroid combination therapy. However, there are serious complications associated with long-term use of CYC. In this study, we investigate the efficacy of a purine synthesis inhibitor, mizoribine, for patients at high risk for relapse. Methods: Our study included 5 patients, 4 patients with myeloperoxidase (MPO)-ANCA-associated renal vasculitis and 1 patient with proteinase 3 (PR3)-ANCA-associated renal vasculitis, who had achieved remission through treatment with methylprednisolone pulse therapy, corticosteroids, and CYC. When their ANCA titers were found to be greater than normal range after remission status, mizoribine treatment was initiated. Results: Median time from initial treatment to first administration of mizoribine was 40.0 months (range, 24 to 51 months). Median follow-up was 13.0 months (range, 6 to 16 months). Before initiation of mizoribine treatment, no patient had experienced relapse and ANCA titers were less than the detectable range in all patients at 3 months before mizoribine administration. When mizoribine administration was started, ANCA titers were elevated in all patients (median MPO-ANCA, 101 ELISA units [EU]; range, 65 to 154 EU; PR3-ANCA, 55 EU), but no new symptoms or signs of relapse were noted. After 2 months of mizoribine treatment, only 1 patient had experienced a relapse; however, ANCA titers had decreased in all other patients and normalized in 3 patients. No adverse effects appeared in any patient. Conclusion: Considering the balance between suppression of disease activity and adverse effects of treatment, mizoribine may be useful for preemptive treatment for patients with ANCA-associated renal vasculitis at high risk for relapse.