Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis: the JMAAV study

Shoichi Ozaki,Hirofumi Makino,Manae S Kurokawa,Hidehiro Yamada,Akihiro Ishizu,Yasuyuki Kurihara,Tatsuya Atsumi,Taichi Hayashi,Shigeto Kobayashi,Yasuhiko Tomino,Hiroko Nagafuchi,Wako Yumura,Masaharu Yoshida,Kimimasa Nakabayashi,Shunichi Kumagai,Kunihiro Yamagata,Machi Suka,Norihiro Nishimoto

doi:10.1007/s10165-011-0525-5

Abstract

We (JMAAV [Japanese patients with MPO-ANCA-associated vasculitis] Study Group) performed a prospective, open-label, multi-center trial to evaluate the usefulness of severity-based treatment in Japanese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated vasculitis. Patients with MPO-ANCA-associated vasculitis received a severity-based regimen according to the appropriate protocol: low-dose corticosteroid and, if necessary, cyclophosphamide or azathioprine in patients with mild form; high-dose corticosteroid and cyclophosphamide in those with severe form; and the severe-form regimen plus plasmapheresis in those with the most severe form. We followed up the patients for 18 months. The primary end points were the induction of remission, death, and end-stage renal disease (ESRD). Fifty-two patients were registered, and 48 patients were enrolled in this study (mild form, n = 23; severe form, n = 23; most severe form, n = 2). Among the 47 patients who received the predefined therapies, 42 achieved remission within 6 months, 5 died, and 1 developed ESRD. Disease flared up in 8 of the 42 patients with remission during the 18-month follow-up period. The JMAAV trial is the first prospective trial for MPO-ANCA-associated vasculitis to be performed in Japan. The remission and death rates were comparable to those in several previous clinical trials performed in western counties. The regimen employed in this trial was tailor-made based on patients’ disease severity and disease type, and it seems that standardization can be consistent with treatment choices made according to severity.

Highlights

Among small-vessel vasculitides, microscopic polyangiitis (MPA), Wegener’s granulomatosis (WG), and allergic granulomatous angiitis (AGA) are known collectively as anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) because of the involvement of ANCA as the common pathogenesis [1]
We (JMAAV [Japanese patients with MPOANCA-associated vasculitis] Study Group) performed a prospective, open-label, multi-center trial to evaluate the usefulness of severity-based treatment in Japanese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated vasculitis
MPO-ANCA is related to MPA and AGA, and proteinase 3 (PR3)-ANCA is the marker antibody in WG [2, 3]

Summary

Introduction

Among small-vessel vasculitides, microscopic polyangiitis (MPA), Wegener’s granulomatosis (WG), and allergic granulomatous angiitis (AGA) are known collectively as anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) because of the involvement of ANCA as the common pathogenesis [1]. The major target antigens of ANCA associated with vasculitis are myeloperoxidase (MPO) and proteinase 3 (PR3). MPO-ANCA is related to MPA and AGA, and PR3-ANCA is the marker antibody in WG [2, 3]. MPO-ANCA-associated vasculitis is more common in Japan [4], whereas PR3-ANCA-associated vasculitis is more common in Europe and the United Staates. Untreated patients with severe AAV with multi-organ involvement have a poor prognosis, which can be improved by combination therapy with cyclophosphamide and highdose corticosteroid [6]. As cyclophosphamide induces severe toxicity, there have been many attempts to develop less toxic regimens

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Conclusion