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Abstract: TH-PO567

A Case of ANCA-Associated Vasculitis with IgG4-Related Disease Treated with the C5a Receptor Inhibitor Avacopan

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Kudo, Akiko, Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
  • Fukuda, Akihiro, Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
  • Okita, Jun, Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
  • Uchida, Hiroki, Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
  • Nakata, Takeshi, Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
  • Uesugi, Noriko, Department of pathology, Fukuoka University, Fukuoka, Japan
  • Shibata, Hirotaka, Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
Introduction

Complement is important in the immune system against infection but complement hyperactivation can cause complement-related disease, such as systemic lupus erythematosus. Recently, the C5a inhibitor avacopan was developed for treating antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). IgG4-related disease (IgG4-RD) is often associated with hypocomplementemia. C5a inhibitors may be effective in treating IgG4-RD, but this not been reported. We report the first case of AAV with IgG4-RD treated with avacopan.

Case Description

A 69-year-old man was admitted to our hospital because of fever, weight loss, anemia and urinalysis abnormalities. A blood test showed mild kidney dysfunction and elevated CRP, MPO-ANCA and serum IgG4 levels. An enhanced computed tomography (CT) scan showed bilateral renal swelling and multiple low-density lesions in the renal cortex. A renal biopsy showed pauci-immune type crescentic nephritis with necrotizing vasculitis. There was also prominent infiltration of IgG4-positive plasma cells with interstitial fibrosis called “storiform fibrosis,” which led to the diagnosis of coexistence of AAV and IgG4-RD. Remission induction therapy with glucocorticoids (GCs) and rituximab was followed by maintenance therapy with avacopan. One month later, the Birmingham vasculitis activity score (BVAS) improved from 15 to 0. Six months later, the renal low-density lesions on CT scan disappeared. GCs were tapered early with concomitant use of avacopan, and remission was maintained.

Discussion

Avacopan is a selective C5a receptor antagonist that blocks the inflammatory neutrophil response, including degranulation and release of reactive oxygen species. In the ADVOCATE study, avacopan was noninferior in the treatment response compared with GCs, and superior in reducing relapse and GC toxicity. GCs are the first-line treatment for IgG-RD, but the optimal treatment is unclear. Serum C5a levels in IgG4-RD were reported to be significantly higher than those in healthy donors and decreased at remission. These data suggest that avacopan may have been effective for not only AAV, but also for IgG4-RD, in our case.