Complement Inhibition in ANCA-Associated Vasculitis

Vladimir Tesar, Zdenka Hruskova, Vladimir Tesar, Zdenka Hruskova

Abstract

Efficacy of immunosuppressive treatment of Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is complicated by its toxicity. With the replacement of cyclophosphamide with rituximab, serious adverse events seem to be associated especially with high-dose corticosteroids. Activation of alternative complement pathway plays an important role in the pathogenesis of AAV. Avacopan (C5a receptor inhibitor) was demonstrated to have at least similar efficacy and better safety (in terms of corticosteroid-related adverse events) compared with high-dose corticosteroids in the induction treatment of AAV. Other modes of the inhibition of alternative complement pathway are currently tested in AAV or could be considered on the basis of the experience in other glomerular diseases.

Keywords: ANCA; ANCA - associated vasculitis; C5a; avacopan; complement.

Conflict of interest statement

VT was principal investigator in both CLEAR and ADVOCATE trials with avacopan. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Tesar and Hruskova.

Figures

Figure 1
Figure 1
Complement inhibition currently tested in glomerular disease. Eculizumab and ravulizumab are antibodies against factor C5 used primarily in atypical hemolytic uremic syndrome. Avacopan is an oral inhibitor of C5a receptor. Vilobelimab is an antibody against factor C5a. Narsoplimab is antibody against MASP and is currently tested in IgA nephropathy. Iptacopan is an oral factor B inhibitor currently tested in IgA nephropathy, membranous nephropathy, and C3 glomerulopathy.

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