Presenter of 1 Presentation
O016 - ANTI-COMPLEMENT THERAPY IN ANCA-ASSOCIATED VASCULITIS AND BEYOND (ID 175)
Abstract
Background and Aims
Historically complement system was not considered to play a role in ANCA associated-vasculitis (AAV), whereas recent experimental and clinical studies have suggested that the complement cascade, through the alternative pathway, is deeply involved in the pathogenesis of AAV. C5a receptor (Cd88) blockade in mice was shown to protect against MPO vasculitis and Avacopan (formerly CCX168), which is a selective inhibitor of C5a receptor, was shown to reduce the pro-inflammatory effects of C5a.
Methods
The critical trials validating the possible use of Avacopan in clinical practice will be reviewed. A Phase 1 clinical trial in healthy volunteers aimed at examining safety. The Phase 2 trial CLEAR assessed the possibility to reduce or replace glucocorticosteroid in the treatment of AAV. The Phase 3 ADVOCATE trial compared the ability of an Avacopan-based regimen combined with Cyclophosphamide (CYC) or Rituximab (RTX) vs a glucocorticoid-based scheme to induce and sustain remission in AAV patients in the long term.
Results
Safety has been assured over a large range of doses. Compared to glucocorticosteroid-based scheme, the Avacopan regimen combined with CYC or RTX was non-inferior at week 26 and superior at week 52 in sustaining remission
Conclusions
The results of these trials opened new therapeutic prospects for patients with AAV. The possible indications for Avacopan in specific subsets of patients with AAV, and the putative implications in the treatment of other immune-mediated kidney diseases (e.g., C3 GN, lupus nephritis, membranous nephropathy, IgA nephropathy, and others) will be extensively examined.