298. Effect of Treatment with Avacopan on Patients with ANCA-Associated Vasculitis with Non-Major Manifestations of Disease
Creators: name: Merkel1, Peter
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> Patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are affected by a broad range of disease manifestations that range from life- or organ-threatening (severe) to less severe. Although considered less severe (moderate), many such manifestations of AAV result in tissue damage and chronic morbidity. It is often less severe issues, such as rhinosinusitis or arthralgias, that are associated with both relapse in AAV and chronic manifestations. <strong>Methods: </strong>ADVOCATE was a Phase 3, randomized, double-blind, controlled study. Patients were included if they had at least one major or three non-major BVAS items, or proteinuria and hematuria. They were randomized to receive a prednisone taper or avacopan with matching placebos on a background of either cyclophosphamide or rituximab. Primary efficacy endpoints were the proportion of patients achieving disease remission [BVAS of 0 and no glucocorticoids (GCs)] at Week 26 and sustained remission at Week 52. This post-hoc analysis examined the outcomes of patients with no major manifestation of AAV at the time of enrollment. <strong>Results</strong>: The ADVOCATE trial demonstrated the efficacy of avacopan, an oral selective C5a receptor antagonist, in the treatment of patients with AAV. Remission at Week 26 was achieved in 72% of patients in the avacopan group vs. 70% in the prednisone group, and sustained remission at Week 52 in 66% in the avacopan group and 55% in the prednisone group. The majority (~80%) of patients in this trial had active disease manifestations involving at least one major item on the Birmingham Vasculitis Activity Score (BVAS), including proteinuria and hematuria, at the time of enrollment. Sixty-three of 330 (19%) patients in ADVOCATE had only non-major BVAS items at the time of enrollment: avacopan group, n=32; prednisone group, n=31. Demographics and baseline characteristics are shown in Table 1. Compared to the overall study population, patients with non-major manifestations of disease were 55 years old (vs. 61 in the study population overall); 46% were male (vs. 56% overall); 54% had relapsed AAV (vs. 31% overall); 76% had PR3 AAV (vs. 43% overall); 86% had GPA (vs. 55% overall); 84% received rituximab (vs. 65% overall). Ear, nose, and throat was the most common organ system involved (86%) vs. Renal, 81% overall. The response to treatment among the 63 patients with only non-major manifestations of disease were as follows: in the avacopan group, 24 of 32 (75%) patients achieved remission at Week 26 compared to 17 of 31 (55%) patients in the prednisone group; 22 of 32 (69%) patients in the avacopan group achieved sustained remission at Week 52 compared to 13 of 31 (42%) patients in the prednisone group. Serious adverse events occurred in 7 (22%) of patients in the avacopan group vs. 12 (39%) in the prednisone group, and 4 (13%) in the avacopan group discontinued study medication due to adverse events vs. 7 (23%) in the prednisone group. <strong>Conclusions:</strong> In the ADVOCATE trial, a post-hoc, subset analysis, among patients with non-major manifestations of disease at enrollment suggests efficacy and safety with avacopan appears to be consistent with the overall findings of the study. <strong>Disclosures:</strong> Peter A. Merkel reports receiving consulting and research support from AbbVie, AstraZeneca, Boeringher-Ingelheim, Bristol-Myers Squibb, ChemoCentryx, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Takeda; consulting fees from CSL Behring, Dynacure, EMDSerono, Jannsen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, Pfizer, Sparrow, Talaris; royalties from UpToDate. David R.W. Jayne reports receiving consulting fees from AstraZeneca, ChemoCentryx, and Genentech and grant support, paid to the University of Cambridge, and consulting fees from GlaxoSmith-Kline. Pirow Bekker reports receiving consulting fees from and owning stock and stock options in ChemoCentryx. Huibin Yue reports employment and owning stock and stock options in ChemoCentryx