Background: Avacopan has been approved for the treatment of ANCA-associated vasculitis (AAV) and the most recent, European guidelines avacopan recommend to use avacopan as steroid-sparing agent for the management of severe and active AAV patients, based on the findings of the landmark ADVOCATE study [1, 2]. However, all published randomized clinical trials have not treated AAV patients with avacopan beyond one year, resulting in a pivotal lack of evidence prompting guidelines to recommend no more than 12 months avacopan treatment [1, 2]. Nonetheless, it is self-evident that there is an urgent unmet need to address the gap of knowledge on prolonged avacopan treatment notably for AAV patients with refractory disease or frequently relapsing disease.

Objectives: Determine characteristics and clinical outcomes in patients who continued avacopan treatment longer than the recommended one-year duration.

Methods: The AVAC-EUR study is a multicenter, European retrospective, observational study to investigate avacopan use since its early access availability from 2020 onwards. In order to investigate prolonged avacopan treatment, we selected all patients with >1.5 years of follow-up since the start of avacopan (regardless of treatment duration). We compared patients treated with <1 year avacopan treatment versus prolonged avacopan treatment (defined as >1 year). We described patient characteristics, treatment characteristics and three important clinical outcomes (relapses, hospitalizations and infections).

Results: We identified 13 of the 32 patients in the AVAC-EUR database had a follow-up time of >1.5 years. Seven patients had prolonged avacopan treatment with a median [IQR] avacopan treatment of 3.1 [2.8-3.2] years and a total follow-up time of 3.1 [3.1-3.6] years. Six patients had <1 year avacopan treatment with a median avacopan treatment of 1.0 [0.5-1.0] years and a total follow-up time of 2.4 [1.6-4.4] years. Baseline characteristics are shown in Table 1. All patients achieved remission (BVAS =0) within 6 months. Three out of 7 patients with prolonged avacopan treatment stopped avacopan during follow-up, because of side effects (n=1), infection (n=1) or achieving sustained remission (n=1). In patients with <1 year avacopan treatment reasons to discontinue avacopan were side-effects (n=1), pregnancy wish (n=1), major flare (n=1), achieving sustained remission (n=2) and non-adherence (n=1). During the first year of follow-up, 6/7 patients with prolonged treatment received a steroid-taper and 3/7 (43%) patients received rituximab maintenance treatment. The median prednisone dosage was 15 [10-30] mg/day at baseline, 2.5 [0-5.6] mg/day after 6 months and 0 [0-3.8] mg/day after 12 months. Of the 6 patients with <1 year avacopan treatment, 5/6 patients received a steroid-taper and 4/6 (67%) received rituximab maintenance in the first year of follow-up. The median prednisone dosage was 23 [16-29] mg/day at baseline, 3.8 [0.6-6.9] mg/day after 6 months and 2.5 [0-5] mg/day after 12 months. In this first year, the relapse rate was 0.29 per patients year (PPY) (1 major and 1 minor relapse) for patient with prolonged treatment and 0.17 PPY (1 major relapse) for patients with <1 year avacopan treatment. Hospitalization rates and infections rates were lower in patients with prolonged treatment (0.14 an 0.43 PPY respectively) than in patients with <1 year treatment (0.83 and 0.67 PPY respectively). After the first year of follow-up, 3/7 patients with prolonged avacopan treatment continued steroids and 4/7 patients received RTX maintenance treatment. In patients were avacopan was discontinued 3/6 patients continued steroids, 3/6 received RTX maintenance treatment and 1/6 received azathioprine treatment. After the first year, the relapse rate was 0.13 PPY (2 minor relapses) in patients with prolonged avacopan treatment and 0.09 (1 major relapse) in patients with <1 year avacopan treatment. Hospitalization rates and infections rates remained lower in patients with prolonged treatment (0.20 and 0.33 respectively) than in patients with <1 year avacopan treatment (0.34 and 0.43 PPY respectively).

Conclusion: Our study is the first descriptive analysis of three years avacopan treatment in severe AAV patients in which we observed lower hospitalization and infection rates when compared to stopping avacopan treatment wihtin 1 year. These data warrant further confirmation in larger, observational studies including the currently recruiting AVAC-EUR study.

REFERENCES: [1] Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2023.

[2] Jayne DRW, Merkel PA, Schall TJ, et al. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. 2021;384(7):599-609.

Acknowledgements: NIL.

Disclosure of Interests: Jolijn R van Leeuwen: None declared, Luca Quartuccio for Abbvie and CSL Vifor, Iva Gunnarsson: None declared, Ben Sprangers for AstraZeneca, Vifor Pharma, Novartis, Takeda, EG, Boehringen, Y.K. Onno Teng The LUMC received consulting fees from Aurinia Pharmaceuticals, Novartis, GSK, KezarBio, Vifor Pharma, Otsuka Pharmaceuticals on consultancies delivered by YKOT, The LUMC has received an unrestricted research grant from CSL Vifor to conduct and coordinate the AVAC-EUR study by prof. Dr. Y.K.O. Teng and his team.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.