POS0305 THE EFFICACY AND SAFETY OF AVACOPAN IN REMISSION INDUCTION THERAPY FOR MPA/GPA AND THE EFFECTS OF AVACOPAN ON SERUM C5a AND S100A9 LEVELS: A SINGLE-CENTER STUDY IN JAPAN
Authors: Y. Ushio, R. Wakiya, S. Nakashima, T. Miyagi, K. Sugihara, M. Mizusaki, R. Kagawa, H. Yamaguchi, H. Shimada, H. Dobashi
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> C5a production through activation of the complement pathway is a component of the pathogenesis of ANCA-associated vasculitis (AAV). In the ADVOCATE trial [1], avacopan, an oral C5a receptor inhibitor, was demonstrated to be an alternative to glucocorticoids (GC) in the treatment of microscopic polyangiitis (MPA)/granulomatosis with polyangiitis (GPA) and was approved in several countries including Japan. However, there are still few reports as for the efficacy and safety of avacopan in real clinical practice. Additionally, the impact of avacopan treatment on AAV biomarkers is also unclear. <h3>Objectives:</h3> We aimed to clarify the efficacy and safety of avacopan in remission induction therapy for MPA/GPA in real clinical practice, as well as changes in serum C5a and S100 A9 levels, which is biomarkers of vasculitis before and after treatment with avacopan. <h3>Methods:</h3> Patients with MPA/GPA who received remission induction therapy with GC plus rituximab or cyclophosphamide at our institution from January 2017 to June 2023 were included in this retrospective study. To evaluate the efficacy and safety of avacopan, patients were divided into two groups: one group received avacopan in combination with remission induction therapy (avacopan group) and the other group did not (non-avacopan group). The achievement rate of BVAS=0, daily GC dose (prednisolone-equivalent), and the incidence of adverse events (AEs) until 6 months after treatment were investigated and compared between the two groups using the Wilcoxon rank-sum test and Fisher's exact test. Serum C5a and S100A9 were measured in the avacopan group before and 3 months after treatment. The association of serum C5a or S100A9 with disease activity was analyzed. We also analyzed the effect of treatment on serum C5a or S100A9 using Wilcoxon's signed-rank test. <h3>Results:</h3> A total of 73 patients with MPA/GPA were included, 15 in the avacopan group and 58 in the non-avacopan group. There were no differences between the two groups in age, ANCA status, proportion of MPA/GPA, or type of remission induction therapy, except for gender proportion (Table 1). The achievement rate of BVAS=0 at 1, 3, and 6 months was not significantly different between the avacopan and non-avacopan groups (60.0% vs. 50.0%, 93.3% vs. 80%, 100% vs. 95.7%, respectively) (Figure 1). On the other hand, the mean daily GC dose at 1, 3, and 6 months was significantly lower in the avacopan group than in the non-avacopan group (14.5 ± 9.2 mg/day vs. 24.8 ± 9.4 mg/day, 6.1 ± 4.4 mg/day vs. 11.9 ± 4.0 mg/day, 3.0 ± 2.4 mg/day vs. 7.8 ± 2.8 mg/day, respectively) (Figure 1). The incidence of GC-related AEs (defined as hypertension, diabetes, osteoporosis, cataract and glaucoma, and severe infection) within 6 months was significantly lower in the avacopan group than in the non-avacopan group (6.7% vs. 50.0%, p&lt;0.01). Serum C5a and S100A9 were measured in 11 patients in the avacopan group. A significant positive correlation was observed between serum C5a levels and BVAS before treatment (ρ=0. 8111, p&lt;0.01). The median value of serum C5a increased from 75.3 ng/mL to 89.7 ng/mL while the median value of serum S100A9 decreased from 50.8 ng/mL to 30.8 ng/mL. In patients with higher serum C5a levels at the start of treatment, serum S100A9 tended to decrease after treatment with avacopan (Figure 1). <h3>Conclusion:</h3> In real clinical practice, avacopan was confirmed to be useful in achieving high remission rates and reducing GC doses and GC-related AEs. In addition, serum S100A9 may be a biomarker reflecting the therapeutic effect of avacopan. <h3>REFERENCES:</h3> [1] Jayne DRW, et al. N Engl J Med. 2021;384:599-609. <b>Table 1.</b> Clinical characteristics of the patients. RTX: rituximab; CY: cyclophosphamide; IQR: interquartile range. For statistical analyses * p&lt;0.05. p value: Wilcoxon rank sum test, Fischer's exact test <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>