Background/Purpose: Avacopan is a novel C5a receptor inhibitor recently approved for treatment of ANCA-associated vasculitis as an alternative to glucocorticoids, It has demonstrated superior efficacy in achieving remission and improving renal outcomes. However, limited studies have compared the safety profiles, particularly the risk of severe infections, between avacopan and glucocorticoids in AAV patients. This meta-analysis aims to evaluate the combined risk of severe infections in patients treated with avacopan compared to those treated with glucocorticoids.

Methods: A comprehensive literature search was performed on Pubmed, Cochrane and Embase databases for randomized controlled trials (RTCs) comparing risk of infection in patients with ANCA-related vasculitis treated with Avacopan versus Glucocorticoids. Severe infection were defined as pneumonia, UTI, neutropenic sepsis, sepsis, fungal infection, reactivation of HSV, meningitis or others as specified by each study. Statistical analysis was performed using Review Manager 5.17. Heterogeneity was assessed by I2 statistics.

Results: A total of 681 patients from 5 RCTs were included, with 351 (51.5%) receiving avacopan. The mean age was 60.5 years (±14.5), and 46% were female. The follow-up duration ranged from 12 to 52 weeks. Pneumonia was the most commonly reported severe infection. Eight deaths due to severe infections were reported across the studies. The pooled relative risk (RR) for severe infections was 0.84 (RR 0.84; 95% CI: 0.62–1.15; p=0.9; I²=0%), indicating no statistically significant difference between the avacopan and glucocorticoid groups (Forest Plot 1). Similarly, the RR for death due to infection was 0.37 (RR 0.37; 95% CI: 0.09–1.61; p=0.64; I²=0%), showing no significant difference between the two treatment groups (Forest Plot 2).

Conclusion: In conclusion, treatment with Avacopan does not increase the risk of severe infection compared to glucocorticoid treatment in patients with ANCA-associated vasculitis. These results support current literature suggesting better overall outcomes of patients with ANCA-vasculitis treated Avacopan without an increased risk of infection.

Forest Plot 1

Forest Plot 2

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/avacopan-is-not-associated-with-an-increased-risk-of-infection-compared-to-glucocorticoids-in-patients-with-anca-associated-vasculitis/