Targeting the complement system in ANCA-associated vasculitis management.

ANCA-associated vasculitis (AAV) is a group of chronic multisystem inflammatory disorders affecting multiple organs throughout the body. Despite advances in AAV therapies, patients with AAV continue to experience higher rates of mortality than the general population. AAV outcomes can be improved by providing patients with rapid access to multidisciplinary medical teams and early treatment with glucocorticoid- (GC-) based therapy. However, GCs are associated with a high risk of toxicity. The phase 3 ADVOCATE trial demonstrates that blocking the alternative complement pathways using avacopan alongside immunosuppression enables patients with AAV to reduce their GC exposure without compromising efficacy or safety outcomes. ADVOCATE subgroup analyses show benefits for avacopan in patients with a wide range of AAV-related manifestations, disease stages and ages, with the greatest benefits in patients with kidney impairment, lung manifestations and AAV relapse.