Complement inhibition in pediatric ANCA-associated vasculitis.

Abstract

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in childhood is a rare but severe condition associated with significant morbidity and treatment-related toxicity. Current therapies mainly rely on high-dose glucocorticoids and conventional immunosuppressants, which may cause substantial long-term adverse effects in pediatric patients. Advances in the understanding of AAV pathogenesis have identified the alternative complement pathway, particularly the C5a-C5a receptor axis, as a key driver of inflammation and vascular injury, leading to the development of complement-targeting therapies. While these agents have shown efficacy and steroid-sparing effects in adults, pediatric evidence remains limited to case reports and small case series. Available data suggest that complement inhibitors may represent a promising option for selected children with refractory disease, although concerns remain regarding dosing, long-term safety, and accessibility. This review summarizes current evidence, discusses unmet clinical needs, and highlights the need for collaborative pediatric studies and dedicated clinical trials.