# Evolving Therapeutic Strategies in ANCA-Associated Vasculitis: Current Standards and Emerging Targets for GPA and MPA

## TL;DR

This paper reviews current and emerging treatments for GPA and MPA, focusing on reducing steroid use and improving long-term outcomes through precision immunotherapy.

## Contribution

The paper highlights novel therapeutic strategies targeting specific immune pathways in ANCA-associated vasculitis.

## Key findings

- Rituximab-based maintenance therapy outperforms conventional oral agents in GPA and MPA.
- New therapies target B cells, plasma cells, complement components, and cytokine networks.
- Precision immunotherapy aims to reduce glucocorticoid exposure and long-term toxicity.

## Abstract

Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are severe autoimmune disorders characterized by necrotizing small-vessel inflammation, and are classified among anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). Standard induction therapy combines glucocorticoids (GCs) with rituximab (RTX) or cyclophosphamide (CYC), with growing emphasis on GC minimization and selective use of avacopan in patients at high risk of GC toxicity. For maintenance therapy, fixed-interval RTX generally outperforms conventional oral agents and biomarker-guided re-dosing in unselected populations, yet treatment should be individualized. Persistent challenges include treatment-related toxicity, refractory manifestations, and defining safe discontinuation strategies. Expanding knowledge of AAV immunopathogenesis has driven the development of novel, mechanism-based therapies. These include agents targeting B cells and plasma cells (anti-CD38, anti-CD19, proteasome inhibition, CAR-T cells), complement components, and T-cell co-stimulation or cytokine networks (abatacept, IL-6 and JAK-inhibitors). Collectively, these advances are shifting AAV care from broad immunosuppression toward precision immunotherapy aimed at durable remission with reduced GC exposure and minimized long-term toxicity.