Therapeutics controversies in antineutrophilic cytoplasmic antibody-associated vasculitis

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by inflammation of small- to medium-sized blood vessels with ANCAs. Induction therapy has historically involved cyclophosphamide (CYC) and glucocorticoids (GCS), with rituximab (RTX) emerging as a preferred alternative. Studies addressed the efficacy of RTX in severe kidney diseases, showing results comparable to CYC. In severe diseases that are unsuitable for high-dose CYC, combined RTX and low-dose CYC demonstrate promising results. There is a recent trend to administer low-dose GCS to reduce infections and other complications. Recent trials have questioned the broader role of plasma exchange (PLEX), influencing guidelines' updates. Current indications for PLEX include severe kidney dysfunction, positive glomerular basement membrane antibody, and diffuse alveolar hemorrhage that requires oxygen support at presentation. Maintenance therapy options include azathioprine, RTX, and methotrexate. RTX's efficacy as a maintenance agent was demonstrated in trials. However, controversies in dosing frequency persist. The optimal duration of maintenance therapy remains debated, with guidelines suggesting 18-48 months. More recent studies proposed longer durations to reduce the risk of relapse, thus challenging existing guidelines. Complement involvement in AAV has been increasingly recognized. Studies show that complement 3 depositions in the glomeruli correlate with severe disease and complement inhibitors such as avacopan demonstrated efficacy in the management of AAV. Other complement inhibitors, such as eculizumab and vilobelimab, are being explored. In conclusion, AAV management has made significant advances, but controversies persist. Future research should refine therapeutic regimens and explore novel targeted treatments for personalized medicine in AAV.