[Chiba Medical Society Award Review] Paradigm change in treatments for ANCA-associated vasculitis

[ABSTRACT] In the 2010s, the standard therapies for induction of remission in anti-neutrophil cytoplasm antibody (ANCA) -associated vasculitis were high-dose glucocorticoids combined with either cyclophosphamide or rituximab. These therapies resulted in high remission rates but were associated with a significant risk of infections. Consequently there was an unmet medical need to reduce the glucocorticoid dose and glucocorticoid-related side effects. Three pivotal trials, LoVAS, PEXIVAS, and ADVOCATE, were undertaken to address this need. The LoVAS trial, conducted in Japan, demonstrated that a reduced-dose glucocorticoid regimen was not inferior to the conventional high-dose glucocorticoid regimen, and resulted in a significant decrease in adverse events, especially serious infections, without compromising efficacy. The PEXIVAS trial in patients with severe glomerulonephritis also showed that a rapid tapering of glucocorticoid dose was as effective and safer than the conventional highdose glucocorticoid regimen. Lastly, the ADVOCATE trial evaluated avacopan, a C5a receptor inhibitor, and demonstrated its potential to reduce the glucocorticoid doses for induction of remission. In the avacopan group, the dose of glucocorticoid was limited to less than 20 mg/ day of prednisolone within four weeks, separate from methylprednisolone pulse therapy. In conclusion, these trials collectively signaled a paradigm shift in the treatment of ANCAassociated vasculitis and provided a clear message that reduced-dose glucocorticoid regimens were as effective as the conventional high-dose glucocorticoid regimens and were associated with a decrease in treatment-related adverse events and improved patient outcomes. Based on the results of these three clinical trials the updated guidelines in the 2020s now recommend these reduced-dose glucocorticoid regimens.