ANCA-associated vasculitis (AAV) — granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (EGPA) — has undergone a therapeutic revolution built on one central goal: maintaining efficacy while stripping away the toxicity of long-term glucocorticoids.
Avacopan: replacing steroids
Avacopan, an oral C5a receptor antagonist, was designed to substitute for much of the glucocorticoid burden in AAV. In the pivotal ADVOCATE trial it was non-inferior to a prednisone taper for inducing remission and superior for sustaining it at 52 weeks (72.3% vs 70.1%), with fewer glucocorticoid-related toxicities and a slightly lower rate of serious adverse events. It is now approved as an adjunct in AAV, though guidelines caution against its use in the most severe end-organ presentations (such as advanced renal failure or alveolar hemorrhage needing ventilation).
Rituximab and reduced-steroid regimens
Rituximab is established for both remission induction (non-inferior to cyclophosphamide in RAVE) and maintenance (superior to azathioprine for relapse prevention in RITAZAREM). The PEXIVAS trial reshaped supportive care in two ways: a reduced-dose glucocorticoid regimen was non-inferior to standard dosing for death or end-stage kidney disease while causing fewer serious infections, and plasma exchange did not improve those hard outcomes — findings that have driven steroid minimization across the field.
EGPA: two IL-5-pathway biologics
For EGPA specifically, IL-5-directed therapy has been transformative. Mepolizumab (IL-5 inhibitor) roughly tripled remission versus placebo in the MIRRA trial (about 52% vs 19%) while reducing glucocorticoid dose and flares. The key update is that benralizumab (an IL-5 receptor antibody) then proved non-inferior to mepolizumab in the head-to-head MANDARA trial, with more patients able to stop oral glucocorticoids, and was approved for EGPA in 2024 — giving clinicians two validated IL-5-pathway options.
| Therapy | Indication | Key result | Notes |
|---|---|---|---|
| Avacopan | AAV induction/maintenance | Superior sustained remission vs prednisone; steroid-sparing | Avoid in severe end-organ disease |
| Rituximab | AAV induction/maintenance | Non-inferior to cyclophosphamide; superior to azathioprine | Infection, hypogammaglobulinemia |
| Reduced-dose steroids (PEXIVAS) | Severe AAV | Non-inferior; fewer infections | Plasma exchange no benefit on death/ESKD |
| Mepolizumab | EGPA | Remission ~52% vs 19% | IL-5 inhibitor |
| Benralizumab | EGPA | Non-inferior to mepolizumab; more steroid discontinuation | IL-5 receptor antibody; approved 2024 |
Further reading: ADVOCATE avacopan (Jayne et al., NEJM 2021); RAVE, RITAZAREM, and PEXIVAS; MIRRA mepolizumab; MANDARA benralizumab (Wechsler et al., NEJM 2024); KDIGO 2024 AAV guideline.