Summary

First ACR/Vasculitis Foundation guideline for management of ANCA-associated vasculitis (GPA, MPA, EGPA), providing 26 recommendations + 5 position statements for GPA/MPA and 15 recommendations + 5 position statements for EGPA. Key themes: rituximab preferred over cyclophosphamide for remission induction and maintenance in severe GPA/MPA, mepolizumab introduced for non-severe EGPA, reduced-dose glucocorticoid regimens favored, and routine plasma exchange not recommended. All recommendations are conditional due to limited high-quality evidence. Avacopan was not considered (post-search FDA approval).

Key Recommendations

For active severe GPA/MPA, use rituximab over cyclophosphamide for remission induction, combined with glucocorticoids.
Do not routinely add plasma exchange to remission induction for active glomerulonephritis or alveolar hemorrhage; reserve for high-risk-of-ESKD patients or anti-GBM overlap.
Use a reduced-dose glucocorticoid regimen rather than standard-dose for remission induction in severe GPA/MPA.
For active non-severe GPA, initiate methotrexate plus glucocorticoids (preferred over cyclophosphamide, rituximab, azathioprine, MMF, or TMP-SMX).
For remission maintenance in severe GPA/MPA after induction, use rituximab over methotrexate or azathioprine; use scheduled re-dosing rather than ANCA/CD19-guided dosing.
If maintaining on non-biologic, prefer methotrexate or azathioprine over MMF, leflunomide, or TMP-SMX.
Give Pneumocystis jirovecii prophylaxis to GPA/MPA/EGPA patients receiving cyclophosphamide or rituximab.
Do not dose immunosuppression based on ANCA titers alone; treat clinical/lab/imaging-defined disease activity.
For relapse on rituximab maintenance, switch to cyclophosphamide; for relapse off rituximab, use rituximab over cyclophosphamide.
In refractory severe GPA/MPA, switch between rituximab and cyclophosphamide rather than combining; add IVIG as adjunct.
For active severe EGPA, use cyclophosphamide or rituximab (not mepolizumab) for induction; cyclophosphamide preferred for cardiac involvement.
For active non-severe EGPA, use mepolizumab plus glucocorticoids over MTX/AZA/MMF; for relapsing non-severe EGPA, add mepolizumab.
Obtain echocardiogram at EGPA diagnosis; use Five Factor Score to guide therapy.
Supplement immunoglobulin for rituximab-maintained patients with IgG <3 g/L and recurrent severe infections.
Treat actively inflamed subglottic/endobronchial stenosis and mass lesions in GPA primarily with immunosuppression rather than surgery.

Thresholds & Doses

Pulse IV methylprednisolone (adults): 500–1000 mg IV daily × 3–5 days; (children): 30 mg/kg/day (max 1000 mg) × 3–5 days
High-dose oral prednisone (adults): 1 mg/kg/day up to 80 mg/day; (children): 1–2 mg/kg/day up to 60 mg/day
Oral cyclophosphamide induction: up to 2 mg/kg/day for 3–6 months
IV cyclophosphamide induction: 15 mg/kg q2 weeks × 3, then 15 mg/kg q3 weeks × ≥3 doses (adults)
Rituximab induction (adults): 375 mg/m² IV weekly × 4 OR 1000 mg IV days 1 and 15
Rituximab maintenance: 500 mg IV q6 months (FDA-approved), 1000 mg IV q4 months, or 1000 mg IV q6 months
Methotrexate: up to 25 mg/week PO or SC
Azathioprine: up to 2 mg/kg/day
Mycophenolate mofetil: up to 1500 mg PO BID
Mepolizumab: 300 mg SC every 4 weeks (adults, EGPA)
Omalizumab: 300–600 mg SC every 2–4 weeks
IVIG replacement (hypogammaglobulinemia): 400–800 mg/kg/month; treatment dose for refractory disease: 2 g/kg
Hypogammaglobulinemia threshold triggering Ig supplementation consideration: IgG <3 g/L with recurrent infections
PJP prophylaxis triggered by cyclophosphamide, rituximab (×≥6 months post-last dose), or prednisone >20 mg/day plus MTX/AZA/MMF
Five Factor Score (1996) components: proteinuria >1 g/day, serum creatinine >1.58 mg/dL, GI involvement, cardiomyopathy, CNS involvement

Citations

Table 1 — definitions of severe vs non-severe disease and drug dosing regimens
Table 2 — full list of 26 GPA/MPA recommendations and position statements with evidence levels
Table 3 — full list of 15 EGPA recommendations and position statements with evidence levels
Recommendation 1 (GPA/MPA) — rituximab over cyclophosphamide for severe induction
Recommendations 2–4 (GPA/MPA) — plasma exchange and reduced-dose glucocorticoid guidance
Recommendations 9–14 (GPA/MPA) — remission maintenance hierarchy (RTX > MTX/AZA > MMF/leflunomide/TMP-SMX)
Recommendations 1–4 (EGPA) — induction strategy including mepolizumab for non-severe disease
Recommendations 13–14 (EGPA) — echocardiogram at diagnosis and Five Factor Score use