Rituximab Dosing for Relapsed EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA)
For relapse of EGPA, administer rituximab 375 mg/m² IV weekly for 4 doses OR 1,000 mg IV on days 1 and 15, combined with glucocorticoids. 1
Induction Dosing for Relapse
The 2021 ACR/Vasculitis Foundation guideline provides two equivalent rituximab regimens for remission induction in EGPA relapse 1:
- 375 mg/m² IV weekly for 4 weeks (standard lymphoma dosing)
- 1,000 mg IV on days 1 and 15 (two-dose regimen)
Both regimens are explicitly listed for remission induction therapy in EGPA and should be combined with glucocorticoids (pulse IV methylprednisolone 500-1,000 mg/day for 3-5 days or high-dose oral prednisone 1 mg/kg/day) 1. The FDA label confirms these same dosing schedules for GPA/MPA, which applies to EGPA by extension 2.
Rationale for Rituximab in EGPA Relapse
Rituximab is preferred over cyclophosphamide for relapsing AAV, including EGPA. The 2024 KDIGO guideline specifically states that "rituximab is therefore preferred for relapsing AAV" with higher remission rates seen in relapsing patients, especially those with PR3-ANCA positivity 3. While EGPA has less robust trial data than GPA/MPA, the principle of preferring rituximab for relapse applies across all ANCA-associated vasculitides.
For severe EGPA relapse (life- or organ-threatening manifestations like alveolar hemorrhage, glomerulonephritis, cardiac involvement, or mononeuritis multiplex), rituximab or cyclophosphamide are conditionally recommended over mepolizumab, as mepolizumab's efficacy in severe disease has not been established 1.
Maintenance Dosing After Relapse
Following successful induction, transition to maintenance therapy 1, 3:
- 500 mg IV every 6 months (MAINRITSAN scheme), OR
- 1,000 mg IV every 4 months (RITAZAREM scheme - specifically studied in relapsing disease)
The RITAZAREM protocol (1,000 mg at complete remission, then at months 4,8,12, and 16) was specifically designed for relapsing AAV and showed >90% remission rates by 4 months 3. This may be particularly appropriate for EGPA patients with a history of relapse.
Special Considerations for EGPA
ANCA status matters: ANCA-positive EGPA patients show better response to rituximab than ANCA-negative patients 4. In the largest case series, ANCA positivity at baseline was associated with higher remission rates at 12 months 4. However, rituximab can still be effective in ANCA-negative EGPA with severe vasculitic manifestations 5.
Combination with mepolizumab: For refractory cases or those with prominent asthma/eosinophilic features, consider adding mepolizumab 300 mg SC every 4 weeks to rituximab, though this combination is based on case reports rather than trials 6, 7.
Glucocorticoid Co-Administration
Always administer methylprednisolone 100 mg IV (or equivalent) 30 minutes prior to each rituximab infusion to reduce infusion reactions 2. Continue oral glucocorticoids at 5-7.5 mg/day during maintenance for at least 2 years, then taper by 1 mg every 2 months 3.
Common Pitfalls
- Don't delay treatment for fertility concerns - while rituximab's long-term fertility effects are unknown, it's safer than cyclophosphamide in this regard 8
- Monitor for hypogammaglobulinemia - rituximab can cause declining immunoglobulin levels, particularly with repeated dosing 9
- Don't use mepolizumab alone for severe relapse - it's only proven for non-severe disease 1
- Ensure adequate B-cell depletion - peripheral CD19+ B cells should deplete to <10 cells/µL after the first two infusions 2