Induction Therapy for Pediatric ANCA Vasculitis
For pediatric patients with ANCA-associated vasculitis, the recommended induction therapy is a combination of glucocorticoids with either cyclophosphamide or rituximab, with rituximab increasingly preferred due to its favorable safety profile and efficacy. 1, 2
Disease Classification and Treatment Approach
- ANCA-associated vasculitis should be categorized according to severity to guide appropriate treatment decisions: localized, early systemic, generalized, severe, or refractory 1, 2
- Treatment intensity should be tailored based on disease severity, with more aggressive therapy for organ or life-threatening manifestations 1
- Pediatric ANCA vasculitis commonly presents with more severe ear-nose-throat involvement compared to adults 3
First-Line Induction Therapy Options
Cyclophosphamide-Based Regimen
- Cyclophosphamide can be administered as:
- Dose adjustments are necessary for reduced renal function (reduce by 0.5 mg/kg/day for oral or 2.5 mg/kg for IV if GFR <30 ml/min/1.73 m²) 1
- MESNA should be administered with cyclophosphamide to prevent hemorrhagic cystitis 1, 2
Rituximab-Based Regimen
- Rituximab dosing: 375 mg/m² weekly for 4 weeks 1, 4
- Can be combined with limited cyclophosphamide (15 mg/kg at weeks 0 and 2) for severe disease 1, 5
- Recent evidence shows increasing use of rituximab in pediatric ANCA vasculitis with favorable outcomes 3
Glucocorticoid Regimen
- Initial therapy typically includes:
- Recent evidence suggests reduced-dose glucocorticoid regimens (0.5 mg/kg/day) may be as effective as high-dose regimens (1 mg/kg/day) with fewer adverse effects 1, 6
- A structured tapering schedule should be followed as outlined in the PEXIVAS trial 1
Special Considerations
Severe Disease
- For patients with severe disease (creatinine >5.6 mg/dl or other vital organ failure):
- Consider plasma exchange for patients with serum creatinine >3.4 mg/dl (>300 mmol/l), requiring dialysis, rapidly increasing creatinine, or diffuse alveolar hemorrhage with hypoxemia 1
- More intensive immunosuppression with combination therapy (rituximab plus limited cyclophosphamide) may be beneficial 1, 5
Supportive Care
- All patients receiving cyclophosphamide should receive Pneumocystis jirovecii pneumonia prophylaxis with trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) 1, 2
- Regular monitoring of blood counts, renal function, and urinalysis is essential 2
Emerging Therapies
- Avacopan (C5a receptor antagonist) may be considered as an alternative to glucocorticoids in combination with rituximab or cyclophosphamide, particularly in patients at high risk for glucocorticoid toxicity 1
- Mycophenolate mofetil (2000 mg/day in divided doses) may be considered for non-severe disease, particularly in MPO-ANCA positive patients 1
Transition to Maintenance Therapy
- After achieving remission, transition to maintenance therapy with either:
- Maintenance therapy should typically be continued for 18 months to 4 years after induction of remission 1
Common Pitfalls and Caveats
- Wide variation in glucocorticoid dosing exists in pediatric ANCA vasculitis treatment, with higher doses not necessarily associated with improved outcomes but potentially more adverse effects 7
- Despite advances in treatment, kidney outcomes remain poor in pediatric ANCA vasculitis with a substantial proportion developing chronic kidney disease (54.8% at 1 year) 3
- P-ANCA positivity may be associated with higher relapse risk in pediatric patients 3
- Addition of pulse intravenous methylprednisolone to standard therapy may not confer additional clinical benefit and may be associated with more infections and higher incidence of diabetes 8