Rituximab Dosing Regimen for Granulomatosis with Polyangiitis
For patients with granulomatosis with polyangiitis (GPA), rituximab should be administered at 375 mg/m² intravenously once weekly for 4 doses for remission induction, followed by maintenance therapy of 500 mg every 6 months. 1, 2
Remission Induction Therapy
- For active, severe GPA, rituximab is conditionally recommended over cyclophosphamide for remission induction due to comparable efficacy with potentially fewer long-term side effects 1
- The FDA-approved dosing regimen for induction therapy in GPA is 375 mg/m² IV once weekly for 4 weeks 2
- Alternatively, some clinicians use 1,000 mg on days 1 and 15 (two doses) for adult patients 1
- Rituximab should be administered with glucocorticoids, typically methylprednisolone 1,000 mg IV daily for 1-3 days followed by oral prednisone per clinical practice 2
- For pediatric patients, the recommended dose is 375 mg/m² IV weekly for 4 doses or 575 mg/m² for patients with body surface area ≤1.5m² (750 mg/m² for BSA >1.5m²) given as 2 doses on days 1 and 15 1
Remission Maintenance Therapy
- After achieving disease control with induction therapy, maintenance therapy with rituximab consists of 500 mg IV every 6 months 1, 3, 2
- Follow-up treatment should be initiated within 24 weeks after the last induction infusion, but no sooner than 16 weeks 2
- The MAINRITSAN protocol (referenced in guidelines) recommends 500 mg at complete remission and then at months 6,12, and 18 3
- Scheduled maintenance therapy with rituximab (500 mg every 6 months) has been shown to significantly reduce relapse rates compared to on-demand treatment 4
Special Considerations
- Premedication with antihistamines, acetaminophen, and glucocorticoids is recommended to reduce infusion-related reactions 2
- Prophylaxis against Pneumocystis jirovecii pneumonia with trimethoprim/sulfamethoxazole is recommended during rituximab therapy 1
- For patients with severe refractory disease, particularly those with diffuse alveolar hemorrhage or rapidly progressive glomerulonephritis, concurrent plasma exchange with rituximab may be considered 5
- Rituximab may be particularly preferred over cyclophosphamide in patients who wish to preserve fertility, as cyclophosphamide is associated with reduced ovarian reserve and male infertility 1
- Monitor for hypogammaglobulinemia during long-term rituximab therapy, as this has been reported in patients receiving prolonged treatment 6
Monitoring Response
- Disease activity should be monitored using validated tools such as the Birmingham Vasculitis Activity Score (BVAS) 7
- Complete remission is defined as absence of disease activity (BVAS of 0) 1
- ANCA-positive patients may have a better response to rituximab compared to ANCA-negative patients, particularly in eosinophilic granulomatosis with polyangiitis (EGPA) 8, 7
- Patients should be monitored for B-cell depletion (CD19+ B cells) during treatment 6
Differences in EGPA Treatment
- While rituximab is effective for GPA, the evidence for its use in EGPA is less robust 1
- For patients with active, severe EGPA, cyclophosphamide or rituximab is conditionally recommended over mepolizumab for remission induction 1
- In EGPA patients, rituximab has shown efficacy rates of 36-100%, with better responses typically seen in ANCA-positive patients 8
- For maintenance therapy in EGPA, rituximab (500 mg every 6 months) may be considered, particularly in those who achieved remission with rituximab induction 1
By following these evidence-based dosing recommendations, rituximab can effectively induce and maintain remission in patients with granulomatosis with polyangiitis, reducing disease activity and allowing for glucocorticoid dose reduction.