What is the role of rituximab in the remission maintenance of granulomatosis with polyangiitis (GPA)?

Updated: Aug 31, 2021
  • Author: Christopher L Tracy, MD; Chief Editor: Herbert S Diamond, MD  more...
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A retrospective review evaluated the relapse rate and tolerance of rituximab maintenance therapy in 28 AAV patients (four with microscopic polyangiitis, 24 with GPA). The patients received a median of four rituximab infusions of differing dose and frequency over 38 months. Combined treatment included corticosteroids and other immunosuppressives (azathioprine, mycophenolate mofetil, methotrexate, leflunomide) at the time of the first rituximab maintenance infusion, although most had their immunosuppressive medication held for an average of 8 months after their first infusion. Results suggest that rituximab effectively maintained remission with a good safety profile, confirming previous reports. [71, 79]

Rituximab proved more effective than azathioprine in the prospective Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trial. MAINRITSAN included 115 patients with AAV (87 of them with GPA) who had achieved remission with conventional cyclophosphamide-based therapy. At month 28, major relapse had occurred in 29% of patients in the azathioprine group and in 5% of patients in the rituximab group (P=0.002). Severe adverse events occurred at similar frequencies in the two groups. [88]

In MAINRITSAN, rituximab was given at a fixed 500-mg intravenous dose on days 0 and 14 after randomization, and then at months 6, 12, and 18. Azathioprine was given at a dosage of 2 mg/kg/day for 12 months, and then 1.5 mg/kg/day for 6 months and 1 mg/kg/day for 4 months. In addition, prednisone was further tapered to a low dose (approximately 5 mg daily), which was maintained for at least 18 months after randomization. [88]

On continuation of MAINRITSAN, rituximab maintained its superiority over azathioprine. At month 60, the major relapse-free survival rates were 49.4% with azathioprine and 71.9% with rituximab (P=0.003); minor and major relapse-free survival rates were 37.2% and 57.9%, respectively, (P=0.012), and overall survival rates were 93.0% and 100%, respectively (P=0.045). Cumulative glucocorticoid use was comparable. [89]

MAINRITSAN2 found that patients receiving maintenance rituximab on an individually tailored regimen received fewer rituximab infusions, but had did not experience significantly higher rates of relapse, than those receiving fixed-dose therapy. Patients in the tailored-therapy arm received a 500-mg rituximab infusion at randomization, with rituximab reinfusion only when CD19+ B-lymphocytes or ANCA had reappeared or the ANCA titer rose markedly based on testing every 3 months until month 18. Patients in the fixed-dose arm received a 500-mg rituximab infusion on days 0 and 14, then 6, 12, and 18 months after the first infusion. [90]

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