Rituximab in relapsing or refractory ANCA-associated vasculitis: a case series of 16 patients

Objectives: Cyclophosphamide (CYC) and corticosteroids are generally considered standard induction therapy for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, a subset of patients are refractory or intolerant to this treatment. Rituximab, a chimeric anti-CD20 antibody, has emerged as a second-line therapy, although controlled studies are scarce in patients with relapsing or refractory disease. Methods: We report 16 patients with AAV who received rituximab for refractory or relapsing vasculitis having previously received CYC. The treatment protocols were 375 mg/ m(2) x IV in five patients, 1000mg x II in six patients, and 500 mg x II in five patients, all in combination with corticosteroids. A majority of patients used other concurrent immunosuppression, most commonly mycophenolate mofetil. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS 2003) at baseline and during follow-up together with C-reactive protein (CRP) and ANCA. Complete remission was defined as a BVAS score of 0 and partial remission as a reduction in BVAS of at least 50%. Results: Twelve patients achieved complete remission, three patients partial remission, and one patient died during follow-up (median of 20 months, range 3-48 months). Six patients relapsed and received rituximab again. Four of these were positive for capture proteinase 3 (PR-3) ANCA but negative with conventional PR-3 ANCA upon retreatment. Seven patients had an adverse event, including two hepatitis B reactivations and one fatal sepsis. Conclusion: Treatment with rituximab in AAV was associated with prolonged remission in a subset of patients otherwise difficult to manage.