Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis

OBJECTIVE: ANCA-associated vasculitis (AAV) is characterized by a chronic relapsing course. Rituximab (RTX) is an effective maintenance treatment; however, the long-term outcomes after its discontinuation are unclear. The aim of this study was to explore the long-term outcomes of AAV patients treated with repeat-dose RTX maintenance therapy. METHODS: AAV patients receiving a RTX treatment protocol consisting of an induction and maintenance phase were included. For initial remission induction, RTX was dosed at 1 g every 2 weeks or 375 mg/m(2) weekly for 4 consecutive weeks and for remission maintenance at 1 g every 6 months for 24 months. At the first RTX administration, ongoing immunosuppressives were withdrawn. RESULTS: Sixty-nine patients were identified, 67 of whom were failing other therapies. Nine relapsed during the RTX treatment protocol; however, all 69 were in remission at the end of the maintenance phase on a median prednisolone dose of 2.5 mg/day and 9% were receiving additional immunosuppression. During subsequent observation, 28 patients relapsed a median of 34.4 months after the last RTX infusion. Risk factors for relapse were PR3-associated disease (P = 0.039), B cell return within 12 months of the last RTX infusion (P = 0.0038) and switch from ANCA negativity to positivity (P = 0.0046). Two patients died and two developed severe hypogammaglobulinaemia. CONCLUSION: This study supports the efficacy and safety of a fixed-interval RTX maintenance regimen in relapsing/refractory AAV. Relapses after discontinuation of maintenance therapy did occur, but at a lower rate than after a single RTX induction course. PR3-associated disease, the switch from ANCA negative to positive and the return of B cells within 12 months of the last RTX administration were risk factors for further relapse.