title: Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis.
abstract: 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 At the first RTX administration, ongoing immunosuppressives were withdrawn.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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK federico.alberici@gmail.com.
authors.forename: Federico
authors.initials: F
authors.lastname: Alberici
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Rona M
authors.initials: RM
authors.lastname: Smith
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Jones
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Darren M
authors.initials: DM
authors.lastname: Roberts
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Willcocks
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Afzal
authors.initials: A
authors.lastname: Chaudhry
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Department of Medicine, University of Cambridge School of Clinical Medicine, Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, UK, Department of Clinical and Experimental Medicine, University of Parma, Italy and Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: David R W
authors.initials: DR
authors.lastname: Jayne
mesh_terms: D000328:Adult; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D000069283:Rituximab; D011239:Prednisolone
keywords: B cells; anti-neutrophil cytoplasm antibody; biologic therapies; granulomatosis with polyangiitis; maintenance treatment; microscopic polyangiitis; vasculitis