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

Federico Alberici; Rona M Smith; Rachel B Jones; Darren M Roberts; Lisa C Willcocks; Afzal Chaudhry; Kenneth G C Smith; David R W Jayne

doi:10.1093/rheumatology/keu452

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

Rheumatology (Oxford). 2015 Jul;54(7):1153-60. doi: 10.1093/rheumatology/keu452. Epub 2014 Dec 3.

Authors

Federico Alberici¹, Rona M Smith², Rachel B Jones², Darren M Roberts², Lisa C Willcocks², Afzal Chaudhry², Kenneth G C Smith³, David R W Jayne²

Affiliations

¹ 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.
² 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.
³ 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.

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.

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.

Keywords: B cells; anti-neutrophil cytoplasm antibody; biologic therapies; granulomatosis with polyangiitis; maintenance treatment; microscopic polyangiitis; vasculitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / drug therapy*
Antibodies, Monoclonal, Murine-Derived / administration & dosage*
Antibodies, Monoclonal, Murine-Derived / adverse effects
Antibodies, Monoclonal, Murine-Derived / therapeutic use*
Antirheumatic Agents / administration & dosage*
Antirheumatic Agents / adverse effects
Antirheumatic Agents / therapeutic use*
Cohort Studies
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Therapy, Combination
Female
Follow-Up Studies
Humans
Immunosuppressive Agents / administration & dosage
Immunosuppressive Agents / therapeutic use
Incidence
Longitudinal Studies
Male
Middle Aged
Prednisolone / administration & dosage
Prednisolone / therapeutic use
Recurrence
Retrospective Studies
Rituximab
Time Factors
Treatment Outcome

Substances

Antibodies, Monoclonal, Murine-Derived
Antirheumatic Agents
Immunosuppressive Agents
Rituximab
Prednisolone

Grants and funding

100140/Wellcome Trust/United Kingdom