Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial.
OBJECTIVE
The RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 12 months; however, immunosuppression maintenance requirements and longer-term outcomes after rituximab in ANCA-associated renal vasculitis are unknown.


METHODS
Forty-four patients with newly diagnosed ANCA-associated vasculitis and renal involvement were randomised, 3:1, to glucocorticoids plus either rituximab (375 mg/m(2)/week×4) with two intravenous cyclophosphamide pulses (n=33, rituximab group), or intravenous cyclophosphamide for 3-6 months followed by azathioprine (n=11, control group).


RESULTS
The primary end point at 24 months was a composite of death, end-stage renal disease and relapse, which occurred in 14/33 in the rituximab group (42%) and 4/11 in the control group (36%) (p=1.00). After remission induction treatment all patients in the rituximab group achieved complete B cell depletion and during subsequent follow-up, 23/33 (70%) had B cell return. Relapses occurred in seven in the rituximab group (21%) and two in the control group (18%) (p=1.00). All relapses in the rituximab group occurred after B cell return.


CONCLUSIONS
At 24 months, rates of the composite outcome of death, end-stage renal disease and relapse did not differ between groups. In the rituximab group, B cell return was associated with relapse.


BACKGROUND
ISRCTN28528813.
Renal Unit, Addenbrooke's Hospital, Cambridge, UK.
Rachel B
http://orcid.org/0000-0003-4790-283X
RB
Jones
Renal Unit, Addenbrooke's Hospital, Cambridge, UK.
Shunsuke
S
Furuta
Clinical and Experimental Immunology, Maastricht University, Maastricht, The Netherlands.
Jan Willem Cohen
JW
Tervaert
IZZ Immunologie-Zentrum Zürich, Zürich, Switzerland.
Thomas
T
Hauser
Department of Rheumatology, Nuffield Orthopaedic Centre, Oxford, UK.
Raashid
R
Luqmani
Department of Renal Immunobiology, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Matthew D
MD
Morgan
Royal Adelaide Hospital and University of Adelaide, Adelaide, Australia.
Chen Au
CA
Peh
Department of Renal Immunobiology, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Caroline O
CO
Savage
Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Marten
M
Segelmark
The First Faculty of Medicine, Charles University, Prague, Czech Republic.
Vladimir
V
Tesar
Clinical and Experimental Immunology, Maastricht University, Maastricht, The Netherlands.
Pieter
P
van Paassen
Departments of Medicine (Nephrology) and Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada.
Michael
M
Walsh
Department of Nephrology and Transplantation in Malmo, University Hospital of Skane and Lund University, Malmo, Sweden.
Kerstin
K
Westman
Renal Unit, Addenbrooke's Hospital, Cambridge, UK.
David Rw
DR
Jayne
D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000166:cytology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D014890:Granulomatosis with Polyangiitis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000209:etiology; D018655:Lymphocyte Count; D008297:Male; D055953:Microscopic Polyangiitis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D000069283:Rituximab
D058846:Antibodies, Monoclonal, Murine-Derived; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D001379:Azathioprine
B cells; Cyclophosphamide; Granulomatosis with polyangiitis; Systemic vasculitis; Treatment