Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Two Year Follow-Up Results from a Randomised Trial of Rituximab Versus Cyclophosphamide for Generalized' ANCA-Associated Vasculitis: RITUXVAS.
Jones1, Rachel B., Tervaert5, Jan Willem Cohen, Hauser4, Thomas, Luqmani7, Raashid, Morgan11, Matthew D., Peh8, Chen Au, Savage11, Caroline O.
Addenbrooke's Hospital, Cambridge, United Kingdom
University Hospital of Skane and Lund University
University of Birmingham, Birmingham, United Kingdom
Immunologie-Zentrum Zürich, Zurich, Switzerland
Maastricht University Medical Center, Maastricht, The Netherlands
Maastricht University Medical Center
Nuffield Orthopaedic Centre, Oxford, United Kingdom
Royal Adelaide Hospital, Adelaide, Australia
University Hospital of Skane and Lund University, Lund
Cyclophosphamide based induction regimens are standard therapy for ANCA-associated vasculitis with major organ involvement; however, associated mortality and adverse event rates are high and safer regimens are required. Rituximab based regimens are a potential alternative to cyclophosphamide induction.
We report the two year results of a randomised trial comparing a rituximab based induction regimen with a standard intravenous cyclophosphamide regimen for new ANCA-associated renal vasculitis. All patients had newly diagnosed ANCA-associated vasculitis with active renal disease and ANCA positivity. 44 patients were randomised; 33 to rituximab 4×375mg/m2 & 2×15mg/kg intravenous cyclophosphamide; and 11 to intravenous cyclophosphamide 610×15mg/kg. Both groups received the same intravenous and oral prednisolone regimen.
At entry: median age was 68 years, Wegener's granulomatosis 50%, microscopic polyangiitis 50%; CRP 28; BVAS 18; PR3-ANCA 57%, MPO-ANCA 43%, glomerular filtration rate 18ml/min, 20% required dialysis. At two years, the primary composite outcome of relapse, death or end stage renal failure occurred in 14/33 (42%) Rituximab versus 4/11 (36%) cyclophosphamide (p=1.00). Relapse occurred in 7/33 (21%) rituximab versus 2/11 (18%) cyclophosphamide (p=1.00), death in 6/33 (18%) rituximab versus 3/11 (27%) cyclophosphamide (p=0.67) and end stage renal failure in 2/33 (6%) rituximab versus 0/11 cyclophosphamide (p=0.57). Median estimated glomerular filtration rate was 20 & 44ml/min/m2 in rituximab patients at 0 and 24 months respectively compared to 12 & 31ml/min/m2 in cyclophosphamide patients. Serious adverse events occurred in 61% rituximab (50 events, 20/33 patients) versus 36% cyclophosphamide (15 events, 4/11 patients) (incidence rate ratio 1.16; 95% confidence interval 0.642.22) (p=0.64).
Rituximab based induction therapy is efficacious but is not superior to intravenous cyclophosphamide at two years in terms of combined relapse, mortality and end stage renal failure outcome. Further strategies to reduce mortality and serious adverse events and prevent relapse should be considered.
To cite this abstract, please use the following information:
Jones, Rachel B., Tervaert, Jan Willem Cohen, Hauser, Thomas, Luqmani, Raashid, Morgan, Matthew D., Peh, Chen Au, et al; Two Year Follow-Up Results from a Randomised Trial of Rituximab Versus Cyclophosphamide for Generalized' ANCA-Associated Vasculitis: RITUXVAS. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :676