Rituximab Treatment for Vasculitis

Abstract

The emergence of rituximab during the past decade as a new therapy for ANCA-associated vasculitis (AAV) has been the most important innovation in this disease area since cyclophosphamide 40 years ago. The article by Niles et al. (1) in this issue of CJASN adds to the evidence of its efficacy. For nephrologists, vasculitis usually means a necrotizing, crescentic glomerulonephritis associated with ANCA (2). Less frequent vasculitic renal disease includes immune complex glomerulonephritides in association with Henoch-Schonlein purpura or cryoglobulinemia or intra- and extra-renovascular disease associated with polyarteritis nodosa or Takayasu arteritis. ANCA-associated renal vasculitis has an annual incidence of 10 to 15 per million population and occurs in the context of a systemic vasculitis, such as Wegener granulomatosis or microscopic polyangiitis, or as an isolated entity (renal limited vasculitis) (3). Confusingly, approximately 5% of pauci-immune, crescentic glomerulonephritis is ANCA negative at diagnosis. The typical presentation of renal vasculitis is that of a rapidly progressive glomerulonephritis. With widespread ANCA testing and increased awareness, this condition is increasingly being diagnosed at an earlier stage before advanced renal failure is present (4). The outcomes of AAV are frequently poor: The mortality is 25% at 5 years, and 20% of survivors develop ESRD (5). Less severe chronic kidney disease persists in the majority and contributes to markedly increased rates of cardiovascular disease. GFR at diagnosis and myeloperoxidase (MPO)-ANCA positivity are predictive of both mortality and adverse renal outcome. Older patients are more likely to be MPO-ANCA positive, present with more advanced renal disease, are less tolerant of current therapies, and represent the most acute unmet need for newer therapies. The current standard of care has evolved to comprise the combination of high-dosage glucocorticoids with cyclophosphamide. This leads to control of disease in most patients, but treatment-related toxicity, especially infection, is the major cause …