Fourteen patients (64%) with kidney involvement achieved remission, and in seven patients (50%), no flare was seen during the follow-up period. Three patients had renal flare and were successfully re-treated with RTX. Seventeen patients had disease symptoms from airways and eyes at RTX initiation, whereas only 29% displayed ≥50% treatment response. Limited clinical improvement was seen in patients with endobronchial lesions and trachea-subglottic granulomatous disease. RTX is a potent therapeutic

option for ANCA-associated vasculitis refractory to conventional treatment. Best response may be expected in patients with vasculitic manifestations. Granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis,

is a life-threatening systemic autoimmune vasculitis NVP-BGJ398 characterized by a necrotizing, granulomatous inflammation that predominantly involves upper airways, lungs and kidneys. The disease involves RG7420 datasheet small and medium-sized vessels and is frequently associated with antineutrophil cytoplasmic antibodies (ANCA) recognizing proteinase-3 (PR3). The presence of cytoplasmic ANCA is observed in the majority of patients with active disease, and ANCA titre correlates often with the severity of the disease and response to treatment [1]. In vitro, ANCA causes neutrophil activation, resulting in a respiratory burst and the release of inflammatory cytokines. In a mouse model, the transfer of ANCA specific for MPO causes crescentic glomerulonephritis and small-vessel vasculitis [2], suggesting that ANCA-producing B cells may be directly involved in the disease pathogenesis as precursors of plasma cells producing ANCA [1, 3, 4]. Untreated, the disease usually progresses from a limited necrotizing granulomatous process Rolziracetam to a generalized vasculitis and leads

to fatal outcome in >90% of patients in 2 years with mean survival time of 5 months [5]. The advent of cyclophosphamide (CYC) therapy together with corticosteroids for the induction of remission has reduced the mortality greatly and has become a conventional treatment option of GPA. Although this therapy remains the most effective initial treatment for the active disease, this regimen is associated with toxicity, increased rate of severe infections and dose-related increases in rates of haematological and solid organ malignancies [6]. For this reason, several other immunosuppressive agents, including methotrexate, azathioprine, mycophenolate mofetil, have been used to maintain remission. Unfortunately, in up to 10% of patients, disease is refractory to conventional therapy [7]. Rituximab (RTX) is a chimeric monoclonal antibody directed against the CD20 antigen found on the surface of B lymphocytes. It induces 98% depletion of peripheral blood B cells, but only 40–70% of lymph node B cells are depleted [3].