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Rituximab in the treatment of anti-neutrophil cytoplasm antibody-associated vasculitis.

The introduction of cyclophosphamide and high-dose glucocorticoids for anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) has allowed a reduction in 1-year mortality from 80% to 10-20%. AAV is now a chronic disease, and greater emphasis has turned to improving treatment-related toxicity, reducing relapses and providing alternative treatments for refractory disease. Rituximab, an anti-CD20 B cell-depleting therapy, has been used for over a decade in patients with AAV. Rituximab offers a significant advance in the treatment of these diseases. It has an established role for remission induction and is now being investigated as a remission maintenance agent. For remission induction, randomised trials have reported similar remission rates with rituximab and cyclophosphamide, and rituximab is now an approved alternative to cyclophosphamide in severe AAV. In clinical practice, rituximab is increasingly used for refractory and relapsing disease. Further remission induction data with rituximab for life-threatening renal and pulmonary disease may be provided by the ongoing PEXIVAS trial (NCT00987389). With standard therapies, 50% of patients with newly diagnosed AAV relapse by 5 years. Relapses are higher still in patients with known relapsing disease. For remission maintenance, treatment trials are comparing repeat rituximab dosing to azathioprine. The MAINRITSAN trial (NCT00748644) included mainly newly diagnosed AAV patients following cyclophosphamide induction therapy. The RITAZAREM trial (NCT01697267) is randomising patients with relapsing disease after rituximab induction therapy. Preliminary results with rituximab maintenance therapy are encouraging, although the optimal dosing regimen and duration has yet to be defined. Other areas for further investigation include remission maintenance therapy requirement after rituximab induction in newly diagnosed AAV, and the role of rituximab in eosinophilic granulomatosis with polyangiitis where no randomised data exists.

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