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.