Pro: Should all patients with anti-neutrophil cytoplasmic antibody-associated vasculitis be primarily treated with rituximab?

Randomized controlled trials have shown that rituximab is non-inferior to cyclophosphamide followed by azathioprine (CYC/AZA) for remission induction in severe granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The efficacy of rituximab is on par with CYC/AZA for 18 months, for patients with GPA and MPA alike, and for patients with any degree of renal impairment. The Rituximab in ANCA-associated Vasculitis (RAVE) trial also showed superiority of rituximab for patients presenting with a severe disease relapse. An exploratory analysis of the RAVE data further suggests that rituximab may be preferable for PR3-ANCA-positive patients as superiority was also achieved in that subset. When considering treatment options for patients with disease presentations for which only non-inferiority has been documented, safety concerns, compliance issues, the overall cost of each treatment approach to the patient, to society and to insurers, as well as individual patient preferences all should affect the decision-making process. The trials failed to uncover any difference in adverse events between rituximab and CYC/AZA. However, daily oral cyclophosphamide given for 3-6 months has measurable negative effects on fertility. Rituximab has certain compliance and convenience advantages. When assessing cost, the overall cost of a treatment, the societal context of the individual patient and not merely the sticker price of the drug should be considered. For all of these reasons, the author believes that CYC/AZA should be reserved for patients with newly diagnosed, MPO-ANCA-positive disease who raise no fertility, compliance or malignancy concerns.