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.