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

Abstract

Rituximab has enriched our armamentarium in the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Two randomised controlled trials have shown that rituximab is non-inferior compared with cyclophosphamide followed by azathioprine for the induction of remission. The newly diagnosed patients in the Rituximab in ANCA-Associated Vasculitis (RAVE) and Rituximab Versus Cyclophosphamide in ANCA-Associated Vasculitis (RITUXVAS) trials had a numerically higher response rate in the cyclophosphamide/azathioprine arm, and the number of such patients treated with rituximab numbered <90. We are arguing that in newly diagnosed patients, the evidence for rituximab requires further confirmation and the length of experience with a cyclophosphamide-based induction therapy supports it continuing as the preferred first choice for induction. Also, there is an absence of information regarding rituximab as 'sole' remission induction along with steroids in patients with advanced renal presentations or lung haemorrhage. Reported side effects were similar in both trials; however, the number of participants with at least one serious adverse event following rituximab induction treatment was numerically higher in the RAVE trial. In addition, hypogammaglobulinaemia with the need of substitution in some cases and late-onset neutropaenia are complications not seen with cyclophosphamide. Over the longer term it is unclear what relapse prevention strategy should be employed after rituximab, and there was a trend to a higher relapse risk after rituximab in the RITUXVAS trial at 2 years. Further health economic studies are required to understand all the costs associated with rituximab. In the context of concomitant underlying infectious complications, in terms of fertility concerns, especially in young patients, and when malignancy is underlying we would recommend the use of rituximab as first-line therapy.

Keywords: ANCA-associated vasculitis; RAVE; RITUXVAS; cyclophosphamide; rituximab.