Rituximab, Cyclophosphamide, and Corticosteroids for ANCA Vasculitis: The Good, the Bad, and the Ugly

ANCA-associated vasculitis (AAV) frequently present with a chronic relapsing course. Relapse leads to an increased need for therapeutic agents and consequent toxicity.

When referring to the available options for the management of AAV, the efficacy of glucocorticoids (GCs) is unquestionable. However, similarly unquestionable are their side effects. It has been more than 40 years since the efficacy of cyclophosphamide (CYC) as an add-on therapy to GCs in the management of necrotizing vasculitis has been proven. At the same time, concerns about the devastating side effects related to a prolonged exposure to this agent were raised. Despite the well-known side effects, the management of AAV remained centred on CYC until the early 2000s, when the pilot data first supporting the anecdotal efficacy of rituximab (RTX) were reported. However, it was not until 2010 that the non-inferiority of RTX to CYC for remission-induction in AAVs was demonstrated in 2 randomized controlled trials. Key Messages: Treatment of AAV has improved over the last decade, and currently available strategies are able to induce remission in the majority of the cases. Herewith, we aim to critically review available evidence and to critically address the following question: How can we reduce the GCs use the management of patients with AAV? Novel strategies that avoid the toxicity associated with currently used agents should be the goal. Ideally, these approaches should be GC-free.