Impact of rituximab trials on the treatment of ANCA-associated vasculitis

ANCA-associated vasculitis (AAV) is a subgrouping of autoimmune disorders characterized by a chronic relapsing course. Induction therapy is usually effective, but 70% of patients will relapse and 20% develop refractory disease. In the relapsing and refractory subgroups, treatment is complicated by the cumulative exposure to toxic drugs that contribute to poor long-term outcomes. The anti-CD20 monoclonal antibody rituximab (RTX) depletes B cells, and the success of this targeted therapy has contributed to the evidence supporting a central role for B cells in AAV pathogenesis. Initial proof of RTX effectiveness originated from small, prospective trials and retrospective surveys conducted in AAV patients with relapsing and refractory disease; high remission rates permitted the reduction of glucocorticoids (GCS) doses and withdrawal of immunosuppressives. There has been controversy over the effectiveness of RTX in patients with predominantly granulomatous manifestations, where response rates have varied between studies, in part due to different RTX dosing regimens. These studies were followed by comparison of RTX against cyclophosphamide (CYC) for remission induction of new or relapsing AAV in two randomized trials, which led to the licensing of RTX for this indication. Subsequent attention has been turned to the use of RTX as a relapse prevention agent, to the potential for GCS sparing and to RTX-associated toxicity. We will discuss the impact that the results of RTX clinical trials have had on the management of AAV patients.