Rituximab noninferior to conventional therapy in ANCA-associated vasculitis: RAVE Trial

Image: PD/Rituximab (Rituxan, MabThera)

1. At 18 months, patients with ANCA-associated vasculitis treated with one course of rituximab had similar outcomes in terms of inducing remission when compared to patients treated with conventional continuous immunosuppression therapy.

2. The overall rate of adverse events was similar between both groups; however, patients treated with rituximab had lower incidences of leucopenia and pneumonia. 

Evidence Rating Level: 1 (Excellent) 

Study Rundown:  Granulomatosis with polyangiitis (GPA, formerly Wegener’s) and microscopic polyangiitis (MPA) are systemic vasulidites that are caused by antineutrophil cytoplasmic antibodies (ANCA).  They both can cause renal and pulmonary damage, and are nearly indistinguishable clinically.  Traditionally, patients with these diseases are treated with toxic immunosuppression therapy involving cyclophosphamide and azathioprine.  Recently, the monoclonal anti-B-cell antibody rituximab has been shown to be successful as a treatment for ANCA-associated vasculidites, but its long term efficacy was not known.  This study suggests that patients with severe ANCA-associated vasculitis treated with rituximab had similar outcomes at 18 months when compared to patients treated with conventional therapy.  Even though the results suggest a significantly higher rate of remission among patients who received rituximab, the data did not meet criteria to show superiority, only noninferiority.  While the overall rate of adverse events was similar between the groups, patients treated with rituximab appeared to have lower rates of leucopenia and pneumonia.  The results are not generalizable to patients with vasculidites severe enough to cause advanced renal disease or require ventilatory support, as such patients were excluded from the study.

Click to read the study in NEJM

Relevant Reading: Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis

In-Depth [randomized double-blind non-inferiority study]: This study examined the outcomes of patients with severe ANCA-associated vasculidites treated with rituximab or conventional therapy for 18 months.  The authors enrolled a total of 197 patients with positive serum assays for either proteinase 3-ANCA or myeloperoxidase-ANCA with severe disease, which was defined as vital-organ involvement that posed an immediate threat to the function of the organ or the patient’s life.  They used the Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis to grade patients on their level of disease activity.  The authors randomized 99 patients to receive rituximab + placebo and 98 to receive conventional therapy consisting of cyclophosphamide and azathioprine.  Both treatment groups received an identical steroid taper that ceased after 5.5 months.  Follow up at 12 and 18 months compared the percentage of patients who had a BVAS/WG score of 0, had completed the steroid taper and had no relapse or treatment failure.

A total of 124 patients completed the 18 month follow up.  64% of patients who received rituximab had achieved remission at 6 months, and 39% maintained remission at 18 months; 53% of patients on conventional therapy achieved remission at 6 months of which 33% maintained remission at 18 months (P<0.001).  Additionally, patients receiving rituximab had fewer episodes of leucopenia and fewer episodes of pneumonia compared to those who received cyclophosphamide-azathioprine.

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