In a manuscript published this week in Arthritis & Rheumatism, Immune Tolerance Network (ITN) investigators sought to better understand the distinction between patients who did and did not achieve the primary endpoint in the RAVE Study (Rituximab for the Treatment of ANCA-Associated Vasculitis and Microscopic Polyangiitis). The RAVE study established rituximab (Rituxan®; Genentech), a B-cell depletor, as a treatment alternative to cyclophosphamide (standard of care) for remission induction in patients with ANCA-Associated Vasculitis (AAV), a severe autoimmune disease marked by certain type of antibody (ANCA) that targets the blood vessels. Although outcomes for patients with AAV have improved over the past decades, about a quarter of patients fail standard induction regimens due to persistent or recurrent disease. The current study sought to better understand characteristics that predicted outcomes at 6 months.
The investigators found that RAVE patients with a specific kind of ANCA type, PR3-ANCA, were at increased risk for severe flares between months 1 and 6 compared to those with other ANCA types in both the rituximab and the cyclophosphamide arm. They also found that neither a rise in ANCA antibody levels nor detectable B-cell counts during the first 6 months were good predictors of disease flares suggesting other inflammatory pathways may be more critical at this juncture (however, after 6 months combined ANCA-negativity and B-cell depletion marked lower probability for disease flare). Future studies should continue to investigate mechanisms that contribute to disease flares to help clinicians better understand circumstances for potential treatment successes or failures, and risk for relapses.