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Patients with ANCA-associated vasculitis treated with conventional regimens are at increased risk of death compared with an age- and sex-matched population.

on behalf of the European Vasculitis Study GroupObjective. To determine the association between characteristics at diagnosis and the time to first relapse in a large cohort of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods. We studied long-term followup data from 4 clinical trials that included newly diagnosed patients with a broad spectrum of AAV severity and manifestations. Patient and disease characteristics at baseline were used in competing risk regression models with relapse as the event of interest and death as the competing event.Results. We assessed 535 patients with 1,804 patient-years at risk of relapse. At diagnosis, the median age was 60. Conclusion. Relapse of disease is common for patients with AAV. A creatinine level >200 moles/liter at the time of diagnosis is strongly associated with a reduced risk of relapse and may help guide monitoring and treatment of patients with AAV.

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Histopathological features in renal biopsies of patients with antineutrophil cytoplasmic antibody-associated vasculitis have predictive value for renal outcome in patients who receive standard treatment with cyclophosphamide and corticosteroids; however, whether the same holds true for rituximab-treated patients is unknown. We describe associations between renal histopathology and outcomes among patients treated with a rituximab-based regimen in the Randomized Trial of Rituximab versus Cyclophosphamide in ANCAAssociated Vasculitis trial. Two pathologists, blinded to clinical data, reviewed biopsies from 30 patients according to a standardized protocol that included assessment of T cell, B cell, and plasma cell infiltration, as well as scoring for tubulitis, interstitial inflammation, and glomerulitis. We did not observe associations between immunohistology scores and age, sex, estimated GFR at entry, or requirement for dialysis. However, tubulointerstitial inflammation was more severe among patients who had a positive test for the myeloperoxidase antineutrophil cytoplasmic antibody. In a multiple linear regression model, both CD3 + T cell tubulitis and tubular atrophy independently associated with estimated GFR at 12 months. Tubular atrophy remained an independent predictor at 24 months (P,0.01). These results suggest that in addition to anti-B cell therapy, therapy directed at T cells may improve renal outcomes in antineutrophil cytoplasmic antibody-associated vasculitis. Established treatment regimens for systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and GN, consisting of cyclophosphamide and high-dose glucocorticoids, target both T and B cells. Standard treatment is associated with serious adverse events and the accumulation of therapy-related adverse events is an important cause of early mortality. 1,2 Therefore, ongoing studies involve the search for treatments that improve rates of sustained remission while minimizing adverse events. Several small studies of off-label treatment with rituximab, an anti-CD20 mAb, suggest that it induces remission in patients with systemic AAV refractory to standard therapy. 3-11 A multicenter study of 65 patients with refractory AAV demonstrated peripheral B cell depletion in all patients after a first course of rituximab, and complete remission was achieved in 75% (n=49) of patients. 12 Of the 49 patients who experienced initial complete