In their recent report, Walsh et al (1) analyzed long-term followup data from 535 patients with newly diagnosed antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis who were included in 4 studies conducted by the European Vasculitis Study Group. Using sophisticated statistical models, they identified anti–proteinase 3 (anti-PR3) positivity and cardiovascular involvement at the time of diagnosis as risk factors for relapse during followup, whereas they found that advanced renal insufficiency (creatinine level >200 μmoles/liter) was associated with a lower risk of relapse. The data support, in part, the current knowledge that in patients with ANCA-associated vasculitis the presence of PR3 ANCA, the diagnosis of granulomatosis with polyangiitis (Wegener's), and the involvement of lung and/or upper airways disease are associated with a higher rate of relapse (2–4).
In general, a relapse is associated with patient morbidity and the need for intensified immunosuppressive therapy. However, not only the organ system involved, but also the severity of the relapse, is of great importance since both the type of treatment, as well as long-term risks of chronic organ damage and mortality, strongly depend on the severity of a relapse. It would therefore be helpful to analyze the data not only with regard to the presence of a relapse, but also according to the organ system involved and the severity of the relapse.
The association of cardiovascular involvement at the time of diagnosis with a higher risk of relapse has been described in 2 other reports to date (5, 6). It seems unlikely that the relapses occurred within the cardiovascular system considering the low frequency of cardiovascular involvement in ANCA-associated vasculitis. Nevertheless, it is difficult to explain why cardiovascular involvement should trigger a relapse in any other organ system. One may presume that the granulomatous aspect of cardiovascular involvement could be a link to a relapse of a granuloma, e.g., within the respiratory tract. A more detailed analysis of the organ systems in which the relapses occurred could shed light on this question.
Furthermore, Walsh and colleagues reported an increased risk of relapse with a higher number of risk factors (i.e., anti-PR3 positivity, cardiovascular involvement, or creatinine level ≤100 μmoles/liter). However, the curves of the 1–Kaplan-Meier estimates of relapse classified by the numbers of risk factors present at diagnosis seem to separate within the first 24 months and show a parallel course beginning ∼2 years after initial diagnosis. This would suggest that the risk of relapse within 2 years of diagnosis truly is associated with these 3 risk factors, but that thereafter different risk factors may be responsible for the occurrence of relapses. It will be of interest to investigate whether newer treatment strategies, including anti-CD20 antibodies, influence the risk of relapse and the kinds of risk factors in patients with ANCA-associated vasculitides.