Background/Purpose: Most subjects with ANCA –associated vasculitis (AAV) respond to treatment for remission induction, but predictors for complete disease remission are lacking. We have previously demonstrated that selected markers of inflammation and platelet activation (C-reactive protein (CRP), CD40 ligand (CD40L) interleukins (IL) 6 and 8, monocyte chemoattractant protein 1 (MCP-1), P-selectin and vascular endothelial growth factor (VEGF) are associated with disease activity in AAV. The aim of this study was to explore if levels of marker predict future complete remission in AAV.

Methods: Subjects were participants in the Rituximab versus cyclophosphamide for AAV clinical trial (RAVE). Subjects with active disease were randomized to either rituximab or cyclophosphamide in addition to treatment with glucocorticoids. Data from the baseline, 2-month, 4-month, and 6-month study visits were used for this analysis. Disease activity was assessed with Birmingham Vasculitis Score for Wegener’s Granulomatosis (BVAS/WG). Complete remission was defined as BVAS=0 at the 6-month visit on no prednisone and without preceding severe flare or treatment failure since enrollment. CRP, CD40L, IL-6, IL-8, MCP-1, P-selectin, and VEGF were measured by ELISA. To explore if marker levels at baseline, 2 months and 4 months predicted complete remission at 6 months, logistic regression was used with complete remission as the outcome variable and marker-tertiles as independent variables. In additional analyses, the raw marker levels and log-transformed marker levels were used as independent variables in the models. The associations of the change in marker levels at the 2 4-month visits (compared to the baseline visit), with complete remission at the 6-month visit were tested with logistic regression. All analyses were adjusted for the BVAS/WG score at the baseline, 2-month, or 4-month visits, as appropriate.

Results: 197 subjects participated in the RAVE trial. The mean BVAS/WG score at baseline was 8.37 (sd 3.13). At the 6-month visit, 115 subjects achieved complete remission. Subjects with CRP levels in the third tertile at the 2-month and 4-month visits had lower odds of achieving complete remission at 6 months and subjects with IL-8 levels in the  third tertile at the baseline, 2-month, and 4-month visits had lower odds of achieving complete remission at the 6-month visit compared to subjects in the lowest tertile (Table). In analyses using the raw or log-transformed marker levels, no marker was significantly associated with future remission, nor were changes in marker levels from the baseline visit associated with future complete remission.

Conclusion: High CRP and IL-8 levels measured during treatment for remission induction of AAV are inversely associated with achieving future complete remission.  These markers may be of prognostic value AAV.