Repeat cycles of rituximab on clinical relapse in ANCA-associated vasculitis: identifying B cell biomarkers for relapse to guide retreatment decisions

Objective To assess clinical and B cell biomarkers to predict relapse after rituximab in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) using retreatment on clinical relapse strategy. Methods 35 patients with AAV received treatment with 2x1000 mg rituximab, repeated on clinical relapse (up to 5 cycles). Disease activity was assessed by Birmingham Vasculitis Activity Score (BVAS) and peripheral B cell subsets using highly sensitive flow cytometry (HSFC) as previously described; both performed at baseline and every 3 months. Results Response rates were high: > 83%, with median time-to-relapse of 82 weeks for cycle 1 (C1) and > 54 weeks for all cycles. Prior to rituximab, AAV was characterised by naive B-lymphopenia compared to healthy controls. This dysregulation was more marked in patients with raised C-reactive protein (CRP) (p< 0.05). In C1, no clinical feature predicted relapse. However, repopulation of naive B cell at 6 months was associated with a reduced risk of relapse (HR: 0.326, 95% 0.114 to 0.930, p= 0.036). Relapse rates at 12 and 18 months were 0% and 14% with naive repopulation at 6 months, and 31% and 54% without naive repopulation. Conclusions Responses to B cell depletion therapy are long-lasting and relapse post-treatment may be predicted by absence of naive B cell repopulation at 6 months. Naive B-lymphopenia may be a biomarker of disease activity in AAV.