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

MYM Yusof, EM Vital, S Das, S Dass… - Annals of the …, 2015 - ard.bmj.com
MYM Yusof, EM Vital, S Das, S Dass, G Arumugakani, S Savic, AC Rawstron, P Emery
Annals of the rheumatic diseases, 2015ard.bmj.com
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 2× 1000
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 …
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 2×1000 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 naļve 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 naļve 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 naļve repopulation at 6 months, and 31% and 54% without naļve repopulation.
Conclusions
Responses to B cell depletion therapy are long-lasting and relapse post-treatment may be predicted by absence of naļve B cell repopulation at 6 months. Naļve B-lymphopenia may be a biomarker of disease activity in AAV.
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