Journal
ANNALS OF THE RHEUMATIC DISEASES
Volume 74, Issue 9, Pages 1734-1738Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/annrheumdis-2014-206496
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Funding
- Roche
- GSK
- BMS
- Abbott
- Pfizer
- MSD
- Novartis
- UCB
- National Institutes of Health Research (NIHR) [RTF/01/097, DRF-2014-07-155] Funding Source: National Institutes of Health Research (NIHR)
- Cancer Research UK
- Versus Arthritis [18475] Funding Source: researchfish
- National Institute for Health Research [CS-2013-13-032, ACF-2012-02-004, DRF-2014-07-155, RTF/01/097] Funding Source: researchfish
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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.
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