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Repeat cycles of rituximab on clinical relapse in ANCA-associated vasculitis: identifying B cell biomarkers for relapse to guide retreatment decisions
  1. Md Yuzaiful Md Yusof1,2,
  2. Edward M Vital1,2,
  3. Sudipto Das1,2,
  4. Shouvik Dass1,2,
  5. Gururaj Arumugakani1,3,
  6. Sinisa Savic2,
  7. Andrew C Rawstron3,
  8. Paul Emery1,2
  1. 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK
  2. 2NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  3. 3Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  1. Correspondence to Professor Paul Emery, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK; p.emery{at}leeds.ac.uk

Abstract

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 naïve 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 naïve 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 naïve repopulation at 6 months, and 31% and 54% without naïve repopulation.

Conclusions Responses to B cell depletion therapy are long-lasting and relapse post-treatment may be predicted by absence of naïve B cell repopulation at 6 months. Naïve B-lymphopenia may be a biomarker of disease activity in AAV.

  • B cells
  • Cyclophosphamide
  • DMARDs (biologic)
  • Granulomatosis with polyangiitis
  • Systemic vasculitis

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