title: Repeat cycles of rituximab on clinical relapse in ANCA-associated vasculitis: identifying B cell biomarkers for relapse to guide retreatment decisions.
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.
authors: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Md Yuzaiful
authors: MY
authors: Md Yusof
authors: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Edward M
authors: EM
authors: Vital
authors: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Sudipto
authors: S
authors: Das
authors: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Shouvik
authors: S
authors: Dass
authors: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Gururaj
authors: G
authors: Arumugakani
authors: NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Sinisa
authors: S
authors: Savic
authors: Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Andrew C
authors: AC
authors: Rawstron
authors: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Paul
authors: P
authors: Emery
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019233:Retreatment; D012189:Retrospective Studies; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D015415:Biomarkers; D000069283:Rituximab; D002097:C-Reactive Protein
keywords: B cells; Cyclophosphamide; DMARDs (biologic); Granulomatosis with polyangiitis; Systemic vasculitis