Repeat cycles of rituximab on clinical relapse in ANCA-associated vasculitis: identifying B cell biomarkers for relapse to guide retreatment decisions. Issue 9 (8th April 2015)

• Record Type: Journal Article
• Authors: Md Yusof, Md Yuzaiful; Vital, Edward M; Das, Sudipto; Dass, Shouvik; Arumugakani, Gururaj; Savic, Sinisa; Rawstron, Andrew C; Emery, Paul
• Is Part Of: Annals of the rheumatic diseases. Volume 74:Issue 9(2015)
• Page Start: 1734
• Page End: 1738
• Publication Date: 2015-04-08
• Subjects: B cells -- Cyclophosphamide -- DMARDs (biologic) -- Granulomatosis with polyangiitis -- Systemic vasculitis; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-206496
• Languages: English
• ISSNs: 0003-4967

Abstract

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.