PR3-ANCAs predict relapses in ANCA-associated vasculitis patients after rituximab. Issue 8 (30th June 2020)

• Record Type: Journal Article
• Authors: van Dam, Laura S; Dirikgil, Ebru; Bredewold, Edwin W; Ray, Argho; Bakker, Jaap A; van Kooten, Cees; Rabelink, Ton J; Teng, Yoe K Onno
• Is Part Of: Nephrology dialysis transplantation. Volume 36:Issue 8(2021)
• Page Start: 1408
• Page End: 1417
• Publication Date: 2020-06-30
• Subjects: ANCA -- biomarkers -- crescentic glomerulonephritis -- immunomonitoring -- rituximab -- vasculitis; Nephrology -- Periodicals; Hemodialysis -- Periodicals; Kidneys -- Transplantation -- Periodicals; Hemodialysis; Kidneys -- Transplantation; Nephrology; Periodicals; 616.61
• DOI: 10.1093/ndt/gfaa066
• Languages: English
• ISSNs: 0931-0509

Abstract

Abstract: Background. The primary challenge of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patient care is the early detection of relapses to prevent organ damage and increase survival. Potential biomarkers for relapses are ANCA and B cells, but their predictive value is a matter of debate. Therefore this study investigated how ANCA and B-cell status related to relapses in AAV patients treated with rituximab (RTX) as remission induction (RI). Methods. This single-centre cohort study identified 110 ANCA-positive AAV patients treated with RTX between 2006 and 2018. Serial ANCA, CD19 + B-cell status and relapses were assessed >2 years. Results. Patients (31/110) relapsed within 2 years after RTX RI treatment. Patients who achieved and maintained PR3-ANCA negativity ( n = 29) had few relapses (3%), while persistent proteinase 3 (PR3)-ANCA positivity ( n = 49) and reappearance of PR3-ANCAs ( n = 10) associated significantly with more relapses (37%, P = 0.002 and 50%, P = 0.002). Patients with incomplete B-cell depletion ( n = 11) had significantly more relapses (54%) as compared with patients with B-cell depletion [ n = 76 (26%), P = 0.02]. Also, patients with repopulation of B cells ( n = 58) had significantly more relapses (41%) as compared with patients without B-cell repopulation [ n = 27 (15%), P = 0.03]. Overall, the absence of PR3- or myeloperoxidase (MPO)-ANCA positivity was highly predictive for remaining relapse-free. In PR3-ANCA-positive patients, 96% of the relapses occurred with persistent or reappearance of PR3-ANCAs and 81% with B-cell repopulation. In MPO-ANCA-positive patients, all relapses were restricted to patients with persistent MPO-ANCAs and B-cell repopulation. Conclusions. Upon RI treatment with RTX in AAV patients, ANCA and B-cell status were predictive of the majority of relapses and specifically their absence strongly predicted a relapse-free status. Therefore the implementation of ANCA and B-cell monitoring could guide therapeutic decision-making to prevent relapses in AAV patients treated with RTX.