Journal
NEPHROLOGY DIALYSIS TRANSPLANTATION
Volume 36, Issue 8, Pages 1408-1417Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfaa066
Keywords
ANCA; biomarkers; crescentic glomerulonephritis; immunomonitoring; rituximab; vasculitis
Categories
Funding
- Dutch Kidney Foundation [KJPB12.028, 17OKG04]
- Netherlands Organization for Scientific Research [90713460]
- FOREUM (systemic lupus erythematosus) project
- ARCH (ANCA-associated vasculitis)
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In AAV patients treated with RTX, ANCA and B-cell status were predictive of the majority of relapses, and specifically their absence strongly predicted a relapse-free status. Monitoring ANCA and B-cell levels could guide therapeutic decisions to prevent relapses in these patients.
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 >2years. Results. Patients (31/110) relapsed within 2years 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.
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