High-sensitivity flow cytometry in rheumatoid arthritis shows that early B-cell subset depletion is linked to 5-year rituximab response, while failure to deplete B cells occurs early in subsequent poly-refractory disease.

Authors

Antonio Tonutti, Kerem Abacar, Paula David, Francesca Trunfio, Jacqueline L Nam, Richard Wakefield, Andrea Di Matteo, Md Yuzaiful Md Yusof, Benazir Saleem, Lesley-Anne Bissell, Shouvik Dass, Paul Emery, Edward Vital, Kulveer Mankia, Andy Rawstron, Dennis McGonagle

Published in

Annals of the rheumatic diseases. Aug 11, 2026. Epub Aug 11, 2026.

Abstract

To assess complete depletion of B-cell subsets using high-sensitivity flow cytometry (HSFC) across the therapeutic spectrum of rheumatoid arthritis (RA): from good initial rituximab (RTX) responders to poly-refractory RA (failed all biologic or targeted synthetic disease-modifying antirheumatic drug classes).
Single-centre real-world cohort of 232 RTX-treated RA adults undergoing peripheral blood HSFC assessment at baseline (before the first RTX infusion) and after 2 weeks (2W). Naïve, memory B cells and plasmablasts were quantified; complete depletion was defined as counts < 0.1 cells/µL. One-year response (simplified disease activity index ≤11 within 6 months, maintained for ≥ 12 months) and 5-year RTX persistence (maintained response with no therapeutic change for ≥ 5 years) were assessed. Longitudinal B-cell trajectories with multiple RTX cycles were analysed.
2W complete depletion rates were 91% for naïve, 92% for memory B cells, and 69% for plasmablasts. Higher 2W plasmablast counts were associated with lower odds of 1-year response (odds ratio [OR], 0.50; 95%CI, 0.32-0.75; P = .001) and 5-year RTX persistence (OR, 0.48; 95%CI, 0.30-0.79; P = .004); complete plasmablast depletion at 2W was positively associated with both outcomes. Early during disease, poly-refractory RA (n=31; 13%) showed higher 2W memory B-cell levels, and counts were associated with increasing refractoriness (OR, 1.9; 95%CI, 1.3-2.9; P = .003). Across multiple cycles, sustained suppression of memory B cells and plasmablasts were seen in patients showing RTX persistence.
2W plasmablast depletion on HSFC is strongly linked to 5-year RTX retention, while incomplete memory B-cell depletion characterises poly-refractory RA. Thus, responsiveness and refractoriness in RA are linked to B-cell pathology, endorsing HSFC implementation in selecting novel B-cell targeting strategies and early recognition of refractory disease.

PMID:
42580905
Bibliographic data and abstract were imported from PubMed on 12 Aug 2026.

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