TOPLINE

Complete depletion of memory B cells and plasmablasts within 2 weeks of rituximab infusion was associated with clinical response in patients with idiopathic inflammatory myopathies (IIM),and highly sensitive flow cytometry (HSFC) detected these differences, while conventional flow cytometry did not.

METHODOLOGY

• Researchers conducted a single-center, retrospective cohort study in the United Kingdom, including 44 adults  (median age, 45 years) with IIM who were treated with rituximab between January 2015 and December 2025.
• Overall, 24 patients with dermatomyositis, 12 with antisynthetase syndrome, five with immune-mediated necrotizing myositis, and three with polymyositis were included.
• HSFC was performed at baseline and at 2 weeks after rituximab infusion to measure naive B cells, memory B cells, and plasmablasts, using a cutoff of <0.1 cells per μL for complete depletion vs the conventional flow cytometry cutoff of <5 total B cells per μL.
• The primary outcome was clinical response, defined as at least moderate improvement on the 2016 the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) total improvement score at a median of 4 months after infusion. 
• Secondary outcome was subsequent relapse.

TAKEAWAY

• Clinical response occurred in 31 (70%) patients; responders achieved a significantly higher median total improvement score compared with non-responders (50.0 vs 17.5; P < .0001).
• At 2 weeks, complete plasmablast depletion was significantly more frequent in responders than non-responders (94% vs 31%; P < .0001). 
• Higher 2-week plasmablast counts were associated with lower odds of subsequent response (odds ratio [OR], 0.03; P = .0002), whereas complete depletion of memory B cells (OR, 8.68; P = .038) and plasmablasts (OR, 25.20; P < .0001) was associated with response. The conventional flow cytometry cutoff showed no association with treatment response.
• At a median of 12 months, 59% of 27 responders relapsed. Among patients who relapsed, only 6% still had complete naive B-cell depletion, compared with 46% among those who did not relapse (P = .027).

IN PRACTICE

"Although these findings require prospective validation, combining HSFC-defined minimal residual disease assessment with autoantibody profiling could help to uncover the pathogenic B-lineage programs underlying myositis immunopathology across disease subsets and provide a valuable framework for precision selection and escalation of more potent B-cell depletion strategies in patients who do not respond or who relapse," the authors wrote.

SOURCE

The study was led by Antonio Tonutti, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom. It was published online on August 27 in The Lancet Rheumatology.

LIMITATIONS

The study's retrospective, single-center design and relatively small sample size may limit generalizability. Inclusion of only patients with HSFC data could have introduced selection bias.

DISCLOSURES

The study was supported by Leeds National Institute of Health Research Biomedical Research Centre. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.