Trial reportRheumatology (Oxford, England)2025
Unsupervised machine learning identifies distinct SLE patient endotypes with differential response to belimumab.
Trial report in Rheumatology (Oxford, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed.
- Artificial Intelligence and Machine Learning in Rheumatology and Systemic Inflammatory Diseases: From Pattern Recognition to Signal Analysis and Clinical Decision Support.Journal of clinical medicine · 2026Review
- Cardiometabolic Candidate Endotypes in Psoriatic Disease: Integration of Clinical, Metabolic, and Immunogenetic Data Across Psoriasis and Psoriatic Arthritis.Life (Basel, Switzerland) · 2025Article
- Lessons Learnt from the Belimumab Trials in Systemic Lupus Erythematosus.International journal of molecular sciences · 2025Review
- Artificial Intelligence in Rheumatology: Quo Vadis?Mediterranean journal of rheumatology · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
Abstract
objectiveTo determine SLE endotypes according to B cell immunophenotyping and serological profile and assess endotypes' response to belimumab.
methodsWe analysed data from 796 patients with SLE from the phase III trial BLISS-SC. Unsupervised machine learning employing factor analysis of mixed data (FAMD) and subsequent clustering determined endotypes based on B cell immunophenotyping and serological profiles. Cox regression was used to assess belimumab efficacy on inducing lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS) remission within clusters.
resultsThree endotypes were determined. Compared with each other, cluster 1 (n = 191) displayed higher proportions of CD19+CD24b+CD27+ regulatory B cells (mean ± SD: 35.9%±12.6%), CD19+CD20+CD27+ bulk memory B cells (32.2%±9.9%), CD19+CD20+CD69+ activated B cells (0.2%±0.3%), CD19+CD20-CD138+ long-lived plasma cells (0.7%±1.0%) and CD19+CD38b+CD27b+ SLE-associated plasma cells (6.6%±7.0%). Cluster 2 (n = 366) displayed higher proportions of CD19+CD24bbrightCD38bbrightCD27- transitional B cells (6.3%±9.0%) and CD19+CD20+CD27- naïve B cells (85.4%±7.2%), and lower proportions of CD19+CD20-CD138+ peripheral long-lived plasma cells (0.2%±0.3%) and CD19+CD38b+CD27b+ SLE-associated plasma cells (1.6%±2.0%). Cluster 3 (n = 239) displayed a higher proportion of CD19+CD20+CD138+ short-lived plasma cells (0.1%±0.1%) and higher serological activity, being enriched in anti-double stranded(ds)DNA, anti-ENAs, antiphospholipid antibodies and hypocomplementemia. Use of belimumab was superior to placebo in inducing sustained LLDAS [hazard ratio (HR): 2.22; 95% CI: 1.18-4.17; P = 0.014] and DORIS remission (HR: 3.45; 95% CI: 1.2-9.94; P = 0.022) in cluster 2.
conclusionThree distinct SLE endotypes were identified based on B cell immunophenotyping and serological profiles, showing differential benefit from belimumab therapy.
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