A data-driven, weighted flare score that accurately predicts organ damage in systemic lupus erythematosus

Nikolopoulos D, Pitsigavdaki S, Nöthling DM, Katechis S, Nikoloudaki M, Bergmann C, Silvagni E, Repa A, Ramming A, Marangoni A, Govoni M, Sidiropoulos P, Fanouriakis A, Boumpas D, Schett G, Bortoluzzi A, Garantziotis P, Bertsias G (2026)

Publication Type: Journal article

Publication year: 2026

Journal

DOI: 10.1016/j.ard.2026.06.013

Abstract

Objectives: Flares are key determinants of outcome in systemic lupus erythematosus (SLE), yet the conventional mild/moderate vs severe classification inadequately reflects prognosis. We sought to refine flare classification to improve damage prediction and develop a data-driven flare score. Methods: We analysed a multicentre longitudinal cohort of 354 patients with active SLE requiring treatment at inclusion (median follow-up 66 months). Flares were adjudicated using a modified Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index Flare Index (SFI). Random Forests and modified flare definitions assessed the contribution of individual SFI variables to subsequent damage. We derived a flare score using bootstrap-validated mixed-effects models. This was validated in an independent cohort (n = 110). Results: Both mild/moderate and severe SFI flares contributed to elevated 12-month damage risk (incidence rate ratio [IRR]:1.42 and 1.54, respectively). Among SFI subcriteria, major organ involvement requiring high-dose glucocorticoids (GCs) ranked highest for damage prediction (weight = 6), followed by the isolated GCs escalation criteria (weights = 1.5-3), whereas minor organ involvement and immunosuppressants/biologics addition carried lower weights (1 each). A flare score based on these subcriteria demonstrated good predictive performance (Brier score = 0.07). A threshold of ≥ 3.5 identified a subset of high-risk flares (40% of all episodes) that displayed the strongest association with subsequent damage (IRR: 2.49, 95% CI: 1.51-4.10) and outperformed the original SFI definition in the validation cohort (area under the curve–receiver operating characteristic: 0.893 vs 0.816). Although both Definitions of Remission in SLE (DORIS) and lupus low disease activity state correlated with lower risk of SFI-defined flares, only sustained DORIS (>50% of time) reduced high-risk flares. Conclusions: We defined and validated a novel weighted SLE flare score that better predicts damage accrual and may support treat-to-target implementation and clinical trial design.

Authors with CRIS profile

Involved external institutions

Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) University of Crete / Πανεπιστήμιο Κρήτης Greece (GR) Attikon Hospital / Πανεπιστημιακού Γενικού Νοσοκομείου "Αττικόν" Greece (GR) Azienda Ospedaliera Universitaria di Ferrara Arcispedale Sant'Anna Italy (IT)

How to cite

APA:

Nikolopoulos, D., Pitsigavdaki, S., Nöthling, D.-M., Katechis, S., Nikoloudaki, M., Bergmann, C.,... Bertsias, G. (2026). A data-driven, weighted flare score that accurately predicts organ damage in systemic lupus erythematosus. Annals of the Rheumatic Diseases. https://doi.org/10.1016/j.ard.2026.06.013

MLA:

Nikolopoulos, Dionysis, et al. "A data-driven, weighted flare score that accurately predicts organ damage in systemic lupus erythematosus." Annals of the Rheumatic Diseases (2026).

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