TOPLINE

A weighted flare score based on features such as organ involvement and glucocorticoid escalation identified high-risk flares in patients with active systemic lupus erythematosus (SLE). 

METHODOLOGY

• Researchers conducted a multicenter retrospective cohort study including 354 patients aged 16 years or older (92.5% female individuals) with active SLE and an SLE Disease Activity Index (SLEDAI) 2000 score ≥ 6 and/or a Physician Global Assessment score ≥ 1.5 at baseline from January 2008 to June 2018.
• Flares were adjudicated using a modified Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI Flare Index (SFI), with individual subcriteria assessed for contribution to subsequent damage using Random Forests and bootstrap-validated mixed-effects models.
• A weighted flare score was derived based on the subcriteria most strongly associated with organ damage accrual, assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score, and incidence of new damage was evaluated within 12 months following flare episodes.
• The analysis identified new or worsened major organ manifestations requiring glucocorticoid intensification and the addition of immunosuppressants or biologics as the most influential severe flare components, and new or worse clinical manifestations and increased or added glucocorticoids ranked highest for mild-to-moderate flares.
• An external validation was performed in an independent cohort of 110 patients with SLE, observed over a median of 66.3 months, to assess the prognostic performance of the derived weighted flare score.

TAKEAWAY

• The cumulative probability of mild-to-moderate flares reached 23.8%, 43.6%, and 55.6% at 12, 24, and 36 months, respectively, and severe flares occurred at 18.3%, 28.2%, and 34.6% at the corresponding timepoints.
• Following flare-free visits, new organ damage developed at a rate of 12.9 per 100 person-years (95% CI, 11.3-14.7), and this rate rose to 19.3 (95% CI, 14.6-25.0) per 100 person-years after mild-to-moderate flares and to 25.4 (95% CI, 19.6-32.4) per 100 person-years after severe flares.
• Overall, 40.6% of flare episodes were high-risk flares (weighted score ≥ 3.5). An increasing number of high-risk flares were linked to a progressive increase in the risk for damage accumulation (incidence rate ratio for five or more events, 2.49; 95% CI, 1.51-4.10). The high-risk flare score outperformed conventional SFI definitions in the validation cohort (area under the receiver operating characteristic curve, 0.89 vs 0.82).
• Experiencing sustained Definition of Remission in SLE (DORIS) remission for more than 25% of the first year was associated with a reduced risk for subsequent high-risk flares (hazard ratio, 0.54; 95% CI, 0.34-0.85).

IN PRACTICE

“[The study] findings suggest that sustained DORIS remission, rather than intermittent low disease activity, may be needed to meaningfully reduce the occurrence of high-risk flares and subsequent organ damage,” the authors wrote.

SOURCE

The study was led by Dionysis Nikolopoulos, MD, PhD, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. It was published online on July 3, 2026, in Annals of the Rheumatic Diseases.

LIMITATIONS

Patient recruitment from tertiary referral centers likely resulted in a cohort enriched with more severe and treatment-resistant cases. The cohort consisted almost exclusively of White patients with modest representation of severe renal involvement, which may restrict applicability to more diverse populations. Scheduled visit-based observational design may have incompletely captured self-limiting mild-to-moderate flares. Laboratory results obtained within 30 days of the clinical assessment may have caused a mismatch between serologic and clinical activity measurements.

DISCLOSURES

This study received funding from the Research Account of the University of Crete and the Pancretan Health Association. One author disclosed receiving grants from the Swedish Rheumatism Association, King Gustaf V’s 80-Year Foundation, and the Ulla and Roland Gustafsson Foundation. Some authors reported receiving consulting fees or honoraria, fees for lectures, and/or grants from various companies including AstraZeneca, GSK, Lilly, and others.

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