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TOPLINE:

More than 50% of patients with systemic lupus erythematosus (SLE) experienced flare and nearly 50% had persistently active disease, whereas some had persistently active disease without flare. Both conditions were linked to a greater risk for organ damage accrual.

METHODOLOGY:

• Researchers analyzed data of a multinational observational cohort, including 3811 adults with SLE (median age at diagnosis, 29 years; 92.1% women) enrolled between March 2013 and December 2020, to identify the frequency and determinants of flare and persistently active disease.
• The patients received treatment under standard care conditions and were followed up every 3-6 months, with a median follow-up duration of 2.8 years.
• The following definitions were used to assess the disease status:
  • Flare : Defined using the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)
  • Persistently active disease: A SLEDAI-2000 score ≥ 4 on two or more consecutive visits with an interval of 6 months or less, excluding cases with serologic activity alone
  • Damage accrual: Any increase in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index
  • Lupus low disease activity state: A SLEDAI- 2000 score ≤ 4, no activity in major organs, no new disease activity since the last assessment, and standard doses of medications
• A predictive model for flare and persistently active disease was developed and was validated in a subset of patients.

TAKEAWAY:

• Over the follow-up period, 56.2% of patients experienced flare, and 46.9% had persistently active disease; notably, 9.7% experienced persistently active disease without flare, and 37.2% experienced both.
• Both flare and persistently active disease were associated with an increased risk for damage accrual (adjusted odds ratio [aOR], 1.29; P = .021 and aOR, 1.55; P < .001, respectively).
• Predictors of subsequent flare included low gross domestic product in country of residence, smoking, renal activity, arthritis, low complement levels, and the use of mycophenolate mofetil/mycophenolic acid during the first 3 years (P < .05 for all). Renal activity and time-adjusted mean SLEDAI-2000 score were predictors of persistently active disease (P < .001 for both).
• Achieving a lupus low disease activity state for ≥ 50% of the follow-up time had a significant protective effect against the subsequent development of both conditions. Moreover, the predictive model correctly classified 72.1% of flares (area under the receiver operating characteristic [ROC] curve, 0.74) and 83.8% of persistently active disease (area under the ROC curve, 0.88).

IN PRACTICE:

“The high frequency of PAD [persistently active disease] and its negative impact on patient outcomes make a compelling case for its use as a clinically meaningful endpoint,” the authors of the study wrote. “Our predictive models may help identify patients at high risk of flare or PAD to target for more stringent follow-up and assist in selecting high-risk patients for clinical trials.”

SOURCE:

This study was led by Yanjie Hao, MD, University of Melbourne and St Vincent’s Hospital Melbourne, both in Melbourne, Australia, and Peking University First Hospital in Beijing, China. It was published online on February 26, 2025, in ACR Open Rheumatology.

LIMITATIONS:

The SLEDAI-2000 score used to define persistently active disease may have omitted several clinical manifestations while potentially overestimating its frequency. The findings suggested an association and not causation. The use of rituximab and belimumab was limited, and information on the use of anifrolumab and ciclosporin was lacking.

DISCLOSURES:

The Asia Pacific Lupus Collaboration received grants from several sources, including AstraZeneca, Bristol Myers Squibb, and Eli Lilly. One author reported receiving a research scholarship from the University of Melbourne, and another author reported receiving support in part from a research program through the National Research Foundation of Korea. Two other authors reported receiving grants from the National Health and Medical Research Council.

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