Systemic lupus erythematosus: management strategies

Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multisystem involvement and various phenotypes. It follows a relapsing-remitting course, marked by alternating periods of relative inactivity and disease flares that can lead to organ damage, significant morbidity, and increased mortality. Approximately half of patients with SLE develop organ damage within 5 years of diagnosis. Potentially modifiable risk factors for damage include uncontrolled disease activity/severe flares, and glucocorticoid exposure. This review outlines a strategy to reduce disease activity and prevent organ damage, emphasizing early diagnosis, maintenance of low disease activity with minimal corticosteroid use, and flare prevention. Early recognition is crucial to avoid disease progression and prevent the development of more severe phenotypes. The 2019 EULAR classification criteria strike a balance between specificity and sensitivity but exclude ANA-negative patients, who may represent up to 20% of cases at diagnosis. To address this limitation, we introduced the SLE Risk Probability Index (SLERPI), a simple, clinician-friendly, machine learning-based model that does not require ANA positivity as a criterion; a score > 7 in SLERPI has shown 94.2% accuracy. Reducing the frequency and severity of flares is a major treatment goal to prevent organ damage and achieve remission or maintain low disease activity. The 2023 EULAR recommendations suggest the early use of biological agents to control disease activity, reduce flares, and facilitate corticosteroid dose reduction and damage prevention. However, incomplete response or refractory disease remains a significant challenge for both patients and clinicians, with evidence suggesting that response rates decline with each subsequent flare. Globally, new approaches are being explored that target various cellular and molecular pathways, including B cells, T cells, and CAR-T cells. The use of CAR-T cell technology to profoundly deplete B cells has shown promising results.

Keywords

Systemic lupus erythematosus / disease activity / organ damage / flares / therapy discontinuation

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