Precision medicine in SLE: where we are and where we are going

Abstract

Systemic lupus erythematosus (SLE) is heterogeneous in course and mechanism, demanding a shift from empirical therapy to pathway-guided, precision care. This review proposes a practical four-dimensional stratification—clinical/demographic, laboratory/serologic, biomolecular/multi-omics, and histologic/imaging—to map organ phenotypes to dominant immune pathways. We align treatments with these pathways, covering IFNAR blockade, BAFF-APRIL targeting, B-cell depletion/reprogramming, next-generation calcineurin inhibitors, complement inhibition, IL-12/23 modulation, abatacept, and low-dose IL-2, with emphasis on lupus nephritis combinations and steroid minimization. We advocate a monitoring paradigm that integrates conventional indices with pathway-anchored biomarkers, organ-specific readouts, and quantitative imaging, supported by interpretable artificial intelligence (AI) to set action thresholds at 8–12 weeks, 6 months, and 12 months. For clinical development, we recommend biomarker-enriched, adaptive platform trials using pathway-concordant composite endpoints and early surrogates. Key challenges include temporal shifts in biology, assay standardization, access and cost, real-world safety, and equity. Near-term priorities are lightweight standardized monitoring sets, organ-specific surrogate endpoints, and master protocols; longer-term opportunities in spatial/single-cell omics and causal AI aim to enable anticipatory, damage-sparing care.

Keywords

systemic lupus erythematosus / precision medicine / clinical trials

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Higher Education Press 2026

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