Use of advanced therapies in systemic lupus erythematosus: a retrospective single centre analysis based on disease...

To identify and analyse distinct subgroups of Systemic Lupus Erythematosus (SLE) based on serological and demographic profiles, and to assess their impact on clinical manifestations, disease activity, and use of advanced therapies.

We performed a cross-sectional analysis of a single-centre cohort of 327 SLE patients. Hierarchical cluster analysis was used to identify groups based on ten serological features: anti-dsDNA, anti-Sm, lupus anticoagulant, anti-cardiolipin, anti-B2GP1, hypocomplementemia, direct Coombs test, anti-Ro, anti-La, and anti-RNP. We further stratified patients by age of onset and sex.

The cohort was predominantly female (84.7%). Four serological clusters emerged: Cluster 1 (anti-Sm/RNP), Cluster 2 (aPL), Cluster 3 (anti-Ro/La), and Cluster 4 (dsDNA positive and ENA/aPL scarce). Cluster 1 (anti-Sm/RNP) was associated with the most severe phenotype, with higher rates of serositis (p = 0.001) and cutaneous manifestations (p = 0.006). These patients required multiple immunosuppressants (p = 0.01) and had the highest utilisation of biologics (p = 0.024). Conversely, Cluster 4 showed the lowest disease activity (p = 0.004) and highest rates of DORIS remission (p = 0.004). Notably, patients with late-onset SLE received significantly fewer biologics (11.1% vs. 35.5%, p < 0.001) and conventional immunosuppressants (68.5% vs. 83.2%, p = 0.013), yet they accrued greater cumulative organ damage (SDI >0: 70.4% vs. 52.4%, p = 0.015) compared to early-onset patients.

The anti-Sm/RNP signature identifies a severe, refractory phenotype, potentially necessitating intensified biologic therapy. Late-onset SLE represents a silent risk group, where lower treatment intensity correlates with higher damage accrual, suggesting current management strategies may be insufficient. These findings challenge the standard of care and support the implementation of serology-guided stratification.