The Main Challenges in Systemic Lupus Erythematosus: Where Do We Stand?

Abstract

Systemic lupus erythematosus (SLE) is an immune-mediated multi-systemic disease characterized by a wide variability of clinical manifestations and a course frequently subject to unpredictable flares. Despite significant advances in the understanding of the pathophysiology and optimization of medical care, patients with SLE still have significant mortality and carry a risk of progressive organ damage accrual and reduced health-related quality of life. New tools allow earlier classification of SLE, whereas tailored early intervention and treatment strategies targeted to clinical remission or low disease activity could offer the opportunity to reduce damage, thus improving long-term outcomes. Nevertheless, the early diagnosis of SLE is still an unmet need for many patients. Further disentangling the SLE susceptibility and complex pathogenesis will allow to identify more accurate biomarkers and implement new ways to measure disease activity. This could represent a major step forward to find new trials modalities for developing new drugs, optimizing the use of currently available therapeutics and minimizing glucocorticoids. Preventing and treating comorbidities in SLE, improving the management of hard-to-treat manifestations including management of SLE during pregnancy are among the remaining major unmet needs. This review provides insights and a research agenda for the main challenges in SLE.

Keywords: damage; disease activity; glucocorticoids; review; systemic lupus erythematosus.

Figure 1

Overview of the main unmet needs in the field of Systemic Lupus Erythematosus (SLE).

Figure 2

A hypothetical example illustrating how an integrated clinical and OMICS approach, driven by artificial intelligence, might help distinguishing homogeneous clusters from current heterogeneous phenotypes observed in Systemic Lupus Erythematosus (SLE). The example suggests that the way to identify new clusters with specific disease biomarkers should be tailored to the specific molecular events or pathways associated with disease activity and clinical phenotypes, providing a rationale for personalized therapeutic interventions.