Journal Article10.1016/j.coi.2025.102578
Can we cure Sjogren’s disease? Unmet needs and raising questions in the era of Precision medicine
Loukas Chatzis,Andreas V. Goules,Athanasios G. Tzioufas +2 more
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Abstract: The wide spectrum of Sjögren's disease (SjD) clinical manifestations coupled with its multifaceted pathogenesis has complicated drug target development, optimal clinical trial design, identification of suitable SjD subgroups, selection of appropriate outcome measures, and interpretation of treatment efficacy. Despite recent advancements in biologic treatments for autoimmune diseases, the targeted therapy(ies) for SjD remain an unmet need, with no regulatory approvals, so far. Recent large, randomized studies have suggested some patient benefits; however, reproducibility is needed, and assessment of treatment efficacy requires refinement. In this review, we explore the potential for curing SjD taking into consideration the main pathogenetic mechanisms, clinical phenotypes, and underlying endotypes. We provide an overview of current recommendations and targeted treatments, identify potential reasons for treatment failures, and propose strategies (in and out of the box) for future directions. By addressing these areas, we offer a comprehensive perspective that may inform future research and therapeutic strategies for SjD.
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Advances in the diagnosis and treatment of Sjögren disease
Christos Tsironis,Asimina I. Karampela,Clio P. Mavragani,Christos Tsironis,Asimina I. Karampela +4 more
Abstract: Purpose of review Sjögren disease (SjD) constitutes a diagnostic and therapeutic challenge due to its clinical heterogeneity and complex pathophysiology. This review synthesizes recent advances in diagnostics, disease stratification, and targeted therapies, highlighting their potential to optimize patient care. Recent findings Emerging diagnostic approaches include advanced salivary, lacrimal, and serum biomarkers, refinements of established diagnostic tools, role of specific autoantibodies, and AI-assisted histopathology, improving early detection and risk stratification, particularly for lymphoma-prone phenotypes. Novel immunological insights have enabled phenotype-based classification, guiding the development of targeted therapies against B-cell pathways, cytokines, and co-stimulatory molecules with several agents (e.g., belimumab, ianalumab, telitacicept) showing promise in reducing disease activity scores. Summary Recent advances provide a framework for precision medicine in SjD, integrating molecular and imaging biomarkers into patient selection and treatment monitoring. Clinically, this could enable earlier diagnosis, individualized risk assessment, and tailored therapy. Research priorities now include validating diagnostic innovations in diverse populations, elucidating phenotype-specific mechanisms, and conducting adequately powered, biomarker-driven trials to optimize therapeutic efficacy.