Can we cure Sjogren’s disease? Unmet needs and raising questions in the era of Precision medicine

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.