Evolving treatments for Sjögren disease: current approaches and emerging targets

Sjögren disease (SjD) is a prevalent systemic autoimmune condition characterised by exocrine gland dysfunction, systemic inflammation and heterogeneous organ involvement. Current management remains largely symptomatic, with no approved disease-modifying therapies available and substantial unmet clinical need. However, advances in understanding immunopathogenesis have accelerated the development of targeted treatments. Ianalumab, a dual-acting B cell-activating factor receptor (BAFF) receptor inhibitor with B cell-depleting activity, is the first agent to report positive phase 3 results, showing significant improvements in systemic disease activity. Other investigational approaches include BAFF/APRIL pathway inhibition, T-cell-B-cell costimulation inhibition, type I interferon blockade, JAK-STAT, TYK2 and BTK inhibition, neonatal Fc receptor antagonist and endosomal Toll-like receptor inhibition, with exploratory modalities such as RNA-targeted agents and cellular immunotherapy (including Chimeric antigen receptor T therapy) under evaluation for severe or refractory disease. Outcome assessment has also evolved, with European Alliance of Associations for Rheumatology (EULAR) Sjögren Syndrome Disease Activity Index and EULAR Sjögren Syndrome Patient Reported Index providing validated physician- and patient-centred measures. Composite endpoints such as the Composite of Relevant Endpoints for Sjögren Syndromeand the Sjögren Tool for Assessing Response now integrate systemic, symptomatic and functional domains, improving sensitivity and feasibility in trials. Together, these tools support more rigorous evaluation of novel therapies. Overall, therapy in SjD is shifting towards precision, phenotype-informed strategies. Priorities now are confirming long-term safety and durability of response, and demonstrating patient-important benefit. In Australia, the impact of new therapies for SjD will hinge on clear diagnostic pathways, routine use of validated disease activity measures and multidisciplinary care models.