Immunosuppressive and immunomodulatory therapies in Sjögren's disease: current landscape and future perspectives

Sjögren's disease (SjD) is a systemic autoimmune disorder primarily affecting exocrine glands alongside heterogeneous organ involvement. Historically managed through symptomatic relief and conventional disease-modifying therapies, recent immunological advances have steadily expanded our understanding of its pathogenesis and therapeutic approaches.

A systematic literature review regarding therapeutic agents for SjD treatment was conducted across the PubMed, Web of Science, Embase, and Cochrane Library databases.

Over the past two decades, significant advancements in immunology have profoundly deepened our understanding of SjD pathogenesis. This pathophysiological insight is facilitating a paradigm shift from conventional symptomatic relief toward targeted, phenotype-driven biological interventions. The therapeutic pipeline investigating novel agents - including B-cell depletion therapies, BAFF/APRIL pathway inhibitors, T-cell/B-cell interaction modulators (e.g. CD40-CD40L, CTLA-4), type I interferon blockade, and JAK-STAT inhibitors - is expanding rapidly. CAR-T cell therapy application in refractory SjD patients currently represents an emerging, strictly experimental approach requiring rigorous evaluation of safety and long-term feasibility. Ultimately, identifying the most effective therapeutic agents will likely require discovering and implementing biomarkers tailored to specific biological endotypes.