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

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