Abstract
Autoimmune diseases represent a growing global health concern, with a rising incidence and prevalence across the globe, and are expected to exponentially rise through 2050. This increase is attributed to factors such as urbanization, lifestyle changes, and improved healthcare access. Historically, the management of autoimmune and immune-mediated diseases has revolved around broad immunosuppression, primarily relying on corticosteroids and other disease-modifying agents. These have limitations such as non-specific immunosuppression, increased risk of infection, and end-organ damage. In subsequent years, the therapeutic armamentarium expanded to include biologic agents that selectively target individual pro-inflammatory cytokines, such as tumor necrosis factor (TNF) alpha inhibitors and anti-integrin or anti-interleukin-12/23 therapies. Although biologics have improved disease outcomes and enabled more targeted intervention, their use is constrained by factors such as immunogenicity, the need for parenteral administration, and a persistent risk of adverse effects, including serious infections and malignancy. These limitations have underscored the need for novel therapeutic modalities with improved efficacy, safety, and patient convenience. The advent of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) inhibitors has transformed the therapeutic landscape of immune-mediated diseases. Tofacitinib, upadacitinib, and filgotinib are orally administered small molecules that inhibit intracellular signaling of pro-inflammatory cytokines, which modulate several pathways simultaneously. In recent years, a therapeutic paradigm shift has emerged in the field of gastroenterology, with JAK inhibitors being increasingly utilized for the management of Inflammatory Bowel Disease (IBD). These have demonstrated efficacy in both induction and maintenance of remission, including among patients refractory to anti-TNF and other biologic therapies. This article will focus on the evolving role and paradigm shift in the use of JAK-STAT inhibitors from rheumatology to gastroenterology.