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Background <p>Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder characterized by synovial inflammation, cartilage degradation and progressive joint destruction. The pathogenesis of RA involves a complex interaction among immune cells, pro-inflammatory cytokines and dysregulated iron metabolism. Among the cytokines, interleukin-6 (IL-6) plays a pivotal role by activating JAK-STAT signaling pathway. This pathway is a central mediator of cytokine signaling, regulating immune responses, hematopoiesis and inflammation. Dysregulation of the JAK-STAT pathway promotes inflammation and joint damage in RA. Targeting this pathway has proven effective in slowing disease progression.</p> Aim of the work <p>To describe the immunopathological role of the JAK-STAT pathway in RA and summarize the therapeutic efficacy and safety of Janus kinase inhibitors (JAKi) in disease management.</p> Main body of abstract <p>Janus kinase inhibitors (JAKi) represent a novel class of oral targeted synthetic disease-modifying antirheumatic drugs (DMARDs) that block intracellular signaling of multiple cytokines. First-generation agents such as tofacitinib and baricitinib inhibit multiple JAK isoforms, while newer agents like upadacitinib and filgotinib offer greater selectivity, improved efficacy and safety. Clinical trials have demonstrated that JAKi reduce inflammation, slow radiographic progression, and improve physical function in patients unresponsive to conventional or biologic DMARDs. JAKi also modulate immune cell activation, suppress cytokine release, and inhibit fibroblast-like synoviocyte proliferation, contributing to long-term disease control.</p> Short conclusion <p>JAK inhibitors offer an effective oral therapeutic option for RA, improving clinical outcomes through cytokine pathway modulation. Despite their efficacy, JAKi carry safety concerns including increased risk of herpes zoster, thromboembolic events and cardiovascular complications.</p>

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The JAK-STAT pathway in rheumatoid arthritis: from mechanisms to JAK inhibitors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月6日

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  • Muhammad Saboor,
  • Salsabil Nesraoui,
  • Reem Abdulrab,
  • Sadia Babar,
  • Balqees Thabit

摘要

Background

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder characterized by synovial inflammation, cartilage degradation and progressive joint destruction. The pathogenesis of RA involves a complex interaction among immune cells, pro-inflammatory cytokines and dysregulated iron metabolism. Among the cytokines, interleukin-6 (IL-6) plays a pivotal role by activating JAK-STAT signaling pathway. This pathway is a central mediator of cytokine signaling, regulating immune responses, hematopoiesis and inflammation. Dysregulation of the JAK-STAT pathway promotes inflammation and joint damage in RA. Targeting this pathway has proven effective in slowing disease progression.

Aim of the work

To describe the immunopathological role of the JAK-STAT pathway in RA and summarize the therapeutic efficacy and safety of Janus kinase inhibitors (JAKi) in disease management.

Main body of abstract

Janus kinase inhibitors (JAKi) represent a novel class of oral targeted synthetic disease-modifying antirheumatic drugs (DMARDs) that block intracellular signaling of multiple cytokines. First-generation agents such as tofacitinib and baricitinib inhibit multiple JAK isoforms, while newer agents like upadacitinib and filgotinib offer greater selectivity, improved efficacy and safety. Clinical trials have demonstrated that JAKi reduce inflammation, slow radiographic progression, and improve physical function in patients unresponsive to conventional or biologic DMARDs. JAKi also modulate immune cell activation, suppress cytokine release, and inhibit fibroblast-like synoviocyte proliferation, contributing to long-term disease control.

Short conclusion

JAK inhibitors offer an effective oral therapeutic option for RA, improving clinical outcomes through cytokine pathway modulation. Despite their efficacy, JAKi carry safety concerns including increased risk of herpes zoster, thromboembolic events and cardiovascular complications.