POS1015 A NOVEL DRUG COMBINATION OF IGURATIMOD AND TOFACITINIB ALLEVIATES RHEUMATOID ARTHRITIS AND SECONDARY OSTEOPOROSIS

Background At present, specific immune targeted therapeutics including biologics and kinase inhibitors has made significant progress in Rheumatoid arthritis (RA). However, the irresponse to therapies some refractory RA patients suggests more attention should be paid on cell death pathways, such as pyroptosis. TNF-α is a proinflammatory cytokine that plays fundamental role pathogenesis of RA, which could induce pyroptosis monocytes macrophages cause destruction bone cartilage. Iguratimod (IGU) been confirmed highly efficacious safe conventional synthetic disease-modifying anti-rheumatic drug for Asia. Whether combination IGU Tofacitinib (TOF), Janus inhibitor, would better partner need elucidated. Objectives To evaluate therapeutic effect TOF active secondary osteoporosis collagen-induced (CIA)+TNF model. Methods In this study, hematoxylin eosin (HE) staining were used pathological changes ankle joints CIA+TNF Immunohistochemistry (IHC) level related proteins synovial tissue. We performed Micro-computed tomography (Micro-CT), HE IHC analyze trabecular distal femoral metaphyses investigate knee joint. Results After 6 weeks treatment and/or TOF, diameter joint interleukin (IL)-18, IL-1 M group. showed only small amount inflammatory infiltration less pannus seen tissue both monotherapy group, when compared with Of importance, proteins, gasdermin D (GSDMD), nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), caspase-1, IL-1β significantly expression group Both osteoblast formation osteoclast absorption sharply ruined However was alleviated turnover rate remarkably increased detected by Micro-CT, IHC. Conclusion The TOF-IGU synergistically disease severity CIA model, relieving inflammation erosion, suppressing activation NLRP3 inflammasome reducing GSDMD-mediated combined application may have stronger remodeling. Figure 1. Therapeutic effects (A) joint; (B) tissue; (C) (D) Micro-CT analysis femurs; (E) (F) ALP TRAP Acknowledgements ECCM Program Clinical Research Center Shandong University (No. 2021SDUCRCB010) Natural Science Foundation Province (ZR2022MH177) Disclosure Interests None Declared.