Research Article
Qiang Xu
Abstract
Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic synovial inflammation and disability. The most widely used Disease-Modifying Antirheumatic Drug (DMARD) is methotrexate and it continues to be the gold standard. However, the use of high-dose methotrexate is associated with severe adverse effects. Iguratimod, which is currently used in clinics in China and Japan, is a novel oral DMARD for the treatment of RA. In this study, the effect of combination of methotrexate and iguratimod on murine Collagen-Induced Arthritis (CIA) and its mechanism was determined. Oral administration of iguratimod (3 mg/kg, 10 mg/kg) combined with methotrexate (1 mg/kg) potently blocked CIA development and delayed its progression, which was stronger than iguratimod or methotrexate used alone. Furthermore, infiltration of inflammatory cells into the synovium was remarkably inhibited by combination therapy and importantly, no bone erosion and joint destructions were observed in combination therapy group. In addition, combined administration of these two DMARDs suppressed production of cytokines (IL-17, IFN-γ, IL-6 and TNF-α) and antibodies (IgG and IgG2b) in serum, as well as humoral and cellular responses in CIA mice. Consistent with its effects in vivo, iguratimod combined with methotrexate significantly suppressed T and B cells responses in vitro. Taken together, our findings suggest that combination treatment with iguratimod and methotrexate should be an intriguing and preferable therapeutic strategy for treating RA.