The combined effects of iguratimod with anti-TNFα antibody on experimental arthritis models in mice

抄録

[Objectives] The combined effects of a new antirheumatic drug, iguratimod (IGU) with anti-tumor necrosis factor (TNF)α antibody (aTNFAb) were examined in two mouse models of arthritis.
[Methods] In collagen-induced arthritis (CIA) model, arthritis was induced by immunization with type II collagen on day 0 and 21. IGU was orally administrated once daily and aTNFAb was intraperitoneally injected twice a week from day 25 to day 34. In glucose-6-phosphate isomerase (GPI)-induced arthritis model, arthritis was induced by immunization with recombinant GPI on day 0 and the treatments were started on day 5. IGU was orally administrated daily and aTNFAb was intravenously injected every other day to day 14. Efficacy was evaluated using arthritis scores, articular destruction scores, and blood biochemical analyses.
[Results] In the CIA model, the combination of IGU and aTNFAb significantly inhibited the arthritis and articular destruction more effectively than as monotherapies. Serum interleukin (IL)-1β and IL-6 levels were also reduced significantly with combined treatment. The decline in serum levels of cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase (MMP)-3 was significantly enhanced with the IGU/aTNFAb combination. In the GPI-induced arthritis model, IGU and aTNFAb lowered the arthritis scores and the combination of both treatments showed a significant effect compared with IGU alone. Regarding anti-GPI titers on day 14, IGU and/or aTNFAb showed no significant effect.
[Conclusion] In the two mouse models, the combination of IGU and aTNFAb showed greater benefit than either monotherapy, suggesting such combination therapy would be effective in clinical use.