According to a recent article published in the International Immunopharmacology, the combined application of tofacitinib and iguratimod may have a greater therapeutic effect on refractory rheumatoid arthritis (RRA) and its associated osteoporotic bone remodeling. In the rat model of collagen-induced arthritis (CIA) + tumor necrosis factor (TNF), the use of tofacitinib and iguratimod showed significant improvement in reducing joint inflammation, bone erosion, and pyroptosis associated with RRA.
Dr. Chen and colleagues created an in vivo collagen-induced arthritis (CIA) model by continuously injecting TNF-α to exacerbate active rheumatoid arthritis (RA) and secondary osteoporosis. The CIA + TNF model also effectively induced bone damage, significant inflammatory cell infiltration, and synovial hyperplasia, as well as high levels of IL-6, IL-1β, and IL-18, which may resemble the clinical symptoms observed in individuals with active RA. The study involved 40 male Sprague-Dawley rats randomly assigned to five groups: normal controls, CIA + TNF model, tofacitinib treatment (TOF), iguratimod treatment (IGU), and TOF + IGU combination treatment group. The levels of interleukin (IL)-18, IL-1β, and IL-6 in the plasma were noticeably elevated in the CIA + TNF model and significantly reduced in the combination group following treatment with TOF and/or IGU. Additionally, arthritic scores and inflammatory cell infiltration in synovial tissues were reduced. In vitro results showed a persistent trend towards a considerable decrease in the expression of pyroptosis-related proteins in the combination group compared to the CIA + TNF group. Furthermore, compared to the CIA + TNF model, bone destruction was considerably reduced, and the rate of bone turnover was noticeably higher in the combination group.
According to a study conducted by Du et al., the administration of IGU at doses of 5 mg/kg daily and 20 mg/kg daily significantly reduced arthritis scores in a collagen-induced arthritis (CIA) model. Furthermore, combining IGU at a dose of 10 mg/kg daily with MTX almost completely suppressed arthritis progression. Another study by Adam et al. found that TOF had protective effects against bone loss caused by ovariectomy and CIA in mice. In these models, TOF decreased the ratio of receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) to osteoprotegerin (OPG) in serum and increased bone mass.
The concurrent use of TOF and IGU may potentially offer added therapeutic benefits for treating RRA and secondary osteoporotic bone remodeling in patients who do not respond well to existing treatments. Additional clinical research can confirm the findings of this study and contribute to improving patient care for RA.
References
- Chen J, Che Q, Kou Y, Rong X, Zhang X, Li M, et al. A novel drug combination of Tofacitinib and Iguratimod alleviates rheumatoid arthritis and secondary osteoporosis. Int Immunopharmacol. 2023 Sep 15;124(Pt B):110913.
- Du F, Lü L jing, Fu Q, Dai M, Teng J lin, Fan W, et al. T-614, a novel immunomodulator, attenuates joint inflammation and articular damage in collagen-induced arthritis. Arthritis Res Ther. 2008;10(6):R136.
- Adam S, Simon N, Steffen U, Andes FT, Scholtysek C, Müller DIH, et al. JAK inhibition increases bone mass in steady-state conditions and ameliorates pathological bone loss by stimulating osteoblast function. Sci Transl Med. 2020 Feb 12;12(530):eaay4447.