Iguratimod (T-614): A novel disease modifying anti-rheumatic drug

Iguratimod is a small molecule compound with anti-inflammatory and immunomodulatory actions, which has been developed as a disease modifying anti-rheumatic drug (DMARD). Non-clinical studies of this compound revealed that inhibition of the production of immunoglobulins and various inflammatory cytokines mainly contributes to its improvement effect on various arthritis models in animals. In addition, iguratimod was found to possess anabolic effect on bone metabolism, through both stimulation of osteoblastic differentiation and inhibition of osteoclastgenesis. Regarding a more detailed mechanism of its action, the suppression of nuclear factor kappa B (NF-kB) activation without blocking NF-kB inhibitor a (IkBa) degradation has been indicated. Although the true target molecules of iguratimod have been unclear, it would be necessary to suppose the multiple mechanisms including suppression of NF-kB. Its effectiveness and tolerability comparable to salazosulfapyridine were examined by the clinical trials of Japanese patients with rheumatoid arthritis. Thus, iguratimod is a promising DMARD with novel properties and good clinical response. Further clinical study will clarify whether this drug is one of the useful options for treatment of patients who cannot use biologics.