Iguratimod for the treatment of rheumatoid arthritis in Japan

Abstract

Iguratimod (IGU), a small-molecule compound, was developed as a disease-modifying antirheumatic drug in Japan. The pharmacological studies showed that inhibition of the production of cytokines and immunoglobulins mainly contributes to its improvement effect on animal arthritis models. The first clinical study of IGU in Japanese patients with rheumatoid arthritis was started in 1992 and Phase III studies were started in 1998. From the results of Phase II studies, a dose-escalating regimen was recommended to relieve the side effects. In a double-blind study comparing the efficacy and safety of the drug with those of placebo and salazosulfapyridine, it was confirmed that IGU was superior to placebo and was not inferior to salazosulfapyridine. Furthermore, a double-blind controlled trial of IGU in combination with methotrexate revealed an efficacious and manageable safety profile. IGU would be widely used as a new option for rheumatoid arthritis treatment and combination drug with methotrexate.

Keywords:

• DMARD
• iguratimod
• rheumatoid arthritis
• T-614

Financial & competing interests disclosure

The authors were supported by Toyama Chemical Co., Ltd. and Eisai Co., Ltd. K Tanaka and T Yamaguchi are employees of Toyama Chemical Co., Ltd. M Hara served for consultancy to Eisai Co., Ltd. and Toyama Chemical Co., Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Iguratimod (IGU) is an oral active small-molecule compound that was approved as a disease-modifying antirheumatic drug in Japan.

• IGU inhibits production of inflammatory cytokines and immunoglobulins through suppression of NF-κB activation.

• The studies on action mechanism of IGU are ongoing, and it is expected that a molecular target of this drug will become clear sometime soon.

• From the results of Phase II studies, a dose-escalating regimen, in which a daily dose of IGU was kept at 25 mg for the first 4 weeks and 50 mg for subsequent treatment, was recommended to reduce side effects.

• In a double-blind study to compare efficacy and safety of the drug with those of placebo and salazosulfapyridine, it was confirmed that IGU was superior to placebo and was not inferior to salazosulfapyridine.

• A double-blind controlled trial of IGU in combination with methotrexate revealed an efficacious and manageable safety profile.

• Dose-related increases in the number of adverse events were observed in the clinical trials. Common adverse events included gastrointestinal disorders (upper abdominal pain, stomatitis), liver abnormalities, anemia and increased blood urea.

• IGU would become a new option for the treatment of rheumatoid arthritis and the combination drug with methotrexate.

• IGU is under all-case surveillance and early post-marketing phase vigilance and the clinical positioning of IGU would become clearer because usability analyses of the monotherapy and the combination with other synthetic or biological disease-modifying antirheumatic drugs will be examined.

Notes