Iguratimod at the EULAR 2012

Iguratimod (T-614) is a novel disease modifying anti-rheumatic drug (DMARD). Iguratimod is characterized by inhibitory effects on immunoglobulin production in B cells as well as inhibiting cytokine production. Its' mode of action comes by suppression of nuclear factor kappa B (NF-kB) activation. Another source gives the following data on pharmacology: “novel disease modifying anti-rheumatic drug (DMARD) - selective inhibitor of cyclo-oxygenase-2 (COX-2), and inhibits the production of interleukin-1 (IL-1), IL-6, IL-8 and tumour necrosis factor” (http://www.ukmi.nhs.uk/applications/ndo/record_view_open.asp?newDrugID=5488). Efficacy and tolerability are comparable to salazosulfapyridine (Keiichi Tanaka: http://www.pagepress.org/journals/index.php/rr/article/view/rr.2009.e4). A “long-term safety study of iguratimod in patients with rheumatoid arthritis” by M. Hara and colleagues has already been published in 2007 (Mod Rheumatol. 2007;17(1):10-6. Epub 2007 Feb 20 / http://www.ncbi.nlm.nih.gov/pubmed/17278016). The drug has only been studied in Japan so far, but remember where tocilizumab comes from.


Let´s move to the EULAR 2012 in Berlin.
M. Mikami and colleagues presented a study … on mice. Rats, I thought we’re already past this! It shows what has already been published in humans. OK I’m not fond of animal testing, but presented like this, no … it must be old unpublished material.


[AB0175] THE COMBINED EFFECTS OF IGURATIMOD, A NOVEL DMARD, AND METHOTREXATE ON ADJUVANT-INDUCED ARTHRITIS AND COLLAGEN-INDUCED ARTHRITIS
M. Mikami, H. Murao, J. Funaki, K. Tanaka. Research Laboratories, Toyama Chemical Co., Ltd., Toyama, Japan
Conclusions: Our results suggest that the combination of iguratimod with MTX would demonstrate beneficial effects in RA patients. The switch of MTX to iguratimod could ameliorate the disease in RA patients with inadequate response to MTX.


Let’s give it another try! H. Murao and colleagues found that iguratimod inhibits osteoclastogenesis and bone resorption IN VITRO. “Murine RAW264.7 cells and primary osteoclast precursor monocytes derived from mouse bone marrow (BMMs) were used for experiments.” Not what I was looking for, but knowing this could be useful.


[AB0124] IGURATIMOD, A NOVEL DMARD, INHIBITS OSTEOCLASTOGENESIS AND BONE RESORPTION IN VITRO
H. Murao1, M. Mikami1, J. Funaki1, K. Muramoto2, K. Tanaka1. 1Research Laboratories, Toyama Chemical Co., Ltd., Toyama; 2Tsukuba Research Laboratories, Eisai Co., Ltd, Tsukuba, Japan
Conclusions: Iguratimod showed the inhibitory effects on osteoclastogenesis and bone resorption via the suppression of NFATc1 expression without blocking the cell proliferation, unlike other DMARDs. These results suggest that such action would contribute to the clinical effect on articular destruction in patients with RA.


You’ve waited long enough! There is indeed some interesting study waiting for you. M. Hara and colleagues presented a study on efficacy and safety of iguratimod in combination with methotrexate in rheumatoid arthritis patients with inadequate response to methotrexate. The study is a multi-center, double-blind, placebo controlled phase2/3 study over a period of 52 weeks. 165 patients on verum were compared to 88 patients on placebo. The methotrexate dose has been rather low with 6-8 mg per week. Look for results and conclusions:


[OP0205] EFFICACY AND SAFETY EVALUATION OF IGURATIMOD, A NOVEL ANTI-RHEUMATIC AGENT – A DOUBLE-BLIND, COMPARATIVE STUDY OF IGURATIMOD-MTX COMBINATION IN RHEUMATOID ARTHRITIS PATIENTS WITH AN INADEQUATE RESPONSE TO MTX
M. Hara1, N. Ishiguro2, K. Katayama3, M. Kondo4, T. Sumida5, T. Mimori6, S. Soen7, K. Nagai8, T. Yamaguchi9, K. Yamamoto10, and Iguratimod Clinical Study Group. 1Institute of Rheumatology, Tokyo Women's Medical University, Tokyo; 2Department of Orthopaedic Surgery Nagoya University, Graduate School of Medicine& Faculty of Medicine, Nagoya; 3Katayama Orthopedic Rheumatology Clinic, Asahikawa; 4Kondo Clinic of Rheumatology and Orthopaedic Surgery, Fukuoka; 5Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba; 6Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto; 7Department of Orthopaedic Surgery and Rheumatology, Nara Hospital, Kinki University School of Medicine, Ikoma; 8Eisai Co., Ltd; 9Toyama Chemical Co., Ltd; 10Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Results: ACR20 response rate at Week 24 was 69.5% (114/164) in IM and 30.7% (27/88) in PM, demonstrating superiority of IM to PM. ACR50 and ACR70 response rates were 38.4% and 17.1% in IM, 15.9% and 5.7% in PM respectively; therefore, the response rates in IM were statistically higher than those in PM. Incidence of adverse events was 80.5% in IM and 75.0% in PM and the difference was not statistically significant. Serious adverse events were reported by 5 patients in IM and 3 patients in PM.Response rates of ACR20, ACR50 and ACR70 in IM at Week 52 were 71.3%, 49.4% and 23.8%, respectively.
Conclusions: Iguratimod in combination with MTX is promising to become an alternate effective treatment for RA patients with an inadequate response to MTX.


I think iguratimod is indeed a promising candidate for treatment of active rheumatoid arthritis and might become a needed alternative in the conventional (traditional) DMARD class.


23.07.2012
Here's the link: http://www.biospace.com/News/eisai-company-ltd-and-toyama-chemical-company/265468/source=TopBreaking