Friday, June 23, 2017

Iguratimod at the 2017 EULAR Annual Meeting in Madrid



I’ve been following the development of iguratimod very closely since 2012 [1]. Iguratimod is a disease modifying anti-rheumatic drug (DMARD); chemical formula: N-(3-Formamido-4-oxo-6-phenoxy-4H-chromen-7-yl)-methanesulfonamide. “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.” It is approved for the treatment of rheumatoid arthritis in Japan as well as in China![2]

There had been four abstracts on iguratimod at the 2017 EULAR Annual Meeting in Madrid.

K. Tokunaga and colleagues looked at [3]: “COMPARISON OF EFFICACY BETWEEN COMBINATION THERAPY WITH IGURATIMOD [IGU] AND SULFASALAZINE [SSZ] WITH METHOTREXATE IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS: PROPENSITY SCORE ANALYSIS”. Luckily the study excluded DMARDs like tacrolimus and bucillamine, which aren’t approved worldwide for rheumatoid arthritis. In results we read: “The remission rates of DAS28-CRP in the following year was 77.2% (44/57 patients) and 71.7% (38/53 patients; P=0.52) in the IGU and SSZ groups, respectively.” Conclusions: “Combination therapy with IGU or SSZ and methotrexate for rheumatoid arthritis did not show a significant difference in disease activity. Further studies are needed.“ According to this study iguratimod fits into the group of csDMARDs like methotrexate, leflunomide, sulfasalazine, azathioprine.

Y. Hirano and colleagues presented [4]: “LONG-TERM OUTCOME OF IGURATIMOD, CONVENTIONAL SYNTHETIC DISEASE-MODIFYNG ANTI-RHEUMATIC DRUD DEVELOPED IN JAPAN, IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL-WORLD CLINICAL SETTING”. “82% of patients had factors influencing to prescribing IGU and intolerance of dose escalation of MTX was 1st reason (23.3%), old age over 80 years old was 2nd reason (16.7%) and economical reason was 3rd (14.2%)”. In conclusions the authors hinted t: “Although biological DMARDs is effective in RA patients, the cost is very expensive. IGU is comparative cheap (¥9,200/month) and suitable for RA patients with economical difficulties.” ¥9,200 is a little less than 75 €.

T. Suto and colleagues also presented long term data [5]: “EFFICACY AT THREE YEARS OF DAILY CLINICAL USE OF IGURATIMOD IN PATIENTS WITH RHEUMATOID ARTHRITIS”. “The survival rate at 3 years was 49.3%, and 8 patients discontinued the IGU therapies due to insufficient response, 12 patients due to adverse events such as exanthema, pneumonitis or hepatic disorder, and other patients based on their requests.” Conclusions: “We assessed middle-term outcome of the clinical use of iguratimod therapy in RA patients. The low DAS28-CRP and low usage rate of prednisolone at the initiation of IGU were significant factors of clinical remission achievement at 3 years.”

Iguratimod could be a useful addition to existing csDMARDs, but would have to be evaluated in randomized controlled studies. Maybe a pharmaceutical firm in Europe or the US should buy the patent for the non-Asian market and evaluate iguratimod in studies that are needed to get EMA or FDA approval. Otherwise only Japanese and Chinese patients will have access to iguratimod.


Links and References:
[3] DOI: 10.1136/annrheumdis-2017-eular.6157
[4] DOI: 10.1136/annrheumdis-2017-eular.4852
[5] DOI: 10.1136/annrheumdis-2017-eular.6040

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