Tuesday, December 9, 2014

Iguratimod at the ACR 2014 in Boston

I have already been interested in iguratimod (IGU) for a while. I’ve blogged on IGU for the first time 2 ½ years ago after the EULAR meeting in Berlin (2012). I had been a bit disappointed in 2013, when there had been only a Chinese cell study (Iguratimod inhibits RANKL-induced osteoclastogenesis in RAW264.7 cells) at the 2013 EULAR meeting in Madrid. Earlier this year at the EULAR meeting in Paris IGU returned with three posters/studies. Please see below. Iguratimod already has been approved for the Japanese market (2012); see below. It is marketed under the brand names Careram® and KOLBET®.

Y. Kanayama and colleagues presented the following study [#1488]: “Clinical Efficacy of Add-on Iguratimod Therapy in Patients with Active Rheumatoid Arthritis Despite of Methotrexate - a Multicenter Registry.” It#s hard to tell, what this study is. I think, the authors aggregated data from existing studies and looked at 51 patients, who fulfilled the ACR/EULAR criteria for RA and didn’t respond to MTX. DAS had been reduced from 4.67 to 3.32 after 24 weeks, CDAI from 16.9 to 7.9. Remission rates were 33.3% for DAS and 27.5% for CDAI. Conclusion: “This study suggested that the new combination therapy of add-on IGU with MTX was effective in patients with active RA with inadequate response to MTX.”

Y. Hirano and colleagues presented another study [#1489]: “Influences of Disease Activity at the Initiation of Iguratimod, a Small Molecule Antirheumatic Drug, on Efficacy of Iguratimod in Patients with Rheumatoid Arthritis –a Multicenter Registry Study”. They looked at 79 patients. The study period also had been 24 weeks. In results we find: “The mean DAS28-CRP at 0, 4, 8, 12 and 24w was 4.99, 4.49, 4.29, 3.70 and 3.58 in HG [high disease activity group] and 3.24, 3.16, 2.76, 2.62 and 2.56 in MLG [moderate and low disease activity group]. DAS28-CRP was significantly decreased after 4w in HG and after 8w in MLG.” Conclusion: “This study suggests that IGU is one of the options not only in RA patients with high disease activity treated with insufficient MTX.”

T. Kondo and colleagues presented a third study [#1497]: “Efficacy and Safety of Iguratimod for Rheumatoid Arthritis.” They looked at 62 patients, who received 25 mg iguratimod during the first month and who were changed to a dosage of 50 mg afterwards. “DAS28-ESR and SDAI decreased significantly from 4.49_1.33 to 3.09_1.12 and from 18.5_10.9 to 7.44_7.11 in 24 weeks respectively (P_0.01).” “Adverse events were digestive symptom (n=6), liver dysfunction (n=3), nasal hemorrhage (n=2) and so on. There’s no severe adverse event.”  Conclusion: Iguratimod was well tolerable and may have a good cost effectiveness. So iguratimod be a new useful option as small molecule DMARDs for RA patients in a manner similar to tofacitinib.”

Sorry, as much as I want a new DMARD to treat patients with RA, who can’t receive biologics, these studies aren’t convincing and won’t be sufficient to get an approval by FDA or EMEA for iguratimod. The studies didn’t define primary endpoints, consisted of aggregated data, weren’t blinded or placebo controlled. Kondo’s conclusions are far fetched: “may have a good cost effectiveness” (cost effectiveness hadn’t been tested), “similar to tofacitinib” (hadn’t been tested against tofacitinib). And were is data on radiographic progression? As tofacitinib has been mentioned – radiographic progression was one of the critical points for not having yet optained approval by EMEA.

I’m still in favour of iguratimod, but the company has to sponsor better powered and designed studies. These studies have to include data on radiographic progression.


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