Background/Purpose

 Iguratimod (IGU) is a small-molecule antirheumatic drug that was approved in Japan in September 2012. IGU suppressed tumor necrosis factor-alpha-induced production of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein 1 via inhibition of nuclear factorkappa B activation in cultured human synovial cells and human acute monocytic leukemia cells. IGU also reduced immunoglobulin production by acting directly on human B lymphocytes without affecting B lymphocyte proliferation. Recently, an increased release of extracellular adenosine and a decreased production of lymphotoxins such as ammonia and superoxide have been shown to be involved in the anti-inflammatory mechanisms of methotrexate. Thus, the combination of MTX and IGU may have synergic efficacy for rheumatoid arthritis (RA) treatment. To evaluate the clinical efficacy of add-on IGU in patients with Japanese active RA who had shown inadequate responses to MTX therapy.

Methods

Patients with a diagnosis of RA according to the 2010 ACR/EULAR criteria who had been unresponsive to MTX therapy (DAS>3.2 or CDAI>10), and who had been prescribed add-on IGU from Tsurumai Biologics Communication Registry (TBCR) between November 2012 and August 2013 were enrolled. The final study cohort of 51 patients received continuous IGU therapy more than 24 weeks. We reviewed the methods about the improvement of CRP, MMP3, DAS28-ESR and CDAI which was an index of disease activity of RA using Wilcoxon signed-rank test and the rate of remission patients at Week24.

Results

The group of patients included 8 males and 43 females. The mean age was 63.6 ± 10.3 years old; the disease duration was 8.4 ± 9.7 years and the methotrexate dose was 9.6 ± 4.2 mg/week. Clinical findings related to RA were as follows: mean tender joint count, 4.5 ± 4.9; swollen joint count, 4.2 ± 3.9; patient’s global assessment of disease activity, 41.5 ± 22.8mm; Physician’s global assessment of disease activity, 40.0 ± 20.8mm; CRP, 2.0 ± 2.3 mg/dL; ESR, 42.9 ± 19.2 mm/h; MMP3, 249.7 ± 284.6 ng/ml; DAS28 (ESR), 4.67 ± 0.97; and CDAI, 16.9 ± 9.4. There were no patients who had received Biologics treatment. The mean CRP improved to 1.7 ± 2.2, 1.2 ± 2.0 and 1.1± 1.9 at Week 4, 12 and 24 (p=0.064, p<0.001, p<0.001), mean MMP3 improved to 223.7 ± 266.1, 161.7 ± 242.1 and 148.3 ± 244.4 at Week 4, 12 and 24 (p=0.045, p<0.001, p<0.001), the mean DAS28 improved to 4.26 ± 1.03, 3.44 ± 1.07 and 3.32± 1.28 at Week 4, 12 and 24 (p<0.001, p<0.001, p < 0.001) and the mean CDAI improved to 13.1 ± 8.2, 8.3 ± 6.5 and 7.9± 7.6 at Week 4, 12 and 24 (p<0.001, p<0.001, p < 0.001) significantly. At Week 24 the rate of patients who achieved remission were each 33.3% and 27.5% in DAS and CDAI criteria.

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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-efficacy-of-add-on-iguratimod-therapy-in-patients-with-active-rheumatoid-arthritis-despite-of-methotrexate-a-multicenter-registry-study/