Background/Purpose: Iguratimod is a newly-developed disease-modifying antirheumatic drug (DMARD) that was approved in Japan in September 2012. It has been reported to suppress tumor necrosis factor-alpha-induced production of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein 1 via inhibition of nuclear factor kappa B activation in cultured human synovial cells and human acute monocytic leukemia cells. It can also reduce immunoglobulin production by acting directly on human B lymphocytes. A double-blind, placebo-controlled study of iguratimod in Japanese patients with rheumatoid arthritis (RA) revealed that it achieved a 20% improvement based on the American College of Rheumatology criteria (ACR20), being almost equivalent to the effect of salazosulfapyridine. In the present study, we examined the efficacy and safety of iguratimod as add-on therapy for patients with RA who had shown inadequate responses to previous therapy.

Methods: Patients with a diagnosis of RA according to the 2010 ACR/EULAR criteria who had been unresponsive to previous therapy, and who had been prescribed iguratimod as add-on therapy at Niigata Rheumatic Center between September 2012 and Feburary 2013 were enrolled. Details of the patients’ background factors, clinical parameters and laboratory findings, including C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), matrix metalloprotease-3 (MMP-3), rheumatoid factor (RF), Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]), Disease Activity Score for 28-joint counts based on the C-reactive protein (DAS28-4[CRP]), clinical disease activity index (CDAI) and simplified disease activity index (SDAI) were obtained from their medical records retrospectively. The efficacy of iguratimod was evaluated at week 12.

Results:  Twenty-six patients (5 males, 21 females) participated in this study. They had a mean age of 65.6 ±12.4 years and a mean disease duration of 7.5±8.3 years. Patients were treated with corticosteroids and/or DMARDs as monotherapy or in combination (corticosteroids 20 cases, salazosulfapyridine 18 cases, methotrexate 10 cases, bucillamine 5 cases, tacrolimus 5 cases, tocilizumab 1 case), together with iguratimod. Clinical parameters of disease activity at the baseline had improved 12 weeks later as follows: ESR, 29.9±25.9 mm/h to 25.8±21.5 mm/h (p = 0.33); CRP, 2.44±3.46 mg/dL to 1.27±1.64 mg/dL (p = 0.11); MMP-3, 257.7±160.0 ng/mL to 207.5±128.0 ng/mL (p = 0.17); RF, 141.3±168.7 U/mL to 97.6±121.0 IU/mL (p = 0.011); DAS28-4[ESR], 4.36 ± 3.46 to 3.75 ± 1.00 (p=0.053); DAS28-4[CRP], 3.96±1.28 to 3.27±0.94 (p= 0.02); SDAI, 18.9±13.6 to 13.3±6.2 (p= 0.062); CDAI, 17.0±10.6 to 12.0±5.5 (p= 0.042). Among these 26 patients, 5 discontinued taking iguratimod because of nausea in 2, skin rash in 1, brain hemorrhage in 1, and pulmonary hemorrhage in 1 who was receiving warfarin.

Conclusion: Iguratimod is effective as add-on therapy in RA patients who have shown inadequate responses to previous therapy, although caution is necessary regarding hemorrhagic tendency in patients receiving warfarin, which was cautioned by Ministry of Health, Labour and Welfare of Japan.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-a-novel-disease-modifying-antirheumatic-drug-iguratimod-as-add-on-therapy-for-patients-with-rheumatoid-arthritis/