Safety and efficacy of T-614 in the treatment of patients with active rheumatoid arthritis: a double blind, randomized, placebo-controlled and multicenter trial

Lu, Liangjing; Teng, Jialin; Bao, Chunde; Han, Xiaoxu; Sun, Lingyun; Xu, Jiang-hua; LI, Xing-fu; Wu, Huaxiang

doi:10.1097/00029330-200804010-00008

Cited by 28 publications

(51 citation statements)

References 8 publications

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“…In previous clinical trials conducted by our group on RA, iguratimod showed no severe side-effects in RA patients at 50 mg/d. [3] , [4] , [24] The most common manifestations were reversible elevated liver enzymes and decreased peripheral white blood cell counts [4] , [24] . Hence, we monitored serum alanine transaminase (ALT) and complete blood cell counts (CBC) of MRL/lpr mice at 15, 19 and 27 weeks of age during iguratimod treatment.…”

Section: Resultsmentioning

confidence: 99%

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Prevention of Immune Nephritis by the Small Molecular Weight Immunomodulator Iguratimod in MRL/lpr Mice

Yan

Huang

et al. 2014

PLoS ONE

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ObjectiveThis study was performed to investigate the therapeutic effects of iguratimod in a lupus mouse model.MethodsFemale MRL/lpr mice were treated with iguratimod, vehicle solution or cyclophosphamide. Proteinuria was monitored and kidney injury was blindly scored by a renal pathologist. Serum anti-double-stranded DNA antibodies were monitored by radioimmunoassay. Kidney IgG and CD20 were stained by immunohistochemistry. Splenic lymphocyte phenotypes were analyzed by flow cytometry. BAFF, IL-17A, IL-6, and IL-21 levels in serum and splenic lymphocytes were detected by ELISA or quantitative PCR.ResultsCompared with the vehicle-treated controls, MRL/lpr mice treated with iguratimod showed less protenuria, less acute pathological lesions and no chronic changes in the kidneys. There were significant differences in glomerular injury and vasculitis scores, as well as in the semi-quantitave analysis of immune complex deposition between the two groups. Disease activity markers in sera (anti-dsDNA antibodies and immunoglobulin levels) were reduced and hypocomplementemia was attenuated. Lymphocyte expression of BAFF, IL-6, IL-17A and IL-21 was decreased. The abnormal splenic B220+ T cell and plasma cell populations in MRL/lpr mice were reduced by iguratimod treatment, with recovery of the total B cell population and inhibition of B cell infiltration of the kidney tissue. The dosage of iguratimod used in this study showed no significant cytotoxic effects in vivo and no overt side-effects were observed.ConclusionIguratimod ameliorates immune nephritis in MRL/lpr mice via a non-antiproliferative mechanism. Our data suggest a potential therapeutic role of iguratimod in lupus.

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Section: Resultsmentioning

confidence: 99%

“…We, and other researchers, have demonstrated the therapeutic effect of iguratimod both in the collagen-induced arthritis (CIA) model [1] , [2] and in clinical trials for rheumatoid arthritis (RA). [3] – [5] This agent has been approved for treating RA in several countries over the last 3 years.…”

Section: Introductionmentioning

confidence: 99%

Prevention of Immune Nephritis by the Small Molecular Weight Immunomodulator Iguratimod in MRL/lpr Mice

Yan

Huang

et al. 2014

PLoS ONE

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“…The synovial milieu is characterized by an elevated level of T lymphocytes, TNF-α, and other inflammatory factors that result in bone, cartilage, and tendon destruction. 44,64 The major problem with RA is its chronic nature, which over time (~15 years) leads to severe disability (1.7 million patients in higher income countries and 3.7 million patients in lower income countries) in the population >60 years old. 65 Moreover, 68% of patients suffer from severe pain, especially in the morning, due to joint stiffness.…”

Section: Introductionmentioning

confidence: 99%

Iguratimod: a valuable remedy from the Asia Pacific region for ameliorating autoimmune diseases and protecting bone physiology

Bao²,

Zeng³

et al. 2019

Bone Res

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Autoimmune diseases are affected by complex pathophysiology involving several cell types, cytokines, antibodies, and mimicking factors. Different drugs are used to ameliorate these autoimmune reactions, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antiantibodies, and small molecular drugs (DMARDs), and they are clinically in vogue for diseases such as rheumatoid arthritis (RA). Nevertheless, low cost-effectiveness, reduced efficacy, adverse effects, and patient nonresponse are unappealing factors driving the development of new drugs such as iguratimod. Iguratimod is primarily used to ameliorate RA in Japanese and Chinese clinics. However, its efficacy against other autoimmune ailments is also under intense investigation, and the number of investigations is becoming increasingly larger with each passing day. The articular structure comprises synovium, ligaments, and bone. The latter is more complex than the others since it regulates blood cells and autoimmunity in addition to providing skeletal support to the body. Therefore, its protection is also of prime importance in RA and other autoimmune diseases. Herein, we have highlighted the role of iguratimod in autoimmune diseases and bone protection. We suggest that iguratimod's unique mode of action compared with that of other DMARDs and its good patient response makes it a suitable antirheumatic and bone-protecting drug.Bone Research (2019) 7:27 ; https://doi.Fig. 2 Effects of iguratimod and other DMARDs on collagen-induced arthritis. a Arthritis score in different DMARD-treated groups. b Arthritis incidence of different treated groups. c The extent of paw edema in various groups. d The body weight measured in various groups after DMARD treatment. e X-ray radiographs of various groups treated with different DMARDs. Arrows indicate the bone erosion area, whereas * and ** indicate significance P-values of <0.05 and 0.01 (*P < 0.05, **P < 0.01), respectively. Adapted from Ref. 21

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“…Rheumatoid arthritis (RA) is a chronic systemic inflammatory and autoimmune disease which is relatively common with a prevalence of slightly <1% in adults all over the world and can result in erosion and destruction of cartilage, bone and tendon (Li et al, 2013;Lü et al, 2008;Luo et al, 2013). As a result, RA leads to a consequent reduction in the quality of life.…”

Section: Introductionmentioning

confidence: 99%

A rapid and sensitive LC–MS/MS method for analysis of iguratimod in human plasma: Application to a pharmacokinetic study in Chinese healthy volunteers

Xia

Zhao²,

Gong

et al. 2018

Biomedical Chromatography

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A rapid, sensitive and reproducible LC-MS/MS method was developed and validated to determine iguratimod in human plasma. Sample preparation was achieved by protein precipitation with acetonitrile. Chromatographic separation was operated on an Ultimate® XB-C column (2.1 × 50 mm, 3.5 μm, Welch) with a flow rate of 0.400 mL/min, using a gradient elution with acetonitrile and water which contained 2 mm ammonium acetate and 0.1% formic acid as the mobile phase. The detection was performed on a Triple Quad™ 5500 mass spectrometer coupled with an electrospray ionization interface under positive-ion multiple reaction monitoring mode with the transition ion pairs of m/z 375.2 → 347.1 for iguratimod and m/z 244.3 → 185.0 for agomelatine (the internal standard), respectively. The method was linear over the range of 5.00-1500 ng/mL with correlation coefficients ≥0.9978. The accuracy and precision of intra- and inter-day, dilution accuracy, recovery and stability of the method were all within the acceptable limits and no matrix effect or carryover was observed. As a result, the main pharmacokinetic parameters of iguratimod were as follows: C , 1074 ± 373 ng/mL; AUC , 13591 ± 4557 ng h/mL; AUC , 13,712 ± 4613 ng h/mL; T , 3.29 ± 1.23 h; and t , 8.89 ± 1.23 h.

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Safety and efficacy of T-614 in the treatment of patients with active rheumatoid arthritis: a double blind, randomized, placebo-controlled and multicenter trial

Cited by 28 publications

References 8 publications

Prevention of Immune Nephritis by the Small Molecular Weight Immunomodulator Iguratimod in MRL/lpr Mice

Prevention of Immune Nephritis by the Small Molecular Weight Immunomodulator Iguratimod in MRL/lpr Mice

Iguratimod: a valuable remedy from the Asia Pacific region for ameliorating autoimmune diseases and protecting bone physiology

A rapid and sensitive LC–MS/MS method for analysis of iguratimod in human plasma: Application to a pharmacokinetic study in Chinese healthy volunteers

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