Browsing by Subject "Rheumatoid Arthritis"

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    Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial
    (BMJ Publishing Group, 2016-06) Takeuchi, Tsutomu; Tanaka, Yoshiya; Ishiguro, Naoki; Yamanaka, Hisashi; Yoneda, Toshiyuki; Ohira, Takeshi; Okubo, Naoki; Genant, Harry K.; van der Heijde, Désirée; Department of Medicine, IU School of Medicine
    OBJECTIVES: To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA). METHODS: In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months. RESULTS: Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo. CONCLUSIONS: Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. TRIAL REGISTRATION NUMBER: JapicCTI-101263.
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    Expression and Activities of Matrix Metalloproteinases under Oscillatory Shear in IL-1-Stimulated Synovial Cells
    (2003) Sun, Hui Bin; Nalim, M. Razi; Yokota, Hiroki
    Matrix metalloproteinases (MMPs) are known to play a critical role in tissue disintegration, and an elevated level of MMPs is observed in synovium and synovial fluid of joints with rheumatoid arthritis. During joint movement, synovial tissue receives various mechanical stimuli, but effects of mechanical challenges on regulation of MMPs in rheumatic synovium are poorly understood. Focusing on cellular responses to oscillatory fluid shear in human synovial cells, we determined the expression of MMP-1 and MMP-13 by polymerase chain reaction and immunoblotting as well as proteolytic activities of total MMPs by a fibril degradation assay and zymography. The results revealed that ~0.5 dyn/cm 2 oscillatory shear at 1 Hz not only reduced an mRNA level and a protein level of MMP-1 and MMP-13, but it also decreased collagenase and gelatinase activities of total MMPs. Furthermore, the induction of the MMP expression and activities by interleukin-1 was suppressed by the oscillatory shear. Interestingly, the oscillatory shear upregulated the mRNA expression of TIMP-1 and TIMP-2. Our results support a potential role of oscillatory shear in regulating expression and activities of MMPs in the presence and the absence of proinflammatory cytokine.
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    Gene expression signatures of target tissues in type 1 diabetes, lupus erythematosus, multiple sclerosis, and rheumatoid arthritis
    (American Association for the Advancement of Science, 2021-01-06) Szymczak, F.; Colli, M.L.; Mamula, M.J.; Evans-Molina, C.; Eizirik, D.L.; Medicine, School of Medicine
    Autoimmune diseases are typically studied with a focus on the immune system, and less attention is paid to responses of target tissues exposed to the immune assault. We presently evaluated, based on available RNA sequencing data, whether inflammation induces similar molecular signatures at the target tissues in type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. We identified confluent signatures, many related to interferon signaling, indicating pathways that may be targeted for therapy, and observed a high (>80%) expression of candidate genes for the different diseases at the target tissue level. These observations suggest that future research on autoimmune diseases should focus on both the immune system and the target tissues, and on their dialog. Discovering similar disease-specific signatures may allow the identification of key pathways that could be targeted for therapy, including the repurposing of drugs already in clinical use for other diseases.
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    Pre- and post-conception planning in autoimmune disorders
    (2020-03) Kumar, Nimisha; Aksu, Eric; Gensel, Annie; Burger, Taylor; Pease, Kensey
    Background: Autoimmune diseases are often multisystem, requiring many specialists. However, there are no clear recommendations for many of these disorders for planning pregnancy and preventing exacerbations. Intervention: Little time is devoted to patient counseling about contraception or care antepartum, intrapartum, and postpartum. Contraception and many first-line interventions can have varying effects in different diseases, which can be further complicated by multiple diagnoses. Many of these disorders also can have postpartum complications, making follow-up essential. Results:Systemic lupus erythematosus (SLE) is known to cause exacerbations during pregnancy and has serious adverse outcomes for both mother and baby. Active disease is associated with higher rates of preterm birth, pre-eclampsia, thromboses, fetal loss, and neonatal lupus. Patients are at increased risk of these complications with a history of lupus nephritis, cessation of hydroxychloroquine, and primigravidity. Multiple sclerosis (MS) has lower rates of relapse during pregnancy, but higher rates in the first postpartum year. This has been attributed to the rapid increase in progesterone during pregnancy improving symptoms, while the rapid decrease after pregnancy promotes relapses. Additionally, neonatal morbidity does not increase as a result of MS. For other autoimmune diseases such as Sjögren's Syndrome or Grave’s Disease, the clinical picture may be complicated by the physiology of pregnancy, but is unclear whether pregnancy exacerbates the autoimmune component of the disease. Conclusions: Pregnancy and contraception could improve or worsen symptoms in autoimmune diseases, even up to a year postpartum. There is a significant gap in practice guidelines regarding contraception and pregnancy despite many diseases’ onset during childbearing years. Pregnancy and contraception counseling should be part of initial conversations at diagnosis to prepare women.