A Mechanism of Action for Cyclosporine a in Ulcerative Colitis: The Role of the Tec Kinase Itk in Disease Pathogenesis

Weigmann, Benno; Mott, Stefanie; Atreya, Raja

doi:10.1016/s0016-5085(17)32632-x

Cited by 3 publications

(2 citation statements)

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“…Ritlecitinib (PF-06651600) is a dual irreversible inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family. The addition of a TEC inhibitor widens the anti-inflammatory potential and some TEC family members are considered as a treatment target in inflammatory diseases [ 46 ].…”

Section: Selective Jak Inhibitorsmentioning

confidence: 99%

Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment

Dudek

Fabisiak

Zatorski

et al. 2021

JCM

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Although development of biologics has importantly improved the effectiveness in inducing and maintaining remission in inflammatory bowel disease (IBD), biologic therapies still have several limitations. Effective, low-cost drug therapy with good safety profile and compliance is therefore a substantial unmet medical need. A promising target for IBD treatment strategies are Janus kinase (JAK) inhibitors, which are small molecules that interact with cytokines implicated in pathogenesis of IBD. In contrast to monoclonal antibodies, which are able to block a single cytokine, JAK inhibitors have the potential to affect multiple cytokine-dependent immune pathways, which may improve the therapeutic response in some IBD patients. Tofacitinib, inhibiting signaling via different types of JAKs, has been already approved for ulcerative colitis, and several other small-molecule are still under investigation. However, one of the main concerns about using JAK inhibitors is the risk of thromboembolic events. Moreover, patients with COVID-19 appear to have an increased susceptibility for immunothrombosis. Therefore, thrombotic complications may become a serious limitation in the use of JAK inhibitors in the SARS-CoV-2 pandemic. As many questions about safety and efficacy of small molecules still remain unclear, in our review we present the current data regarding approved JAK inhibitors, as well as those in clinical development for the treatment of IBD.

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Section: Selective Jak Inhibitorsmentioning

confidence: 99%

Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment

Dudek

Fabisiak

Zatorski

et al. 2021

JCM

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“…Furthermore, B-cell responses, which are dependent on T-cell, are also restrained, and as a result, both humoral and cell-mediated immune responses are quelled. This immunosuppressive superiority of CsA has revolutionized transplant medicine(Weigmann, Mott, Atreya, & Neurath, 2017). According to the US Food and Drug Administration (FDA) CsA is classified as class C drug for pregnancy.…”

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confidence: 99%

Cyclosporine A improves pregnancy outcomes in women with recurrent pregnancy loss and elevated Th1/Th2 ratio

Azizi

Ahmadi

Danaii

et al. 2019

Journal Cellular Physiology

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Recurrent pregnancy loss (RPL) is a one of the most common obstetrical complications. Since, the successful pregnancy occurs in T helper 2 (Th2)‐dominant situation and since, Th1 type immunity is related to pregnancy failure, we investigated the effects of cyclosporine on Th1 and Th2 cells in RPL women. Totally, 76 RPL patients (38 women as treated group and 38 as control group) were included in this study. Flow cytometry was utilized to analyze the frequency of Th1 and Th2 in blood samples. Also, real‐time polymerase chain reaction was carried out to assess the messenger RNA (mRNA) expression of transcription factors and enzyme‐linked immunosorbent assay was used to evaluate Th1 and Th2 related cytokines. Significant decrease in Th1 frequency (p = 0.0004), Th1/Th2 ratio (p < 0.0001), T‐bet mRNA expression (p < 0.0001), interferon‐γ (p = 0.0007), and tumor necrosis factor α (p = 0.0002) secretion level were observed in cyclosporine group. Moreover, significant increase in Th2 frequency (p < 0.0001), mRNA expression of GATA binding protein 3 (p = 0.0001), and interleukin 10 secretion level (p = 0.0027) was also evident in treated group. At the end of the investigation, 31 (81.5%) patients in cyclosporine‐treated group had successful childbirth when compared with 16 (42.1%) women in control group (p = 0.0001). Given this, cyclosporine treatment for RPL patients with elevated Th1/Th2 ratio can result in improved pregnancy outcome.

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Osteopathic Primary Care Treatment Options for Ulcerative Colitis

Fernandez

Januchowski

2020

OFP

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Introduction: Ulcerative colitis is a multifactorial, chronic inflammatory disease of the bowel that can cause physical, social and emotional injury to the patient. While perhaps not always making the initial diagnosis or providing primary treatment, the primary care physician can play a critical role in providing direction and clarity to the overall treatment plan for the patient. In addition, monitoring for complications or side effects of treatment will help maintain the patient’s optimal health. Methods: A literature search using PubMed, NCBI and WorldCat.org was done using the terms ulcerative colitis treatment, psychosocial association of ulcerative colitis, surgical management of ulcerative colitis, epidemiology of ulcerative colitis, the pathophysiology of ulcerative colitis, probiotics in ulcerative colitis, OMT for ulcerative colitis, and diagnosis of ulcerative colitis. A primary date range of 2015-2019 was used with a secondary search extending back to 1985. Discussion: An Osteopathic approach to the treatment of ulcerative colitis will help the patient remain highly functioning and reduce complications of this disease. By being aware of the various pharmaceutical and non-pharmaceutical treatment options available, one can collaborate with the patient to create a treatment plan to minimize morbidity and increase functional days.

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A Mechanism of Action for Cyclosporine a in Ulcerative Colitis: The Role of the Tec Kinase Itk in Disease Pathogenesis

Cited by 3 publications

References 0 publications

Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment

Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment

Cyclosporine A improves pregnancy outcomes in women with recurrent pregnancy loss and elevated Th1/Th2 ratio

Osteopathic Primary Care Treatment Options for Ulcerative Colitis

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