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Journal ArticleDOI

The emerging safety profile of JAK inhibitors in rheumatic disease

Kevin L. Winthrop
- 01 Apr 2017 - 
- Vol. 13, Iss: 4, pp 234-243
TLDR
Although nomalignancy signals have been identified to date, long-term follow-up and further research are needed to understand the risk of malignancy associated with these compounds, and vaccination is important to mitigate the risks of these emerging therapies.
Abstract
Tofacitinib is the first Janus kinase (JAK) inhibitor commercially approved for the treatment of rheumatoid arthritis. This compound and a number of other JAK inhibitors are currently being tested in phase II and III trials for the treatment of a variety of autoimmune inflammatory diseases. Whereas a characteristic safety profile is emerging for some JAK inhibitors, differences between individual agents might emerge on the basis of distinct potency against their molecular targets. Similarly to biological therapy, JAK inhibition can lead to serious and opportunistic infections, and viral infections seem to be particularly frequent. Although no malignancy signals have been identified to date, long-term follow-up and further research are needed to understand the risk of malignancy associated with these compounds. As is the case for biologic agents, vaccination is important to mitigate the risks of these emerging therapies.

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Citations
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NF-κB, inflammation, immunity and cancer: coming of age

TL;DR: How the initial discovery of a role for NF-κB in linking inflammation and cancer led to an improved understanding of tumour-elicited inflammation and its effects on anticancer immunity is discussed.
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Coronavirus disease 2019 (COVID-19) pandemic and pregnancy.

TL;DR: A review of COVID-19 in pregnancy, bringing together the various factors integral to the understanding of pathophysiology and susceptibility, diagnostic challenges with real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays, therapeutic controversies, intrauterine transmission and maternal-fetal complications.
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JAK inhibition as a therapeutic strategy for immune and inflammatory diseases.

TL;DR: The biology of JAKs is discussed from a translational perspective, focusing on recent insights from clinical trials, the development of novel agents and the use of jakinibs in a spectrum of immune and inflammatory diseases.
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The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells

TL;DR: This review represents how the JAK-STAT pathway is generally regulated and then in Th cell subsets in more detail and introduces novel targeted strategies as promising therapeutic approaches in the treatment of immune disorders.
Journal ArticleDOI

Interleukin-6: designing specific therapeutics for a complex cytokine

TL;DR: The roles of IL-6 in health and disease are overviewed and progress with several approaches of inhibitingIL-6-signalling is analyzed, with the aim of illuminating when and how to apply IL- 6 blockade.
References
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Journal ArticleDOI

Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins

TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
Journal ArticleDOI

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

TL;DR: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults and significantly reduced the burden of illness due to herpesZoster.
Journal ArticleDOI

JAKS AND STATS: Biological Implications*

TL;DR: The Jak-STAT pathway is the focus of this chapter, a novel mechanism in which cytosolic latent transcription factors, known as signal transducers and activators of transcription (STATs), are tyrosine phosphorylated by Janus family tyrosin kinases (Jaks), allowing STAT protein dimerization and nuclear translocation.
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