Journal ArticleDOI
The emerging safety profile of JAK inhibitors in rheumatic disease
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.read more
Citations
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NF-κB, inflammation, immunity and cancer: coming of age
Koji Taniguchi,Michael Karin +1 more
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.
Journal ArticleDOI
Coronavirus disease 2019 (COVID-19) pandemic and pregnancy.
Pradip Dashraath,Jing Lin Jeslyn Wong,Mei Xian Karen Lim,Li Min Lim,Sarah Li,Arijit Biswas,Mahesh Choolani,Citra Nurfarah Zaini Mattar,Lin Lin Su +8 more
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.
Journal ArticleDOI
JAK inhibition as a therapeutic strategy for immune and inflammatory diseases.
Daniella M. Schwartz,Yuka Kanno,Alejandro V. Villarino,Michael E. Ward,Massimo Gadina,John J. O'Shea +5 more
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.
Journal ArticleDOI
The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells
Farhad Seif,Majid Khoshmirsafa,Hossein Aazami,Monireh Mohsenzadegan,Gholam Reza Sedighi,Mohammad Ali Bahar +5 more
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
2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis
Jasvinder A. Singh,Kenneth G. Saag,S. Louis Bridges,Elie A. Akl,Raveendhara R. Bannuru,Matthew C. Sullivan,Elizaveta E. Vaysbrot,Christine McNaughton,Mikala C. Osani,Robert H. Shmerling,Jeffrey R. Curtis,Daniel E. Furst,Deborah Parks,Arthur Kavanaugh,James R. O'Dell,Charles H. King,Amye Leong,Eric L. Matteson,John T. Schousboe,Barbara E. Drevlow,Seth Ginsberg,James Grober,E. William St. Clair,Elizabeth A. Tindall,Amy S. Miller,Timothy E. McAlindon +25 more
TL;DR: To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA), a large number of patients with RA are referred to a single clinic for treatment with these medications.
Journal ArticleDOI
A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.
Michael N. Oxman,Michael N. Oxman,Myron J. Levin,Gary R. Johnson,Kenneth E. Schmader,Sharon E. Straus,Lawrence D. Gelb,Robert D. Arbeit,Michael S. Simberkoff,Anne A. Gershon,Larry E. Davis,Adriana Weinberg,Kathy D. Boardman,Heather M. Williams,J. Hongyuan Zhang,Peter Peduzzi,C. E. Beisel,Vicki A. Morrison,John C. Guatelli,P. A. Brooks,C. A. Kauffman,Constance T. Pachucki,Kathleen M. Neuzil,Robert F. Betts,Peter F. Wright,Marie R. Griffin,P. Brunell,N. E. Soto,Adriana Marques,Susan Keay,R. P. Goodman,D. J. Cotton,John W. Gnann,J. Loutit,Mark Holodniy,Wendy A. Keitel,George E. Crawford,S. S. Yeh,Z. Lobo,John F. Toney,Richard N. Greenberg,Paul M. Keller,Ruth Harbecke,Anthony R. Hayward,Michael R. Irwin,Tassos C. Kyriakides,Christina Y. Chan,Ivan S. F. Chan,William Wang,Paula W. Annunziato,Jeffrey L. Silber +50 more
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*
Warren J. Leonard,John J. O'Shea +1 more
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.
Journal ArticleDOI
2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host
Lorry G. Rubin,Myron J. Levin,Per Ljungman,E. Graham Davies,Robin K. Avery,Marcie Tomblyn,Athos Bousvaros,Shireesha Dhanireddy,Lillian Sung,Harry L. Keyserling,Insoo Kang +10 more
TL;DR: An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children intended for use by primary care and subspecialty providers who care for immuno-compromised patients.
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