JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis

Rheumatology
George E FragoulisStefan Siebert

Abstract

Janus kinase (JAK)/signal transducers and activators of transcription (STATs) are a group of molecules associated with one of the major pathways through which many cytokines exert and integrate their function, and as such they are increasingly recognized as playing critical role in the pathogenesis subserving various immune-mediated diseases, including RA, PsA, SpAs, IBD, skin disorders (e.g. alopecia areata, atopic dermatitis), single-gene disorders like interferonopathies, and others. JAKs are the key initiating players of the JAK/STAT pathway. Upon binding of their respective effector molecules (cytokines, IFNs, growth factors and others) to type I and type II receptors, JAKs are activated, and through phosphorylation of themselves and of other molecules (including STATs), they mediate signal transduction to the nucleus. A class of drugs-called JAK inhibitors or JAKinibs-that block one or more JAKs has been developed in the last decade, and now numbers >20 members. Although, so far, JAK inhibitors have been marketed only for RA and PsA, these drugs have been tested in phase 2 and phase 3 clinical trials for other inflammatory conditions and beyond. In this review, we summarize the clinical data, including efficacy and safety...Continue Reading

References

Jan 19, 2006·The Journal of Investigative Dermatology·Deepak RajDouglas Grossman
Jul 4, 2009·Nature Reviews. Immunology·Sarah L Gaffen
Jul 16, 2010·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Chao ChenYan Wang
Nov 12, 2010·Annals of the Rheumatic Diseases·Stuart I DavidsonHuji Xu
Jan 28, 2012·Journal of the American Academy of Dermatology·Naresh PunwaniAlice Gottlieb
Aug 17, 2012·The New England Journal of Medicine·William J SandbornUNKNOWN Study A3921063 Investigators
Apr 3, 2013·Annals of the Rheumatic Diseases·John J O'SheaArian Laurence
Oct 18, 2013·Experimental Dermatology·Kamran Ghoreschi, Massimo Gadina
Dec 24, 2013·Nature Reviews. Immunology·Lionel B Ivashkiv, Laura T Donlin
Feb 1, 2014·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·William J SandbornUNKNOWN Study A3921043 Investigators
Jul 17, 2014·The New England Journal of Medicine·Y LiuR Goldbach-Mansky
Dec 30, 2014·The New England Journal of Medicine·Thorsten HornungJoerg Wenzel
Jun 25, 2015·JAMA Dermatology·Brittany G Craiglow, Brett A King
Jul 1, 2015·The British Journal of Dermatology·N PunwaniA B Gottlieb
Jul 8, 2015·The British Journal of Dermatology·K A PappUNKNOWN OPT Pivotal 1 and OPT Pivotal 2 investigators
Jul 22, 2015·Journal of the American Academy of Dermatology·Lauren L LevyBrett A King
Oct 20, 2015·Arthritis & Rheumatology·Massimo GadinaJohn J O'Shea
Nov 3, 2015·The Journal of Rheumatology. Supplement·Ugo FioccoLeonardo Punzi
Dec 10, 2015·JAMA Dermatology·Brittany G CraiglowBrett A King
Dec 22, 2015·Journal of the American Academy of Dermatology·John E HarrisJulian Mackay-Wiggan
Feb 27, 2016·The Journal of Investigative Dermatology·Joerg WenzelDominik Wolf
Mar 31, 2016·The New England Journal of Medicine·Mark C GenoveseJosef S Smolen
Oct 21, 2016·Journal of the European Academy of Dermatology and Venereology : JEADV·F ValenzuelaC Mamolo
Jun 15, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Craig ZetterbergNiresh Hariparsad
Oct 30, 2016·The British Journal of Dermatology·R BissonnetteW C Ports

❮ Previous
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Citations

Jun 6, 2019·Nature Reviews. Rheumatology·Grainne Murphy, David A Isenberg
Sep 6, 2019·Expert Review of Clinical Immunology·Melinda J GooderhamMark G Lebwohl
Dec 18, 2019·Annals of the Rheumatic Diseases·Josef S Smolen
Mar 21, 2020·Expert Opinion on Emerging Drugs·Esther A BaloghSteven R Feldman
Nov 20, 2019·Allergy, Asthma & Immunology Research·Ioana AgacheLiliana Rogozea
Jul 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Adriana CoricelloStefano Alcaro
Aug 19, 2020·Chinese Medical Journal·Yong FanZhuo-Li Zhang
May 29, 2020·Annals of the Rheumatic Diseases·Jinjing LiuWenjie Zheng
Sep 6, 2020·Current Opinion in Rheumatology·Sofia Serena Tsakali, Catherine M Shanahan
Jun 4, 2019·International Reviews of Immunology·Shachi Pranjal VyasRitobrata Goswami
Feb 20, 2020·Journal of Cellular Physiology·Arezoo HosseiniBehzad Baradaran
Jul 3, 2020·Therapeutic Advances in Musculoskeletal Disease·Gerasimos EvangelatosGeorge E Fragoulis
Oct 28, 2019·Frontiers in Immunology·Michael D HowellPaul A Smith
Nov 30, 2019·Frontiers in Immunology·Dagmar GotthardtEva Maria Putz
Jun 17, 2020·Therapeutic Advances in Hematology·Ramzi AbboudJohn F DiPersio
Jun 13, 2020·Critical Care : the Official Journal of the Critical Care Forum·Irma ConvertinoCorrado Blandizzi
Jul 14, 2020·Frontiers in Immunology·Serena ColafrancescoRoberta Priori
Dec 24, 2019·Clinical Pharmacokinetics·Mohamed-Eslam F MohamedAhmed A Othman
Sep 26, 2020·Frontiers in Medicine·Leonard H CalabreseVibeke Strand
Sep 20, 2020·Inflammopharmacology·Genu GeorgeK G Raghu
Jul 16, 2020·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Margitta WormAikaterina Alexiou
Jun 20, 2020·Clinical Reviews in Allergy & Immunology·Jiao JiangQianjin Lu
Oct 11, 2020·International Journal of Molecular Sciences·Przemysław J KotylaMałgorzata Engelmann
Oct 29, 2020·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Margitta WormAikaterina Alexiou
Oct 30, 2020·Postgraduate Medicine·Jeffrey J CrowleyPaul S Yamauchi
Dec 2, 2020·International Journal of Molecular Sciences·Alexandra DamerauPaula Hoff
Dec 10, 2020·Expert Opinion on Drug Metabolism & Toxicology·Karima AlimOlivier Fardel
Oct 2, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eduardo HuartePaul A Smith
Dec 22, 2020·Immunology Letters·Paipai GuoQingtong Wang
Jan 23, 2021·Asia-Pacific Journal of Ophthalmology·Lisia Barros FerreiraJustine R Smith
Jan 21, 2021·Journal of Molecular Graphics & Modelling·Michela SpertiLuca Navarini

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Methods Mentioned

BETA
ESR

Clinical Trials Mentioned

NCT03101670
NCT03320876
NCT03104374
NCT03104400
NCT03117270
NCT03178487
NCT00617994
NCT01634087
NCT02812342
NCT02553330

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