{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:07:00Z","timestamp":1789960020336,"version":"4.0.1"},"reference-count":56,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","theclinics.com","gastro.theclinics.com","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Gastroenterology Clinics of North America"],"published-print":{"date-parts":[[2017,9]]},"DOI":"10.1016\/j.gtc.2017.05.015","type":"journal-article","created":{"date-parts":[[2017,8,25]],"date-time":"2017-08-25T18:49:03Z","timestamp":1503686943000},"page":"627-644","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":29,"title":["Janus Kinase Antagonists and Other Novel Small Molecules for the Treatment of Crohn's Disease"],"prefix":"10.1016","volume":"46","author":[{"given":"Brigid S.","family":"Boland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Vermeire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9317","key":"10.1016\/j.gtc.2017.05.015_bib1","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1016\/S0140-6736(02)08512-4","article-title":"Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial","volume":"359","author":"Hanauer","year":"2002","journal-title":"Lancet"},{"issue":"1","key":"10.1016\/j.gtc.2017.05.015_bib2","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1053\/j.gastro.2006.11.041","article-title":"Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial","volume":"132","author":"Colombel","year":"2007","journal-title":"Gastroenterology"},{"issue":"16","key":"10.1016\/j.gtc.2017.05.015_bib3","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1056\/NEJMoa1203572","article-title":"Ustekinumab induction and maintenance therapy in refractory Crohn's disease","volume":"367","author":"Sandborn","year":"2012","journal-title":"N\u00a0Engl J Med"},{"issue":"8","key":"10.1016\/j.gtc.2017.05.015_bib4","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1215739","article-title":"Vedolizumab as induction and maintenance therapy for Crohn's disease","volume":"369","author":"Sandborn","year":"2013","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.gtc.2017.05.015_bib5","unstructured":"Remicade [package insert]. Horsham, PA: Janssen Biotech, Inc; 2013."},{"issue":"11","key":"10.1016\/j.gtc.2017.05.015_bib6","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/nrd2445","article-title":"The influence of drug-like concepts on decision-making in medicinal chemistry","volume":"6","author":"Leeson","year":"2007","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"10.1016\/j.gtc.2017.05.015_bib7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/j.1524-4733.2007.00213.x","article-title":"Medication compliance and persistence: terminology and definitions","volume":"11","author":"Cramer","year":"2008","journal-title":"Value Health"},{"issue":"Suppl 2","key":"10.1016\/j.gtc.2017.05.015_bib8","doi-asserted-by":"crossref","first-page":"ii111","DOI":"10.1136\/annrheumdis-2012-202576","article-title":"Janus kinase inhibitors in autoimmune diseases","volume":"72","author":"O'Shea","year":"2013","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"10.1016\/j.gtc.2017.05.015_bib9","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S0952-7915(00)00228-4","article-title":"Signaling by type I and II cytokine receptors: ten years after","volume":"13","author":"Gadina","year":"2001","journal-title":"Curr Opin Immunol"},{"issue":"5332","key":"10.1016\/j.gtc.2017.05.015_bib10","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1126\/science.277.5332.1630","article-title":"STATs and gene regulation","volume":"277","author":"Darnell","year":"1997","journal-title":"Science"},{"issue":"5164","key":"10.1016\/j.gtc.2017.05.015_bib11","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1126\/science.8197455","article-title":"Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins","volume":"264","author":"Darnell","year":"1994","journal-title":"Science"},{"issue":"2","key":"10.1016\/j.gtc.2017.05.015_bib12","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nrgastro.2014.201","article-title":"IBD pathogenesis in 2014: molecular pathways controlling barrier function in IBD","volume":"12","author":"Atreya","year":"2015","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.gtc.2017.05.015_bib13","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/j.0105-2896.2004.00214.x","article-title":"IL-12 and IL-23: master regulators of innate and adaptive immunity","volume":"202","author":"Langrish","year":"2004","journal-title":"Immunol Rev"},{"issue":"6","key":"10.1016\/j.gtc.2017.05.015_bib14","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/00130832-200212000-00004","article-title":"Cytokines and their role in lymphoid development, differentiation and homeostasis","volume":"2","author":"Hofmann","year":"2002","journal-title":"Curr Opin Allergy Clin Immunol"},{"issue":"7422","key":"10.1016\/j.gtc.2017.05.015_bib15","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nature11582","article-title":"Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease","volume":"491","author":"Jostins","year":"2012","journal-title":"Nature"},{"issue":"7","key":"10.1016\/j.gtc.2017.05.015_bib16","doi-asserted-by":"crossref","first-page":"4234","DOI":"10.4049\/jimmunol.1003668","article-title":"Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550)","volume":"186","author":"Ghoreschi","year":"2011","journal-title":"J\u00a0Immunol"},{"key":"10.1016\/j.gtc.2017.05.015_bib17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1146\/annurev.immunol.16.1.293","article-title":"Jaks and STATs: biological implications","volume":"16","author":"Leonard","year":"1998","journal-title":"Annu Rev Immunol"},{"issue":"6","key":"10.1016\/j.gtc.2017.05.015_bib18","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1002\/art.34329","article-title":"The JAK inhibitor tofacitinib regulates synovitis through inhibition of interferon-gamma and interleukin-17 production by human CD4+ T\u00a0cells","volume":"64","author":"Maeshima","year":"2012","journal-title":"Arthritis Rheum"},{"issue":"3","key":"10.1016\/j.gtc.2017.05.015_bib19","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1136\/ard.2011.150284","article-title":"The JAK inhibitor CP-690,550 (tofacitinib) inhibits TNF-induced chemokine expression in fibroblast-like synoviocytes: autocrine role of type I interferon","volume":"71","author":"Rosengren","year":"2012","journal-title":"Ann Rheum Dis"},{"issue":"7","key":"10.1016\/j.gtc.2017.05.015_bib20","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1056\/NEJMoa1112168","article-title":"Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis","volume":"367","author":"Sandborn","year":"2012","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.gtc.2017.05.015_bib21","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMoa1606910","article-title":"Tofacitinib as induction and maintenance therapy for ulcerative colitis","volume":"376","author":"Sandborn","year":"2017","journal-title":"N Engl J Med"},{"issue":"9","key":"10.1016\/j.gtc.2017.05.015_bib22","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.cgh.2014.01.029","article-title":"A\u00a0phase 2 study of tofacitinib, an oral Janus kinase inhibitor, in patients with Crohn's disease","volume":"12","author":"Sandborn","year":"2014","journal-title":"Clin Gastroenterol Hepatol"},{"key":"10.1016\/j.gtc.2017.05.015_bib23","article-title":"Efficacy and safety of oral tofacitinib for induction therapy in patients with moderate-to-severe Crohns disease: results of a Phase 2b randomised placebo-controlled trial","author":"Pan\u00e9s","year":"2016","journal-title":"ECCO Congress"},{"key":"10.1016\/j.gtc.2017.05.015_bib24","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/1471-2474-14-298","article-title":"Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis","volume":"14","author":"He","year":"2013","journal-title":"BMC Musculoskelet Disord"},{"issue":"11","key":"10.1016\/j.gtc.2017.05.015_bib25","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1002\/art.38779","article-title":"Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis","volume":"66","author":"Cohen","year":"2014","journal-title":"Arthritis Rheumatol"},{"issue":"6","key":"10.1016\/j.gtc.2017.05.015_bib26","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1056\/NEJMoa1109071","article-title":"Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis","volume":"367","author":"Fleischmann","year":"2012","journal-title":"N\u00a0Engl J Med"},{"issue":"3","key":"10.1016\/j.gtc.2017.05.015_bib27","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.semarthrit.2016.05.014","article-title":"Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor","volume":"46","author":"Charles-Schoeman","year":"2016","journal-title":"Semin Arthritis Rheum"},{"issue":"10","key":"10.1016\/j.gtc.2017.05.015_bib28","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1002\/art.38745","article-title":"Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis","volume":"66","author":"Winthrop","year":"2014","journal-title":"Arthritis Rheumatol"},{"issue":"11","key":"10.1016\/j.gtc.2017.05.015_bib29","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1056\/NEJMoa1603800","article-title":"Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older","volume":"375","author":"Cunningham","year":"2016","journal-title":"N\u00a0Engl J Med"},{"issue":"5","key":"10.1016\/j.gtc.2017.05.015_bib30","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1136\/annrheumdis-2014-205847","article-title":"Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme","volume":"75","author":"Curtis","year":"2016","journal-title":"Ann Rheum Dis"},{"issue":"7","key":"10.1016\/j.gtc.2017.05.015_bib31","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.4049\/jimmunol.1201348","article-title":"Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases","volume":"191","author":"Van Rompaey","year":"2013","journal-title":"J\u00a0Immunol"},{"issue":"6","key":"10.1016\/j.gtc.2017.05.015_bib32","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1136\/annrheumdis-2016-210104","article-title":"Filgotinib (GLPG0634\/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1)","volume":"76","author":"Westhovens","year":"2016","journal-title":"Ann Rheum Dis"},{"issue":"10066","key":"10.1016\/j.gtc.2017.05.015_bib33","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/S0140-6736(16)32537-5","article-title":"Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial","volume":"389","author":"Vermeire","year":"2016","journal-title":"Lancet"},{"issue":"3","key":"10.1016\/j.gtc.2017.05.015_bib34","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1053\/j.gastro.2014.05.008","article-title":"Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed","volume":"147","author":"Sands","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.gtc.2017.05.015_bib35","unstructured":"Available at: clinicaltrials.gov. Accessed December 29, 2016."},{"key":"10.1016\/j.gtc.2017.05.015_bib36","doi-asserted-by":"crossref","first-page":"S1308","DOI":"10.1016\/S0016-5085(17)34357-3","article-title":"Safety and efficacy of upadacitinib (ABT-494), an oral JAK1 inhibitor, as induction therapy in patients with Crohn's disease: results from CELEST (abstract)","volume":"152","author":"Sandborn","year":"2017","journal-title":"Gastroenterology"},{"issue":"6659","key":"10.1016\/j.gtc.2017.05.015_bib37","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/37284","article-title":"TGF-beta signalling from cell membrane to nucleus through SMAD proteins","volume":"390","author":"Heldin","year":"1997","journal-title":"Nature"},{"issue":"17","key":"10.1016\/j.gtc.2017.05.015_bib38","doi-asserted-by":"crossref","first-page":"5353","DOI":"10.1093\/emboj\/16.17.5353","article-title":"TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4","volume":"16","author":"Nakao","year":"1997","journal-title":"EMBO J"},{"issue":"9","key":"10.1016\/j.gtc.2017.05.015_bib39","doi-asserted-by":"crossref","first-page":"5149","DOI":"10.4049\/jimmunol.172.9.5149","article-title":"Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T\u00a0cells through Foxp3 induction and down-regulation of Smad7","volume":"172","author":"Fantini","year":"2004","journal-title":"J\u00a0Immunol"},{"issue":"6651","key":"10.1016\/j.gtc.2017.05.015_bib40","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/39369","article-title":"Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling","volume":"389","author":"Nakao","year":"1997","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.gtc.2017.05.015_bib41","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1053\/gast.1996.v110.pm8613031","article-title":"Expression of transforming growth factors alpha and beta in colonic mucosa in inflammatory bowel disease","volume":"110","author":"Babyatsky","year":"1996","journal-title":"Gastroenterology"},{"issue":"4","key":"10.1016\/j.gtc.2017.05.015_bib42","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1172\/JCI12821","article-title":"Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease","volume":"108","author":"Monteleone","year":"2001","journal-title":"J\u00a0Clin Invest"},{"issue":"6","key":"10.1016\/j.gtc.2017.05.015_bib43","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1053\/j.gastro.2006.09.016","article-title":"Inhibition of Smad7 with a specific antisense oligonucleotide facilitates TGF-beta1-mediated suppression of colitis","volume":"131","author":"Boirivant","year":"2006","journal-title":"Gastroenterology"},{"issue":"4","key":"10.1016\/j.gtc.2017.05.015_bib44","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/mt.2011.290","article-title":"Phase I clinical trial of Smad7 knockdown using antisense oligonucleotide in patients with active Crohn's disease","volume":"20","author":"Monteleone","year":"2012","journal-title":"Mol Ther"},{"issue":"12","key":"10.1016\/j.gtc.2017.05.015_bib45","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1056\/NEJMoa1407250","article-title":"Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease","volume":"372","author":"Monteleone","year":"2015","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.gtc.2017.05.015_bib46","article-title":"A\u00a0Randomized, Double-blind, Multicenter Study to Explore the Efficacy of Oral GED-0301 (Mongersen) on Endoscopic Activity and Clinical Effects in Both TNF-Naive and TNF-Experienced Subjects with Active Crohn's Disease","author":"Feagan","year":"2016","journal-title":"United European Gastroenterology Week"},{"issue":"19","key":"10.1016\/j.gtc.2017.05.015_bib47","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1056\/NEJM199411103311907","article-title":"Transforming growth factor beta in tissue fibrosis","volume":"331","author":"Border","year":"1994","journal-title":"N\u00a0Engl J Med"},{"issue":"9","key":"10.1016\/j.gtc.2017.05.015_bib48","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1111\/apt.12051","article-title":"A\u00a0phase 1 open-label trial shows that smad7 antisense oligonucleotide (GED0301) does not increase the risk of small bowel strictures in Crohn's disease","volume":"36","author":"Zorzi","year":"2012","journal-title":"Aliment Pharmacol Ther"},{"key":"10.1016\/j.gtc.2017.05.015_bib49","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1146\/annurev.biochem.78.072407.103733","article-title":"Sphingosine 1-phosphate receptor signaling","volume":"78","author":"Rosen","year":"2009","journal-title":"Annu Rev Biochem"},{"issue":"4","key":"10.1016\/j.gtc.2017.05.015_bib50","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nrd2356","article-title":"Chemical modulators of sphingosine-1-phosphate receptors as barrier-oriented therapeutic molecules","volume":"8","author":"Marsolais","year":"2009","journal-title":"Nat Rev Drug Discov"},{"issue":"5566","key":"10.1016\/j.gtc.2017.05.015_bib51","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1126\/science.1070238","article-title":"Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists","volume":"296","author":"Mandala","year":"2002","journal-title":"Science"},{"issue":"16","key":"10.1016\/j.gtc.2017.05.015_bib52","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1212\/01.wnl.0000327609.57688.ea","article-title":"FTY720 therapy exerts differential effects on T\u00a0cell subsets in multiple sclerosis","volume":"71","author":"Mehling","year":"2008","journal-title":"Neurology"},{"issue":"5","key":"10.1016\/j.gtc.2017.05.015_bib53","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1056\/NEJMoa0909494","article-title":"A\u00a0placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis","volume":"362","author":"Kappos","year":"2010","journal-title":"N\u00a0Engl J Med"},{"issue":"11","key":"10.1016\/j.gtc.2017.05.015_bib54","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1111\/bph.13476","article-title":"Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity","volume":"173","author":"Scott","year":"2016","journal-title":"Br J Pharmacol"},{"issue":"18","key":"10.1016\/j.gtc.2017.05.015_bib55","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1056\/NEJMoa1513248","article-title":"Ozanimod induction and maintenance treatment for ulcerative colitis","volume":"374","author":"Sandborn","year":"2016","journal-title":"N\u00a0Engl J Med"},{"issue":"8","key":"10.1016\/j.gtc.2017.05.015_bib56","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1056\/NEJMc1607287","article-title":"Ozanimod treatment for ulcerative colitis","volume":"375","author":"Sandborn","year":"2016","journal-title":"N\u00a0Engl J Med"}],"container-title":["Gastroenterology Clinics of North America"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0889855317300699?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0889855317300699?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,8,28]],"date-time":"2018-08-28T05:00:28Z","timestamp":1535432428000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0889855317300699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["S0889855317300699"],"URL":"https:\/\/doi.org\/10.1016\/j.gtc.2017.05.015","relation":{},"ISSN":["0889-8553"],"issn-type":[{"value":"0889-8553","type":"print"}],"subject":[],"published":{"date-parts":[[2017,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Janus Kinase Antagonists and Other Novel Small Molecules for the Treatment of Crohn's Disease","name":"articletitle","label":"Article Title"},{"value":"Gastroenterology Clinics of North America","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.gtc.2017.05.015","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}