{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:12:50Z","timestamp":1791922370351,"version":"4.3.4"},"reference-count":117,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T00:00:00Z","timestamp":1575504000000},"content-version":"vor","delay-in-days":65,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2019,10]]},"DOI":"10.1016\/j.phrs.2019.104442","type":"journal-article","created":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T13:23:11Z","timestamp":1567516991000},"page":"104442","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":26,"special_numbering":"C","title":["Can molecular stratification improve the treatment of inflammatory bowel disease?"],"prefix":"10.1016","volume":"148","author":[{"given":"Claire","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M.","family":"Baer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Gaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.B.","family":"Nibbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Milling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"12","key":"10.1016\/j.phrs.2019.104442_bib0005","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nrgastro.2015.150","article-title":"The global burden of IBD: from 2015 to 2025","volume":"12","author":"Kaplan","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.phrs.2019.104442_bib0010","series-title":"What Is the Peak Age for Onset of IBD?","author":"Johnston","year":"2008"},{"issue":"1","key":"10.1016\/j.phrs.2019.104442_bib0015","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4110\/in.2017.17.1.25","article-title":"Pathogenesis of inflammatory bowel disease and recent advances in biologic therapies","volume":"17","author":"Kim","year":"2017","journal-title":"Immune Netw."},{"issue":"7","key":"10.1016\/j.phrs.2019.104442_bib0020","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2147\/JIR.S65979","article-title":"Inflammatory bowel disease: clinical aspects and treatments","author":"Fakhoury","year":"2014","journal-title":"J. Inflamm. Res."},{"key":"10.1016\/j.phrs.2019.104442_bib0025","first-page":"274","article-title":"Management of acute colitis and toxic megacolon","volume":"Vol 23","author":"Strong","year":"2010"},{"issue":"7","key":"10.1016\/j.phrs.2019.104442_bib0030","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.mayocp.2017.04.010","article-title":"Crohn disease: epidemiology, diagnosis, and management","volume":"92","author":"Feuerstein","year":"2017","journal-title":"Mayo Clin. Proc."},{"issue":"5","key":"10.1016\/j.phrs.2019.104442_bib0035","doi-asserted-by":"crossref","first-page":"363","DOI":"10.4240\/wjgs.v8.i5.363","article-title":"Inflammatory bowel disease surgery in the biologic era","volume":"8","author":"Ferrari","year":"2016","journal-title":"World J. Gastrointest. Surg."},{"key":"10.1016\/j.phrs.2019.104442_bib0040","first-page":"749","article-title":"Ulcerative Colitis : a challenge to surgeons","volume":"3","author":"Parray","year":"2012","journal-title":"Int. J. Prev. Med."},{"issue":"1","key":"10.1016\/j.phrs.2019.104442_bib0045","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1186\/s40064-015-1350-7","article-title":"Long-term outcomes of colectomy surgery among patients with ulcerative colitis","volume":"4","author":"Brown","year":"2015","journal-title":"Springerplus"},{"key":"10.1016\/j.phrs.2019.104442_bib0050","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1136\/bmj.320.7242.1119","article-title":"Regular review ulcerative colitis","volume":"320","author":"Ghosh","year":"2000","journal-title":"BMJ"},{"issue":"29","key":"10.1016\/j.phrs.2019.104442_bib0055","doi-asserted-by":"crossref","first-page":"9872","DOI":"10.3748\/wjg.v20.i29.9872","article-title":"Colorectal cancer in inflammatory bowel disease: the risk, pathogenesis, prevention and diagnosis","volume":"20","author":"Kim","year":"2014","journal-title":"World J. Gastroenterol."},{"issue":"4","key":"10.1016\/j.phrs.2019.104442_bib0060","first-page":"235","article-title":"Extraintestinal manifestations of inflammatory bowel disease","volume":"7","author":"Levine","year":"2011","journal-title":"Gastroenterol. Hepatol. (N Y)"},{"issue":"7","key":"10.1016\/j.phrs.2019.104442_bib0065","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1111\/j.1365-2036.2010.04234.x","article-title":"Systematic review: the costs of ulcerative colitis in Western countries","volume":"31","author":"Cohen","year":"2010","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"3","key":"10.1016\/j.phrs.2019.104442_bib0070","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cgh.2016.11.027","article-title":"Predicting Costs of Care for Patients With Inflammatory Bowel Diseases","volume":"15","author":"Click","year":"2017","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"3","key":"10.1016\/j.phrs.2019.104442_bib0075","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1136\/flgastro-2014-100514","article-title":"A UK cost of care model for inflammatory bowel disease","volume":"6","author":"Ghosh","year":"2015","journal-title":"Frontline Gastroenterol."},{"issue":"suppl_2","key":"10.1016\/j.phrs.2019.104442_bib0080","doi-asserted-by":"crossref","first-page":"S68","DOI":"10.1002\/ibd.20600","article-title":"How often do IBD patients require resection of their intestine?","volume":"14","author":"Hancock","year":"2008","journal-title":"Inflamm. Bowel Dis."},{"issue":"9","key":"10.1016\/j.phrs.2019.104442_bib0085","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1136\/gut.2010.234617","article-title":"Surgery for adult Crohn\u2019s disease: what is the actual risk?","volume":"60","author":"Bouguen","year":"2011","journal-title":"Gut"},{"key":"10.1016\/j.phrs.2019.104442_bib0090","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2015.00551","article-title":"Inflammatory bowel disease: genetics, epigenetics, and pathogenesis","volume":"6","author":"Loddo","year":"2015","journal-title":"Front. Immunol."},{"issue":"6","key":"10.1016\/j.phrs.2019.104442_bib0095","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.chom.2008.05.001","article-title":"Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases","volume":"3","author":"Peterson","year":"2008","journal-title":"Cell Host Microbe"},{"issue":"3","key":"10.1016\/j.phrs.2019.104442_bib0100","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.pharmthera.2012.10.008","article-title":"Immune aspects of the pathogenesis of inflammatory bowel disease","volume":"137","author":"Hisamatsu","year":"2013","journal-title":"Pharmacol. Ther."},{"issue":"1","key":"10.1016\/j.phrs.2019.104442_bib0105","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/14712598.2017.1258399","article-title":"Biological therapy targeting the IL-23\/IL-17 axis in inflammatory bowel disease","volume":"17","author":"Verstockt","year":"2017","journal-title":"Expert Opin. Biol. Ther."},{"key":"10.1016\/j.phrs.2019.104442_bib0110","first-page":"928461","article-title":"Role of Th17 cells in the pathogenesis of human IBD","volume":"2014","author":"G\u00e1lvez","year":"2014","journal-title":"ISRN Inflamm."},{"issue":"2","key":"10.1016\/j.phrs.2019.104442_bib0115","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1053\/j.gastro.2015.10.046","article-title":"Leukocyte trafficking to the small intestine and Colon","volume":"150","author":"Habtezion","year":"2016","journal-title":"Gastroenterology"},{"issue":"1","key":"10.1016\/j.phrs.2019.104442_bib0120","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0092-8674(93)90305-A","article-title":"\u03b14\u03b27 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1","volume":"74","author":"Berlin","year":"1993","journal-title":"Cell"},{"issue":"7422","key":"10.1016\/j.phrs.2019.104442_bib0125","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nature11582","article-title":"Host\u2013microbe interactions have shaped the genetic architecture of inflammatory bowel disease","volume":"491","author":"Jostins","year":"2012","journal-title":"Nature"},{"issue":"9","key":"10.1016\/j.phrs.2019.104442_bib0130","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/ng.3359","article-title":"Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations","volume":"47","author":"Liu","year":"2015","journal-title":"Nat. Genet."},{"issue":"43","key":"10.1016\/j.phrs.2019.104442_bib0135","doi-asserted-by":"crossref","first-page":"12296","DOI":"10.3748\/wjg.v21.i43.12296","article-title":"Genetics of inflammatory bowel disease from multifactorial to monogenic forms","volume":"21","author":"Bianco","year":"2015","journal-title":"World J. Gastroenterol."},{"issue":"6","key":"10.1016\/j.phrs.2019.104442_bib0140","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1053\/j.gastro.2011.02.046","article-title":"Recent Insights Into the Genetics of Inflammatory Bowel Disease","volume":"140","author":"Cho","year":"2016","journal-title":"Gastroenterology"},{"key":"10.1016\/j.phrs.2019.104442_bib0145","unstructured":"NICE. Recommendations | Ulcerative colitis: management | Guidance | NICE. https:\/\/www.nice.org.uk\/guidance\/cg166\/chapter\/1-Recommendations. Accessed March 8, 2019."},{"key":"10.1016\/j.phrs.2019.104442_bib0150","unstructured":"NICE. Recommendations | Crohn\u2019s disease: management | Guidance | NICE. https:\/\/www.nice.org.uk\/guidance\/cg152\/chapter\/Recommendations#maintaining-remission-in-crohns-disease. Accessed March 8, 2019."},{"key":"10.1016\/j.phrs.2019.104442_bib0155","series-title":"Guidelines for the Management of Inflammatory Bowel Disease in Adults","author":"Mowat","year":"2010"},{"key":"10.1016\/j.phrs.2019.104442_bib0160","series-title":"Lodotra 5 Mg Modified-release Tablets - Summary of Product Characteristics. Electronic Medicines Compendium","author":"ABPI","year":"2018"},{"key":"10.1016\/j.phrs.2019.104442_bib0165","unstructured":"NICE. Corticosteroids - oral. Clinical Knowledge Summaries. https:\/\/cks.nice.org.uk\/corticosteroids-oral#!scenario. Published 2017. Accessed March 8, 2019."},{"issue":"2","key":"10.1016\/j.phrs.2019.104442_bib0170","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2011.10.032","article-title":"Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis","volume":"142","author":"Sandborn","year":"2012","journal-title":"Gastroenterology"},{"issue":"3","key":"10.1016\/j.phrs.2019.104442_bib0175","first-page":"379","article-title":"Infliximab in ulcerative colitis","volume":"2","author":"Levin","year":"2008","journal-title":"Biol Targets Ther"},{"issue":"8","key":"10.1016\/j.phrs.2019.104442_bib0180","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMoa1215734","article-title":"Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis","volume":"369","author":"Feagan","year":"2013","journal-title":"N. Engl. J. Med."},{"issue":"8","key":"10.1016\/j.phrs.2019.104442_bib0185","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1215739","article-title":"Vedolizumab as Induction and Maintenance Therapy for Crohn\u2019s Disease","volume":"369","author":"Sandborn","year":"2013","journal-title":"N. Engl. J. Med."},{"issue":"16","key":"10.1016\/j.phrs.2019.104442_bib0190","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1056\/NEJMoa1203572","article-title":"Ustekinumab Induction and Maintenance Therapy in Refractory Crohn\u2019s Disease","volume":"367","author":"Sandborn","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.phrs.2019.104442_bib0195","series-title":"8-Week Induction Data From Pivotal Phase 3 UNIFI Study Presented During Plenary Session at the","author":"JANSSEN","year":"2018"},{"key":"10.1016\/j.phrs.2019.104442_bib0200","unstructured":"NICE. Overview | Tofacitinib for moderately to severely active ulcerative colitis | Guidance | NICE. https:\/\/www.nice.org.uk\/guidance\/ta547. Accessed May 29, 2019."},{"issue":"18","key":"10.1016\/j.phrs.2019.104442_bib0205","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."},{"key":"10.1016\/j.phrs.2019.104442_bib0210","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1016\/S0140-6736(02)08512-4","article-title":"Maintenance infliximab for Crohn\u2019s disease : the ACCENT I randomised trial for training purposes only. Not for promotional use. For training purposes only. Not for promotional use","volume":"359","author":"Hanauer","year":"2002","journal-title":"Lancet."},{"issue":"4","key":"10.1016\/j.phrs.2019.104442_bib0215","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1053\/j.gastro.2011.06.054","article-title":"Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis","volume":"141","author":"Colombel","year":"2011","journal-title":"Gastroenterology"},{"issue":"7","key":"10.1016\/j.phrs.2019.104442_bib0220","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1093\/ecco-jcc\/jjy040","article-title":"Colectomy rates in ulcerative colitis are low and decreasing: 10-year follow-up data from the Swiss IBD Cohort Study","volume":"12","author":"Parragi","year":"2018","journal-title":"J. Crohns Colitis"},{"issue":"5","key":"10.1016\/j.phrs.2019.104442_bib0225","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1053\/j.gastro.2013.07.041","article-title":"Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies","volume":"145","author":"Frolkis","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1016\/j.phrs.2019.104442_bib0230","unstructured":"NICE. 3 Clinical need and practice | Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel | Guidance | NICE. https:\/\/www.nice.org.uk\/guidance\/dg11\/chapter\/3-Clinical-need-and-practice. Accessed March 11, 2019."},{"issue":"12","key":"10.1016\/j.phrs.2019.104442_bib0235","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1172\/JCI200318921","article-title":"C-reactive protein: a critical update","volume":"111","author":"Pepys","year":"2003","journal-title":"J. Clin. Invest."},{"issue":"40","key":"10.1016\/j.phrs.2019.104442_bib0240","doi-asserted-by":"crossref","first-page":"11246","DOI":"10.3748\/wjg.v21.i40.11246","article-title":"Disease monitoring in inflammatory bowel disease","volume":"21","author":"Chang","year":"2015","journal-title":"World J. Gastroenterol."},{"issue":"4","key":"10.1016\/j.phrs.2019.104442_bib0245","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1053\/gast.2001.22546","article-title":"Comparative study of ASCA (Anti-Saccharomyces cerevisiae antibody) assays in inflammatory bowel disease","volume":"120","author":"Vermeire","year":"2001","journal-title":"Gastroenterology"},{"issue":"11","key":"10.1016\/j.phrs.2019.104442_bib0250","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1002\/ibd.20228","article-title":"Anti-Saccharomyces cerevisiae mannan antibodies (ASCA) of Crohn\u02bcs patients crossreact with mannan from other yeast strains, and murine ASCA IgM can be experimentally induced with Candida albicans","volume":"13","author":"Schaffer","year":"2007","journal-title":"Inflamm. Bowel Dis."},{"issue":"10","key":"10.1016\/j.phrs.2019.104442_bib0255","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1136\/gut.2006.108043","article-title":"New serological markers in inflammatory bowel disease are associated with complicated disease behaviour","volume":"56","author":"Ferrante","year":"2007","journal-title":"Gut"},{"issue":"9","key":"10.1016\/j.phrs.2019.104442_bib0260","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1097\/MIB.0000000000000460","article-title":"Neutrophil extracellular traps in ulcerative colitis: a proteome analysis of intestinal biopsies","volume":"21","author":"Bennike","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"issue":"5","key":"10.1016\/j.phrs.2019.104442_bib0265","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1136\/gut.49.5.671","article-title":"High level perinuclear antineutrophil cytoplasmic antibody (pANCA) in ulcerative colitis patients before colectomy predicts the development of chronic pouchitis after ileal pouch-anal anastomosis","volume":"49","author":"Fleshner","year":"2001","journal-title":"Gut"},{"issue":"7","key":"10.1016\/j.phrs.2019.104442_bib0270","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00296-005-0044-9","article-title":"The prevalence of extraintestinal manifestations and HLA association in patients with inflammatory bowel disease","volume":"26","author":"Turkcapar","year":"2006","journal-title":"Rheumatol. Int."},{"issue":"8","key":"10.1016\/j.phrs.2019.104442_bib0275","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1007\/s10620-009-0998-7","article-title":"Diagnostic role and clinical association of ASCA and ANCA in brazilian patients with inflammatory bowel disease","volume":"55","author":"Nisihara","year":"2010","journal-title":"Dig. Dis. Sci."},{"issue":"August","key":"10.1016\/j.phrs.2019.104442_bib0280","first-page":"1","article-title":"Frequencies of circulating regulatory TIGIT+CD38+ effector T cells correlate with the course of inflammatory bowel disease","author":"Joosse","year":"2018","journal-title":"Mucosal Immunol."},{"issue":"6","key":"10.1016\/j.phrs.2019.104442_bib0285","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/ajg.2011.24","article-title":"CD62L(neg)CD38+ expression on circulating CD4+ T cells identifies mucosally differentiated cells in protein fed mice and in human celiac disease patients and controls","volume":"106","author":"du Pr\u00e9","year":"2011","journal-title":"Am. J. Gastroenterol."},{"issue":"9","key":"10.1016\/j.phrs.2019.104442_bib0290","doi-asserted-by":"crossref","first-page":"793","DOI":"10.3109\/00365529209011186","article-title":"Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study","volume":"27","author":"R\u00f8seth","year":"1992","journal-title":"Scand. J. Gastroenterol."},{"issue":"1","key":"10.1016\/j.phrs.2019.104442_bib0295","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1053\/gast.2000.8523","article-title":"Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease","volume":"119","author":"Tibble","year":"2000","journal-title":"Gastroenterology"},{"issue":"8","key":"10.1016\/j.phrs.2019.104442_bib0300","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1111\/j.1572-0241.2008.01870.x","article-title":"Can calprotectin predict relapse risk in inflammatory bowel disease?","volume":"103","author":"D\u2019Inc\u00e0","year":"2008","journal-title":"Am. J. Gastroenterol."},{"issue":"8","key":"10.1016\/j.phrs.2019.104442_bib0305","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1002\/ibd.20933","article-title":"Fecal calprotectin and lactoferrin for the prediction of inflammatory bowel disease relapse","volume":"15","author":"Gisbert","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"issue":"9","key":"10.1016\/j.phrs.2019.104442_bib0310","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.crohns.2014.01.029","article-title":"A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn\u2019s disease","volume":"8","author":"Naismith","year":"2014","journal-title":"J. Crohns Colitis"},{"issue":"10","key":"10.1016\/j.phrs.2019.104442_bib0315","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1002\/ibd.22861","article-title":"Fecal calprotectin in predicting relapse of inflammatory bowel diseases: A meta-analysis of prospective studies","volume":"18","author":"Mao","year":"2012","journal-title":"Inflamm. Bowel Dis."},{"issue":"2","key":"10.1016\/j.phrs.2019.104442_bib0320","first-page":"134","article-title":"Commentary: Optimizing infliximab therapy for inflammatory bowel disease - The tools are getting sharper","volume":"8","author":"Dubeau","year":"2012","journal-title":"Gastroenterol. Hepatol."},{"issue":"6837","key":"10.1016\/j.phrs.2019.104442_bib0325","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/35079107","article-title":"Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn\u2019s disease","volume":"411","author":"Hugot","year":"2001","journal-title":"Nature"},{"issue":"6837","key":"10.1016\/j.phrs.2019.104442_bib0330","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/35079114","article-title":"A frameshift mutation in NOD2 associated with susceptibility to Crohn\u2019s disease","volume":"411","author":"Ogura","year":"2001","journal-title":"Nature"},{"issue":"50","key":"10.1016\/j.phrs.2019.104442_bib0335","doi-asserted-by":"crossref","first-page":"18129","DOI":"10.1073\/pnas.0505256102","article-title":"Reduced Paneth cell -defensins in ileal Crohn\u2019s disease","volume":"102","author":"Wehkamp","year":"2005","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"3","key":"10.1016\/j.phrs.2019.104442_bib0340","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1136\/gut.45.3.395","article-title":"HLA-DR and -DQ phenotypes in inflammatory bowel disease: a meta-analysis","volume":"45","author":"Stokkers","year":"1999","journal-title":"Gut"},{"issue":"12","key":"10.1016\/j.phrs.2019.104442_bib0345","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1097\/01.mib.0000235836.32176.5e","article-title":"Predictive value of the CARD15 variant 1007fs for the diagnosis of intestinal stenoses and the need for surgery in Crohn\u02bcs disease in clinical practice: Results of a Prospective Study","volume":"12","author":"Seiderer","year":"2006","journal-title":"Inflamm. Bowel Dis."},{"key":"10.1016\/j.phrs.2019.104442_bib0350","unstructured":"CCFA. Surgery for Crohn\u2019s Disease & Ulcerative Colitis | Crohn\u2019s & Colitis Foundation. http:\/\/www.crohnscolitisfoundation.org\/resources\/surgery-for-crohns-uc.html. Published 2010. Accessed September 18, 2018."},{"issue":"4","key":"10.1016\/j.phrs.2019.104442_bib0355","doi-asserted-by":"crossref","first-page":"322","DOI":"10.5217\/ir.2016.14.4.322","article-title":"Surgical management of inflammatory bowel disease in China: a systematic review of two decades","volume":"14","author":"Yu","year":"2016","journal-title":"Intest. Res."},{"issue":"3","key":"10.1016\/j.phrs.2019.104442_bib0360","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1136\/gut.2007.144865","article-title":"Molecular prediction of disease risk and severity in a large Dutch Crohn\u2019s disease cohort","volume":"58","author":"Weersma","year":"2009","journal-title":"Gut"},{"issue":"11","key":"10.1016\/j.phrs.2019.104442_bib0365","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1002\/ibd.21293","article-title":"Genetic predictors of medically refractory ulcerative colitis","volume":"16","author":"Haritunians","year":"2010","journal-title":"Inflamm. Bowel Dis."},{"issue":"10","key":"10.1016\/j.phrs.2019.104442_bib0370","doi-asserted-by":"crossref","first-page":"4170","DOI":"10.1172\/JCI59255","article-title":"Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis","volume":"121","author":"Lee","year":"2011","journal-title":"J. Clin. Invest."},{"issue":"7285","key":"10.1016\/j.phrs.2019.104442_bib0375","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature08821","article-title":"A human gut microbial gene catalogue established by metagenomic sequencing","volume":"464","author":"Qin","year":"2010","journal-title":"Nature"},{"issue":"5","key":"10.1016\/j.phrs.2019.104442_bib0380","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1097\/MIB.0000000000000023","article-title":"Decline in Presumptively Protective Gut Bacterial Species and Metabolites Are Paradoxically Associated with Disease Improvement in Pediatric Crohn\u2019s Disease During Enteral Nutrition","volume":"20","author":"Gerasimidis","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"issue":"7","key":"10.1016\/j.phrs.2019.104442_bib0385","doi-asserted-by":"crossref","first-page":"e6386","DOI":"10.1371\/journal.pone.0006386","article-title":"Metabolomics Reveals Metabolic Biomarkers of Crohn\u2019s Disease. Bereswill S, ed","volume":"4","author":"Jansson","year":"2009","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.phrs.2019.104442_bib0390","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12967-017-1175-y","article-title":"Influence of diet on the gut microbiome and implications for human health","volume":"15","author":"Singh","year":"2017","journal-title":"J. Transl. Med."},{"issue":"April","key":"10.1016\/j.phrs.2019.104442_bib0395","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/MIB.0000000000000036","article-title":"Alterations in the Intestinal Microbiome (Dysbiosis) as a Predictor of Relapse After Infliximab Withdrawal in Crohn\u02bcs Disease","author":"Rajca","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"10.1016\/j.phrs.2019.104442_bib0400","article-title":"Treatment of Active Crohn\u2019s Disease with an ordinary food-based diet that replicates exclusive enteral nutrition Q5","author":"Svolos","year":"2018","journal-title":"Gastroenterology"},{"issue":"10","key":"10.1016\/j.phrs.2019.104442_bib0405","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1111\/apt.12699","article-title":"Systematic review: faecal microbiota transplantation therapy for digestive and nondigestive disorders in adults and children","volume":"39","author":"Sha","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"6","key":"10.1016\/j.phrs.2019.104442_bib0410","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/apt.13736","article-title":"Systematic review: genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases","volume":"44","author":"Bek","year":"2016","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"1","key":"10.1016\/j.phrs.2019.104442_bib0415","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1136\/gut.49.1.35","article-title":"Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn\u2019s disease","volume":"49","author":"Itoh","year":"2001","journal-title":"Gut"},{"issue":"3","key":"10.1016\/j.phrs.2019.104442_bib0420","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0016-5085(99)70177-0","article-title":"Lamina propria T cells in Crohn\u2019s disease and other gastrointestinal inflammation show defective CD2 pathway-induced apoptosis","volume":"116","author":"Boirivant","year":"1999","journal-title":"Gastroenterology"},{"issue":"2","key":"10.1016\/j.phrs.2019.104442_bib0425","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1136\/gut.50.2.206","article-title":"Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn\u2019s disease","volume":"50","author":"ten Hove","year":"2002","journal-title":"Gut"},{"issue":"7","key":"10.1016\/j.phrs.2019.104442_bib0430","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/j.1365-2036.2005.02635.x","article-title":"Polymorphisms in apoptosis genes predict response to infliximab therapy in luminal and fistulizing Crohn\u2019s disease","volume":"22","author":"Hlavaty","year":"2005","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"27","key":"10.1016\/j.phrs.2019.104442_bib0435","doi-asserted-by":"crossref","first-page":"4958","DOI":"10.3748\/wjg.v23.i27.4958","article-title":"Genetic polymorphisms predict response to anti-tumor necrosis factor treatment in Crohn\u2019s disease","volume":"23","author":"Netz","year":"2017","journal-title":"World J. Gastroenterol."},{"issue":"14","key":"10.1016\/j.phrs.2019.104442_bib0440","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.2217\/pgs.13.146","article-title":"Association of TNF- \u03b1 polymorphism with prediction of response to TNF blockers in spondyloarthritis and inflammatory bowel disease: a meta-analysis","volume":"14","author":"Tong","year":"2013","journal-title":"Pharmacogenomics"},{"key":"10.1016\/j.phrs.2019.104442_bib0445","unstructured":"Genomics and Genome Editing in the NHS Third Report of Session 2017-19 Report, Together with Formal Minutes Relating to the Report.; 2018. www.parliament.uk\/science. Accessed May 29, 2019."},{"issue":"10","key":"10.1016\/j.phrs.2019.104442_bib0450","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/gim.2017.247","article-title":"Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature","volume":"20","author":"Schwarze","year":"2018","journal-title":"Genet. Med."},{"issue":"7","key":"10.1016\/j.phrs.2019.104442_bib0455","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/ajg.2011.83","article-title":"Gene expression profiling and response signatures associated with differential responses to infliximab treatment in ulcerative colitis","volume":"106","author":"Toedter","year":"2011","journal-title":"Am. J. Gastroenterol."},{"issue":"12","key":"10.1016\/j.phrs.2019.104442_bib0460","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1136\/gut.2009.178665","article-title":"Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis","volume":"58","author":"Arijs","year":"2009","journal-title":"Gut"},{"key":"10.1016\/j.phrs.2019.104442_bib0465","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.ebiom.2019.01.027","article-title":"Low TREM1 expression in whole blood predicts anti-TNF response in inflammatory bowel disease","volume":"40","author":"Verstockt","year":"2019","journal-title":"EBioMedicine"},{"issue":"July","key":"10.1016\/j.phrs.2019.104442_bib0470","article-title":"Mucosal gene expression changes induced by anti\u2010TNF treatment in inflammatory bowel disease patients","author":"Milanesi","year":"2019","journal-title":"Drug Dev. Res."},{"issue":"3","key":"10.1016\/j.phrs.2019.104442_bib0475","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nm.3462","article-title":"In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn\u2019s disease","volume":"20","author":"Atreya","year":"2014","journal-title":"Nat. Genet."},{"issue":"5","key":"10.1016\/j.phrs.2019.104442_bib0480","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nm.4307","article-title":"Oncostatin M drives intestinal inflammation in mice and its abundance predicts response to tumor necrosis factor- neutralizing therapy in patients with inflammatory bowel disease","volume":"23","author":"West","year":"2017","journal-title":"Nat. Med."},{"issue":"e000208","key":"10.1016\/j.phrs.2019.104442_bib0485","first-page":"1","article-title":"Putative biomarkers of vedolizumab resistance and underlying inflammatory pathways involved in IBD","volume":"5","author":"Soendergaard","year":"2018","journal-title":"BMJ Open Gastroenterol."},{"key":"10.1016\/j.phrs.2019.104442_bib0490","first-page":"1","article-title":"Recent advances: the imbalance of cytokines in the pathogenesis of inflammatory bowel disease","volume":"2017","author":"Guan","year":"2017","journal-title":"Mediators Inflamm."},{"issue":"8","key":"10.1016\/j.phrs.2019.104442_bib0495","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1093\/ecco-jcc\/jjw051","article-title":"Anti-TNF therapy response in patients with ulcerative colitis is associated with colonic antimicrobial peptide expression and microbiota composition","volume":"10","author":"Magnusson","year":"2016","journal-title":"J. Crohns Colitis"},{"issue":"1","key":"10.1016\/j.phrs.2019.104442_bib0500","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/ecco-jcc\/jju008","article-title":"Response to infliximab therapy in ulcerative colitis is associated with decreased monocyte activation, reduced CCL2 expression and downregulation of tenascin C","volume":"9","author":"Magnusson","year":"2015","journal-title":"J. Crohns Colitis"},{"issue":"11","key":"10.1016\/j.phrs.2019.104442_bib0505","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.it.2013.08.002","article-title":"The challenges of stratifying patients for trials in inflammatory bowel disease","volume":"34","author":"Biancheri","year":"2013","journal-title":"Trends Immunol."},{"key":"10.1016\/j.phrs.2019.104442_bib0510","first-page":"1","article-title":"Is top-down therapy a more effective alternative to conventional step-up therapy for Crohn\u2019s disease?","volume":"31","author":"Jenkin","year":"2018","journal-title":"Ann. Gastroenterol."},{"issue":"April","key":"10.1016\/j.phrs.2019.104442_bib0515","article-title":"Recently approved treatment","author":"Irwin","year":"2019","journal-title":"Crohn\u2019s Colitis Found"},{"issue":"2","key":"10.1016\/j.phrs.2019.104442_bib0520","article-title":"Fecal microbiota signatures are associated with response to ustekinumab therapy among Crohn\u2019s disease patients","volume":"9","author":"Doherty","year":"2018","journal-title":"Abstr. Gen. Meet. Am. Soc. Microbiol."},{"issue":"JUN","key":"10.1016\/j.phrs.2019.104442_bib0525","first-page":"1","article-title":"Functional characterization of novel Faecalibacterium prausnitzii strains isolated from healthy volunteers: A step forward in the use of F. prausnitzii as a next-generation probiotic","volume":"8","author":"Mart\u00edn","year":"2017","journal-title":"Front. Microbiol."},{"issue":"12","key":"10.1016\/j.phrs.2019.104442_bib0530","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1136\/gutjnl-2012-303956","article-title":"Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease","volume":"62","author":"Uhlig","year":"2013","journal-title":"Gut"},{"issue":"10","key":"10.1016\/j.phrs.2019.104442_bib0535","doi-asserted-by":"crossref","DOI":"10.1007\/s11882-016-0652-3","article-title":"Dysregulation of group 3 innate lymphoid cells in the pathogenesis of inflammatory bowel disease","volume":"16","author":"Forkel","year":"2016","journal-title":"Curr. Allergy Asthma Rep."},{"issue":"2","key":"10.1016\/j.phrs.2019.104442_bib0540","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00018-015-2055-3","article-title":"Innate lymphoid cells in intestinal immunity and inflammation","volume":"73","author":"Bostick","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.phrs.2019.104442_bib0545","doi-asserted-by":"crossref","unstructured":"Creyns B, Verstockt B, Cremer J, et al. Baseline ILC1 distribution in blood predicts response to ustekinumab in patients with refractory Crohn. ECCO, 7-9th Sep 2018, Vienna DOP018.","DOI":"10.1093\/ecco-jcc\/jjx180.055"},{"key":"10.1016\/j.phrs.2019.104442_bib0550","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1007\/s10620-018-4924-8","article-title":"Identification of Candidate Biomarkers Associated with Response to Vedolizumab in Inflammatory Bowel Disease","volume":"63","author":"Boden","year":"2018","journal-title":"Dig. Dis. Sci."},{"issue":"4","key":"10.1016\/j.phrs.2019.104442_bib0555","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/clpt.2011.328","article-title":"Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms","volume":"91","author":"Ord\u00e1s","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"issue":"4","key":"10.1016\/j.phrs.2019.104442_bib0560","first-page":"1","article-title":"Interactions between genetic variation and cellular environment in skeletal muscle gene expression","volume":"13","author":"Leland Taylor","year":"2018","journal-title":"PLoS One"},{"issue":"9","key":"10.1016\/j.phrs.2019.104442_bib0565","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.tig.2017.06.008","article-title":"Clinical genomics in inflammatory bowel disease","volume":"33","author":"Uhlig","year":"2017","journal-title":"Trends Genet."},{"issue":"2","key":"10.1016\/j.phrs.2019.104442_bib0570","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1053\/j.gastro.2012.04.045","article-title":"Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy","volume":"143","author":"Kotlarz","year":"2012","journal-title":"Gastroenterology"},{"issue":"5","key":"10.1016\/j.phrs.2019.104442_bib0575","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1016\/j.jaci.2016.10.022","article-title":"Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition","volume":"139","author":"Canna","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"issue":"5","key":"10.1016\/j.phrs.2019.104442_bib0580","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1053\/j.gastro.2014.07.023","article-title":"The diagnostic approach to monogenic very early onset inflammatory bowel disease","volume":"147","author":"Uhlig","year":"2014","journal-title":"Gastroenterology"},{"issue":"11","key":"10.1016\/j.phrs.2019.104442_bib0585","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1038\/ajg.2012.298","article-title":"Surgery in a population-based cohort of crohn\u2019s disease from Olmsted County, Minnesota (19702004)","volume":"107","author":"Peyrin-Biroulet","year":"2012","journal-title":"Am. J. Gastroenterol."}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S104366181931000X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S104366181931000X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T22:04:20Z","timestamp":1760911460000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S104366181931000X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10]]},"references-count":117,"alternative-id":["S104366181931000X"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2019.104442","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2019,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Can molecular stratification improve the treatment of inflammatory bowel disease?","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2019.104442","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"104442"}}