{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:05:51Z","timestamp":1792717551379,"version":"4.5.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr Gastroenterol Rep"],"published-print":{"date-parts":[[2015,6]]},"DOI":"10.1007\/s11894-015-0444-2","type":"journal-article","created":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T05:36:41Z","timestamp":1433137001000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Next-Generation Therapeutics for IBD"],"prefix":"10.1007","volume":"17","author":[{"given":"Mark","family":"L\u00f6wenberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"D\u2019Haens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,6,2]]},"reference":[{"key":"444_CR1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1053\/j.gastro.2006.11.041","volume":"132","author":"JF Colombel","year":"2007","unstructured":"Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn\u2019s disease: the CHARM trial. Gastroenterology. 2007;132:52\u201365.","journal-title":"Gastroenterology"},{"key":"444_CR2","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1016\/S0140-6736(02)08512-4","volume":"359","author":"SB Hanauer","year":"2002","unstructured":"Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Maintenance infliximab for Crohn\u2019s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541\u20139.","journal-title":"Lancet"},{"key":"444_CR3","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1056\/NEJMoa050516","volume":"353","author":"P Rutgeerts","year":"2005","unstructured":"Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462\u201376.","journal-title":"N Engl J Med"},{"key":"444_CR4","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1053\/j.gastro.2011.10.032","volume":"142","author":"WJ Sandborn","year":"2012","unstructured":"Sandborn WJ, van Gert A, Reinisch W, Colombel JF, D\u2019Haens G, Wolf DC, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:257\u201365.","journal-title":"Gastroenterology"},{"key":"444_CR5","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1053\/j.gastro.2013.05.048","volume":"146","author":"WJ Sandborn","year":"2014","unstructured":"Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:85\u201395. Induction trial with golimumab, a novel human monoclonal antibody against TNF, showed potent clinical efficacy compared to placebo in patients with moderate to severe active UC.","journal-title":"Gastroenterology"},{"key":"444_CR6","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.crohns.2010.04.004","volume":"4","author":"M Allez","year":"2010","unstructured":"Allez M, Karmiris K, Louis E, van Gert A, Ben-Horin S, Klein A, et al. Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: definitions, frequency and pharmacological aspects. J Crohns Colitis. 2010;4:355\u201366.","journal-title":"J Crohns Colitis"},{"key":"444_CR7","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/ajg.2010.392","volume":"106","author":"GR D\u2019Haens","year":"2011","unstructured":"D\u2019Haens GR, Panaccione R, Higgins PD, Vermeire S, Gassull M, Chowers Y, et al. The London position statement of the world congress of gastroenterology on biological therapy for IBD with the European Crohn\u2019s and colitis organization: when to start, when to stop, which drug to choose, and how to predict response? Am J Gastroenterol. 2011;106:199\u2013212.","journal-title":"Am J Gastroenterol"},{"key":"444_CR8","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1111\/j.1365-2036.2011.04612.x","volume":"33","author":"S Ben-Horin","year":"2011","unstructured":"Ben-Horin S, Chowers Y. Review article: loss of response to anti-TNF treatments in Crohn\u2019s disease. Aliment Pharmacol Ther. 2011;33:987\u201395.","journal-title":"Aliment Pharmacol Ther"},{"key":"444_CR9","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/ajg.2011.60","volume":"106","author":"V Billioud","year":"2011","unstructured":"Billioud V, Sandborn WJ, Peyrin-Biroulet L. Loss of response and need for adalimumab dose intensification in Crohn\u2019s disease: a systematic review. Am J Gastroenterol. 2011;106:674\u201384.","journal-title":"Am J Gastroenterol"},{"key":"444_CR10","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/ajg.2008.88","volume":"104","author":"JP Gisbert","year":"2009","unstructured":"Gisbert JP, Panes J. Loss of response and requirement of infliximab dose intensification in Crohn\u2019s disease: a review. Am J Gastroenterol. 2009;104:760\u20137.","journal-title":"Am J Gastroenterol"},{"key":"444_CR11","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1038\/ajg.2013.138","volume":"108","author":"AC Ford","year":"2013","unstructured":"Ford AC, Peyrin-Biroulet L. Opportunistic infections with anti-tumor necrosis factor-alpha therapy in inflammatory bowel disease: meta-analysis of randomized controlled trials. Am J Gastroenterol. 2013;108:1268\u201376.","journal-title":"Am J Gastroenterol"},{"key":"444_CR12","first-page":"261","volume":"59","author":"J Mill","year":"2013","unstructured":"Mill J, Lawrance IC. Prevention of cancer in. Minerva Gastroenterol Dietol. 2013;59:261\u201372.","journal-title":"Minerva Gastroenterol Dietol"},{"key":"444_CR13","doi-asserted-by":"crossref","first-page":"e449","DOI":"10.1016\/j.crohns.2013.02.019","volume":"7","author":"AJ Walsh","year":"2013","unstructured":"Walsh AJ, Weltman M, Burger D, Vivekanandarajah S, Connor S, Howlett M, et al. Implementing guidelines on the prevention of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2013;7:e449\u201356.","journal-title":"J Crohns Colitis"},{"key":"444_CR14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2147\/CEG.S48741","volume":"7","author":"M Lowenberg","year":"2014","unstructured":"Lowenberg M, de Boer NK, Hoentjen F. Golimumab for the treatment of ulcerative colitis. Clin Exp Gastroenterol. 2014;7:53\u20139.","journal-title":"Clin Exp Gastroenterol"},{"key":"444_CR15","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1053\/j.gastro.2013.06.010","volume":"146","author":"WJ Sandborn","year":"2014","unstructured":"Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:96\u2013109. Maintenance trial with subcutaneous golimumab in UC patients who responded to golimumab induction therapy. Golimumab treatment was able to maintain clinical responses through week 54 in significantly more patients as compared to placebo.","journal-title":"Gastroenterology"},{"key":"444_CR16","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1111\/apt.12712","volume":"39","author":"S Danese","year":"2014","unstructured":"Danese S, Siegel CA, Peyrin-Biroulet L. Review article: integrating budesonide-MMX into treatment algorithms for mild-to-moderate ulcerative colitis. Aliment Pharmacol Ther. 2014;39:1095\u2013103.","journal-title":"Aliment Pharmacol Ther"},{"key":"444_CR17","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1136\/gutjnl-2012-304258","volume":"63","author":"SP Travis","year":"2014","unstructured":"Travis SP, Danese S, Kupcinskas L, Alexeeva O, D\u2019Haens G, Gibson PR, et al. Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study. Gut. 2014;63:433\u201341.","journal-title":"Gut"},{"key":"444_CR18","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1053\/j.gastro.2012.08.003","volume":"143","author":"WJ Sandborn","year":"2012","unstructured":"Sandborn WJ, Travis S, Moro L, Jones R, Gautille T, Bagin R, et al. Once-daily budesonide MMX(R) extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology. 2012;143:1218\u201326.","journal-title":"Gastroenterology"},{"key":"444_CR19","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1056\/NEJMoa020696","volume":"348","author":"DH Miller","year":"2003","unstructured":"Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GP, Libonati MA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2003;348:15\u201323.","journal-title":"N Engl J Med"},{"key":"444_CR20","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1056\/NEJMoa043335","volume":"353","author":"WJ Sandborn","year":"2005","unstructured":"Sandborn WJ, Colombel JF, Enns R, Feagan BG, Hanauer SB, Lawrance IC, et al. Natalizumab induction and maintenance therapy for Crohn\u2019s disease. N Engl J Med. 2005;353:1912\u201325.","journal-title":"N Engl J Med"},{"key":"444_CR21","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1056\/NEJMoa1107829","volume":"366","author":"G Bloomgren","year":"2012","unstructured":"Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366:1870\u201380.","journal-title":"N Engl J Med"},{"key":"444_CR22","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMoa1215734","volume":"369","author":"BG Feagan","year":"2013","unstructured":"Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699\u2013710. Vedolizumab, the first gut-selective humanized monoclonal antibody (anti-\u03b14\u03b27), was evaluated in UC patients and proved to be more effective compared to placebo as induction and maintenance therapy.","journal-title":"N Engl J Med"},{"key":"444_CR23","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1215739","volume":"369","author":"WJ Sandborn","year":"2013","unstructured":"Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, et al. Vedolizumab as induction and maintenance therapy for Crohn\u2019s disease. N Engl J Med. 2013;369:711\u201321. Induction and maintenance trial with vedolizumab in CD showed that actively treated patients were more likely to achieve clinical remission, but not a CDAI-100 response, at week 6 versus placebo. Responders to induction therapy who continued vedolizumab were more likely to be in clinical remission at week 52.","journal-title":"N Engl J Med"},{"key":"444_CR24","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1053\/j.gastro.2014.05.008","volume":"147","author":"BE Sands","year":"2014","unstructured":"Sands BE, Feagan BG, Rutgeerts P, Colombel JF, Sandborn WJ, Sy R, et al. Effects of vedolizumab induction therapy for patients with Crohn\u2019s disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology. 2014;147:618\u201327. Induction trial with vedolizumab in CD patients who failed earlier treatment with anti-TNF agents. Vedolizumab was not more effective than placebo in inducing clinical remission at week 6, but therapeutic efficacy of the drug was detected at week 10.","journal-title":"Gastroenterology"},{"key":"444_CR25","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jneuroim.2013.08.011","volume":"264","author":"C Milch","year":"2013","unstructured":"Milch C, Wyant T, Xu J, Parikh A, Kent W, Fox I, et al. Vedolizumab, a monoclonal antibody to the gut homing alpha4beta7 integrin, does not affect cerebrospinal fluid T-lymphocyte immunophenotype. J Neuroimmunol. 2013;264:123\u20136.","journal-title":"J Neuroimmunol"},{"key":"444_CR26","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0140-6736(14)60661-9","volume":"384","author":"S Vermeire","year":"2014","unstructured":"Vermeire S, O\u2019Byrne S, Keir M, Williams M, Lu TT, Mansfield JC, et al. Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial. Lancet. 2014;384:309\u201318. Etrolizumab (humanised antibody against the \u03b27) was analyzed in UC patients and proved to be more effective in achieving clinical remission at week 10 as compared to placebo.","journal-title":"Lancet"},{"key":"444_CR27","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1136\/gut.2010.226548","volume":"60","author":"S Vermeire","year":"2011","unstructured":"Vermeire S, Ghosh S, Panes J, Dahlerup JF, Luegering A, Sirotiakova J, et al. The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised study. Gut. 2011;60:1068\u201375. The first-in-human study of PF-00547659 (monoclonal antibody against MAdCAM) in UC patients. Although, the drug produced potential benefits compared to placebo, no statistical differences were found between actively treated patients and placebo.","journal-title":"Gut"},{"key":"444_CR28","doi-asserted-by":"crossref","first-page":"e60094","DOI":"10.1371\/journal.pone.0060094","volume":"8","author":"S Keshav","year":"2013","unstructured":"Keshav S, Vanasek T, Niv Y, Petryka R, Howaldt S, Bafutto M, et al. A randomized controlled trial of the efficacy and safety of CCX282-B, an orally-administered blocker of chemokine receptor CCR9, for patients with Crohn\u2019s disease. PLoS One. 2013;8:e60094. CCX282-B (Vercirnon) was the first chemokine receptor antagonist to be tested in IBD. Although the primary endpoints were not achieved, the secondary endpoints were met in this study. Of note, these results in CD patients could not be reproduced in a large phase 3 trial that was entirely negative.","journal-title":"PLoS One"},{"key":"444_CR29","doi-asserted-by":"crossref","first-page":"504","DOI":"10.5312\/wjo.v5.i4.504","volume":"5","author":"LM Lundquist","year":"2014","unstructured":"Lundquist LM, Cole SW, Sikes ML. Efficacy and safety of tofacitinib for treatment of rheumatoid arthritis. World J Orthop. 2014;5:504\u201311.","journal-title":"World J Orthop"},{"key":"444_CR30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.tips.2010.10.004","volume":"32","author":"L Vijayakrishnan","year":"2011","unstructured":"Vijayakrishnan L, Venkataramanan R, Gulati P. Treating inflammation with the Janus kinase inhibitor CP-690,550. Trends Pharmacol Sci. 2011;32:25\u201334.","journal-title":"Trends Pharmacol Sci"},{"key":"444_CR31","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.2174\/13894501113149990160","volume":"14","author":"L Vuitton","year":"2013","unstructured":"Vuitton L, Koch S, Peyrin-Biroulet L. Janus kinase inhibition with tofacitinib: changing the face of inflammatory bowel disease treatment. Curr Drug Targets. 2013;14:1385\u201391.","journal-title":"Curr Drug Targets"},{"key":"444_CR32","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1056\/NEJMoa1112168","volume":"367","author":"WJ Sandborn","year":"2012","unstructured":"Sandborn WJ, Ghosh S, Panes J, Vranic I, Su C, Rousell S, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med. 2012;367:616\u201324. Tofacitinib is the first JAK inhibitor that has been evaluated in humans and proved to be effective in UC since actively treated patients were more likely to have clinical response and remission than those receiving placebo.","journal-title":"N Engl J Med"},{"key":"444_CR33","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.cgh.2014.01.029","volume":"12","author":"WJ Sandborn","year":"2014","unstructured":"Sandborn WJ, Ghosh S, Panes J, Vranic I, Wang W, Niezychowski W. A phase 2 study of tofacitinib, an oral Janus kinase inhibitor, in patients with Crohn\u2019s disease. Clin Gastroenterol Hepatol. 2014;12:1485\u201393. The primary endpoint was not met in this phase 2 trial in CD patients receiving tofacitinib, but the placebo response rate was high. Although no significant clinical differences were observed between actively treated patients and placebo, a reduction in CRP and fecal calprotectin levels among patients given 15 mg tofacitinib twice daily indicated its biologic activity.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"444_CR34","doi-asserted-by":"crossref","unstructured":"Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, III and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014.","DOI":"10.1002\/art.38779"},{"key":"444_CR35","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1056\/NEJMoa1104318","volume":"366","author":"G Comi","year":"2012","unstructured":"Comi G, Jeffery D, Kappos L, Montalban X, Boyko A, Rocca MA, et al. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med. 2012;366:1000\u20139.","journal-title":"N Engl J Med"},{"key":"444_CR36","doi-asserted-by":"crossref","unstructured":"D\u2019Haens G, Sandborn WJ, Colombel JF, Rutgeerts P, Brown K, Barkay H, Sakov A, Haviv A, Feagan BG. A phase II study of laquinimod in Crohn\u2019s disease. Gut. 2014. The small molecule laquinimod was analyzed in a dose escalation induction study in CD showing clinically efficacy versus placebo.","DOI":"10.1136\/gutjnl-2014-307118"}],"container-title":["Current Gastroenterology Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11894-015-0444-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11894-015-0444-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11894-015-0444-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,25]],"date-time":"2019-08-25T22:13:02Z","timestamp":1566771182000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11894-015-0444-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["444"],"URL":"https:\/\/doi.org\/10.1007\/s11894-015-0444-2","relation":{},"ISSN":["1522-8037","1534-312X"],"issn-type":[{"value":"1522-8037","type":"print"},{"value":"1534-312X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6]]},"article-number":"21"}}