{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:13:10Z","timestamp":1787850790788,"version":"build-2784847793"},"reference-count":97,"publisher":"Springer Science and Business Media LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,22]]},"DOI":"10.7759\/cureus.92901","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T08:54:10Z","timestamp":1758531250000},"source":"Crossref","is-referenced-by-count":4,"title":["A Comprehensive Review of the Role of Biologics and Small-Molecule Therapies in the Long-Term Management of Crohn\u2019s Disease"],"prefix":"10.7759","author":[{"given":"Syeda F","family":"Zaidi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keval B","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gabriela","family":"Cerdas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekanta","family":"Timalsina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abirami","family":"Rajendiran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duaa","family":"Behbehani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Mahmood","family":"Aljallawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gnaneswar","family":"Pendurthi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mounia N","family":"Bellaha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsion","family":"Gebregiorgis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Nazir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1186\/s13062-020-00280-5","article-title":"Pathophysiology of Crohn's disease inflammation and recurrence","volume":"15","author":"Petagna L","year":"2020","unstructured":"Petagna L, Antonelli A, Ganini C, et al.. Pathophysiology of Crohn's disease inflammation and recurrence. Biol Direct. 2020, 15:23. 10.1186\/s13062-020-00280-5","journal-title":"Biol Direct"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.07.003","article-title":"Incidence, prevalence, and racial and ethnic distribution of inflammatory bowel disease in the United States","volume":"165","author":"Lewis JD","year":"2023","unstructured":"Lewis JD, Parlett LE, Jonsson Funk ML, et al.. Incidence, prevalence, and racial and ethnic distribution of inflammatory bowel disease in the United States. Gastroenterology. 2023, 165:1197-1205.e2. 10.1053\/j.gastro.2023.07.003","journal-title":"Gastroenterology"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021526","article-title":"Pathophysiology of inflammatory bowel disease: innate immune system","volume":"24","author":"Saez A","year":"2023","unstructured":"Saez A, Herrero-Fernandez B, Gomez-Bris R, S\u00e1nchez-Martinez H, Gonzalez-Granado JM. Pathophysiology of inflammatory bowel disease: innate immune system. Int J Mol Sci. 2023, 24:1526. 10.3390\/ijms24021526","journal-title":"Int J Mol Sci"},{"key":"ref4","article-title":"Growth failure as a symptom of inflammatory bowel disease (Article in Dutch)","volume":"162","author":"de Kloet LC","year":"2018","unstructured":"de Kloet LC, Schagen SE, van den Berg A, Clement-de Boers A, Houdijk ME, van der Kaay DC. Growth failure as a symptom of inflammatory bowel disease (Article in Dutch). Ned Tijdschr Geneeskd. 2018, 162:2515.","journal-title":"Ned Tijdschr Geneeskd"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2025.01.002","article-title":"A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules","volume":"33","author":"Elmassry MM","year":"2025","unstructured":"Elmassry MM, Sugihara K, Chankhamjon P, et al.. A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules. Cell Host Microbe. 2025, 33:218-234.e12. 10.1016\/j.chom.2025.01.002","journal-title":"Cell Host Microbe"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.71","article-title":"Efficacy of 5-aminosalicylates in Crohn's disease: systematic review and meta-analysis","volume":"106","author":"Ford AC","year":"2011","unstructured":"Ford AC, Kane SV, Khan KJ, Achkar JP, Talley NJ, Marshall JK, Moayyedi P. Efficacy of 5-aminosalicylates in Crohn's disease: systematic review and meta-analysis. Am J Gastroenterol. 2011, 106:617-29. 10.1038\/ajg.2011.71","journal-title":"Am J Gastroenterol"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD000067.pub3","article-title":"Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn's disease","volume":"2015","author":"Chande N","year":"2015","unstructured":"Chande N, Patton PH, Tsoulis DJ, Thomas BS, MacDonald JK. Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2015, 2015:000067. 10.1002\/14651858.CD000067.pub3","journal-title":"Cochrane Database Syst Rev"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD000545","article-title":"Azathioprine or 6-mercaptopurine for inducing remission of Crohn's disease","author":"Sandborn W","year":"2000","unstructured":"Sandborn W, Sutherland L, Pearson D, May G, Modigliani R, Prantera C. Azathioprine or 6-mercaptopurine for inducing remission of Crohn's disease. Cochrane Database Syst Rev. 2000, 000545. 10.1002\/14651858.CD000545","journal-title":"Cochrane Database Syst Rev"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2018.27","article-title":"ACG clinical guideline: management of Crohn\u2019s disease in adults","volume":"113","author":"Lichtenstein GR","year":"2018","unstructured":"Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG clinical guideline: management of Crohn\u2019s disease in adults. Am J Gastroenterol. 2018, 113:481-517. 10.1038\/ajg.2018.27","journal-title":"Am J Gastroenterol"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.4240\/wjgs.v16.i5.1235","article-title":"Surgical treatment of inflammatory bowel disease: from the gastroenterologist's stand-point","volume":"16","author":"Triantafillidis JK","year":"2024","unstructured":"Triantafillidis JK. Surgical treatment of inflammatory bowel disease: from the gastroenterologist's stand-point. World J Gastrointest Surg. 2024, 16:1235-54. 10.4240\/wjgs.v16.i5.1235","journal-title":"World J Gastrointest Surg"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.2023-0493","article-title":"Crohn's disease: an update","volume":"23","author":"Cockburn E","year":"2023","unstructured":"Cockburn E, Kamal S, Chan A, Rao V, Liu T, Huang JY, Segal JP. Crohn's disease: an update. Clin Med (Lond). 2023, 23:549-57. 10.7861\/clinmed.2023-0493","journal-title":"Clin Med (Lond)"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-018-1479-6","article-title":"The state of the art on treatment of Crohn's disease","volume":"53","author":"Shi HY","year":"2018","unstructured":"Shi HY, Ng SC. The state of the art on treatment of Crohn's disease. J Gastroenterol. 2018, 53:989-98. 10.1007\/s00535-018-1479-6","journal-title":"J Gastroenterol"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.2147\/BTT.S71679","article-title":"Selective biologics for ulcerative colitis and Crohn's disease - clinical utility of vedolizumab","volume":"10","author":"Petkau JM","year":"2016","unstructured":"Petkau JM, Eksteen B. Selective biologics for ulcerative colitis and Crohn's disease - clinical utility of vedolizumab. Biologics. 2016, 10:33-52. 10.2147\/BTT.S71679","journal-title":"Biologics"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2014-307217","article-title":"Management of Crohn's disease","volume":"101","author":"Kammermeier J","year":"2016","unstructured":"Kammermeier J, Morris MA, Garrick V, Furman M, Rodrigues A, Russell RK. Management of Crohn's disease. Arch Dis Child. 2016, 101:475-80. 10.1136\/archdischild-2014-307217","journal-title":"Arch Dis Child"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0000000000001006","article-title":"Biologics, small molecule therapies and surgery in small bowel Crohn's disease","volume":"40","author":"Steinberg JM","year":"2024","unstructured":"Steinberg JM, Chowdhury R, Sharma S, Charabaty A. Biologics, small molecule therapies and surgery in small bowel Crohn's disease. Curr Opin Gastroenterol. 2024, 40:203-8. 10.1097\/MOG.0000000000001006","journal-title":"Curr Opin Gastroenterol"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/goac049","article-title":"Biologics: how far can they go in Crohn's disease?","volume":"10","author":"Dunleavy KA","year":"2022","unstructured":"Dunleavy KA, Pardi DS. Biologics: how far can they go in Crohn's disease?. Gastroenterol Rep (Oxf). 2022, 10:049. 10.1093\/gastro\/goac049","journal-title":"Gastroenterol Rep (Oxf)"},{"key":"ref17","article-title":"Crohn's disease: diagnosis and management","volume":"98","author":"Veauthier B","year":"2018","unstructured":"Veauthier B, Hornecker JR. Crohn's disease: diagnosis and management. Am Fam Physician. 2018, 98:661-9.","journal-title":"Am Fam Physician"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izad120","article-title":"Safety and monitoring of inflammatory bowel disease advanced therapies","volume":"30","author":"Bhat S","year":"2024","unstructured":"Bhat S, Click B, Regueiro M. Safety and monitoring of inflammatory bowel disease advanced therapies. Inflamm Bowel Dis. 2024, 30:829-43. 10.1093\/ibd\/izad120","journal-title":"Inflamm Bowel Dis"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15719","article-title":"Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn's disease","volume":"51","author":"Yang E","year":"2020","unstructured":"Yang E, Panaccione N, Whitmire N, et al.. Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn's disease. Aliment Pharmacol Ther. 2020, 51:1031-8. 10.1111\/apt.15719","journal-title":"Aliment Pharmacol Ther"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(23)00318-7","article-title":"Efficacy and safety of 48 weeks of guselkumab for patients with Crohn's disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial","volume":"9","author":"Danese S","year":"2024","unstructured":"Danese S, Panaccione R, Feagan BG, et al.. Efficacy and safety of 48 weeks of guselkumab for patients with Crohn's disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial. Lancet Gastroenterol Hepatol. 2024, 9:133-46. 10.1016\/S2468-1253(23)00318-7","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00466-4","article-title":"Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial","volume":"399","author":"Ferrante M","year":"2022","unstructured":"Ferrante M, Panaccione R, Baert F, et al.. Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet. 2022, 399:2031-46. 10.1016\/S0140-6736(22)00466-4","journal-title":"Lancet"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00467-6","article-title":"Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials","volume":"399","author":"D'Haens G","year":"2022","unstructured":"D'Haens G, Panaccione R, Baert F, et al.. Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022, 399:2015-30. 10.1016\/S0140-6736(22)00467-6","journal-title":"Lancet"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.10.050","article-title":"Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with Crohn\u2019s disease","volume":"162","author":"Sands BE","year":"2022","unstructured":"Sands BE, Peyrin-Biroulet L, Kierkus J, et al.. Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with Crohn\u2019s disease. Gastroenterology. 2022, 162:495-508. 10.1053\/j.gastro.2021.10.050","journal-title":"Gastroenterology"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3390\/ph14070637","article-title":"Small molecule drugs in inflammatory bowel diseases","volume":"14","author":"Ben Ghezala I","year":"2021","unstructured":"Ben Ghezala I, Charkaoui M, Michiels C, Bardou M, Luu M. Small molecule drugs in inflammatory bowel diseases. Pharmaceuticals (Basel). 2021, 14:637. 10.3390\/ph14070637","journal-title":"Pharmaceuticals (Basel)"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-397176-0.00005-4","article-title":"Chapter 5 - Similarities and differences in the discovery and use of biopharmaceuticals and small-molecule chemotherapeutics","author":"Samanen J","year":"2013","unstructured":"Samanen J. Chapter 5 - Similarities and differences in the discovery and use of biopharmaceuticals and small-molecule chemotherapeutics. Small Molecule Drug Research and Development. Ganellin R, Roberts S, Jefferis R (ed): Elsevier, Oxford (UK); 2013. 161-203. 10.1016\/B978-0-12-397176-0.00005-4"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2013.06.007","article-title":"Involvement of JAK\/STAT signaling in the pathogenesis of inflammatory bowel disease","volume":"76","author":"Coskun M","year":"2013","unstructured":"Coskun M, Salem M, Pedersen J, Nielsen OH. Involvement of JAK\/STAT signaling in the pathogenesis of inflammatory bowel disease. Pharmacol Res. 2013, 76:1-8. 10.1016\/j.phrs.2013.06.007","journal-title":"Pharmacol Res"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.11.015","article-title":"JAK\/STAT-1 signaling is required for reserve intestinal stem cell activation during intestinal regeneration following acute inflammation","volume":"10","author":"Richmond CA","year":"2018","unstructured":"Richmond CA, Rickner H, Shah MS, et al.. JAK\/STAT-1 signaling is required for reserve intestinal stem cell activation during intestinal regeneration following acute inflammation. Stem Cell Reports. 2018, 10:17-26. 10.1016\/j.stemcr.2017.11.015","journal-title":"Stem Cell Reports"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-62652-3.00004-1","article-title":"Advances in the discovery of selective JAK inhibitors","volume":"52","author":"Menet CJ","year":"2013","unstructured":"Menet CJ, Rompaey LV, Geney R. Advances in the discovery of selective JAK inhibitors. Prog Med Chem. 2013, 52:153-223. 10.1016\/B978-0-444-62652-3.00004-1","journal-title":"Prog Med Chem"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastro.2005.05.002","article-title":"Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution","volume":"129","author":"Heller F","year":"2005","unstructured":"Heller F, Florian P, Bojarski C, et al.. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology. 2005, 129:550-64. 10.1016\/j.gastro.2005.05.002","journal-title":"Gastroenterology"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.201","article-title":"JAK inhibition as a therapeutic strategy for immune and inflammatory diseases","volume":"16","author":"Schwartz DM","year":"2017","unstructured":"Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017, 16:843-62. 10.1038\/nrd.2017.201","journal-title":"Nat Rev Drug Discov"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000001730","article-title":"Small molecule drugs in the treatment of inflammatory bowel diseases: which one, when and why? - a systematic review","volume":"32","author":"Lucaciu LA","year":"2020","unstructured":"Lucaciu LA, Seicean R, Seicean A. Small molecule drugs in the treatment of inflammatory bowel diseases: which one, when and why? - a systematic review. Eur J Gastroenterol Hepatol. 2020, 32:669-77. 10.1097\/MEG.0000000000001730","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00311.2015","article-title":"JAK inhibition using tofacitinib for inflammatory bowel disease treatment: a hub for multiple inflammatory cytokines","volume":"310","author":"Danese S","year":"2016","unstructured":"Danese S, Grisham M, Hodge J, Telliez JB. JAK inhibition using tofacitinib for inflammatory bowel disease treatment: a hub for multiple inflammatory cytokines. Am J Physiol Gastrointest Liver Physiol. 2016, 310:155-62. 10.1152\/ajpgi.00311.2015","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312735","article-title":"Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials","volume":"66","author":"Pan\u00e9s J","year":"2017","unstructured":"Pan\u00e9s J, Sandborn WJ, Schreiber S, et al.. Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials. Gut. 2017, 66:1049-59. 10.1136\/gutjnl-2016-312735","journal-title":"Gut"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15072","article-title":"Long-term safety and tolerability of oral tofacitinib in patients with Crohn's disease: results from a phase 2, open-label, 48-week extension study","volume":"49","author":"Pan\u00e9s J","year":"2019","unstructured":"Pan\u00e9s J, D'Haens GR, Higgins PD, et al.. Long-term safety and tolerability of oral tofacitinib in patients with Crohn's disease: results from a phase 2, open-label, 48-week extension study. Aliment Pharmacol Ther. 2019, 49:265-76. 10.1111\/apt.15072","journal-title":"Aliment Pharmacol Ther"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0605-6","article-title":"Population pharmacokinetics of upadacitinib in healthy subjects and subjects with rheumatoid arthritis: analyses of phase I and II clinical trials","volume":"57","author":"Kl\u00fcnder B","year":"2018","unstructured":"Kl\u00fcnder B, Mohamed MF, Othman AA. Population pharmacokinetics of upadacitinib in healthy subjects and subjects with rheumatoid arthritis: analyses of phase I and II clinical trials. Clin Pharmacokinet. 2018, 57:977-88. 10.1007\/s40262-017-0605-6","journal-title":"Clin Pharmacokinet"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.01.047","article-title":"Efficacy and safety of upadacitinib in a randomized trial of patients with Crohn\u2019s disease","volume":"158","author":"Sandborn WJ","year":"2020","unstructured":"Sandborn WJ, Feagan BG, Loftus EV Jr, et al.. Efficacy and safety of upadacitinib in a randomized trial of patients with Crohn\u2019s disease. Gastroenterology. 2020, 158:2123-2138.e8. 10.1053\/j.gastro.2020.01.047","journal-title":"Gastroenterology"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjae003","article-title":"Efficacy and safety of filgotinib for the treatment of perianal fistulising Crohn\u2019s disease [divergence 2]: a phase 2, randomised, placebo-controlled trial","volume":"18","author":"Reinisch W","year":"2024","unstructured":"Reinisch W, Colombel JF, D'Haens GR, et al.. Efficacy and safety of filgotinib for the treatment of perianal fistulising Crohn\u2019s disease [divergence 2]: a phase 2, randomised, placebo-controlled trial. J Crohns Colitis. 2024, 18:864-74. 10.1093\/ecco-jcc\/jjae003","journal-title":"J Crohns Colitis"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2016.160","article-title":"Sphingosine 1-phosphate receptor modulators and drug discovery","volume":"25","author":"Park SJ","year":"2017","unstructured":"Park SJ, Im DS. Sphingosine 1-phosphate receptor modulators and drug discovery. Biomol Ther (Seoul). 2017, 25:80-90. 10.4062\/biomolther.2016.160","journal-title":"Biomol Ther (Seoul)"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izy269","article-title":"Cell trafficking interference in inflammatory bowel disease: therapeutic interventions based on basic pathogenesis concepts","volume":"25","author":"P\u00e9rez-Jeldres T","year":"2019","unstructured":"P\u00e9rez-Jeldres T, Tyler CJ, Boyer JD, et al.. Cell trafficking interference in inflammatory bowel disease: therapeutic interventions based on basic pathogenesis concepts. Inflamm Bowel Dis. 2019, 25:270-82. 10.1093\/ibd\/izy269","journal-title":"Inflamm Bowel Dis"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2017.03.007","article-title":"Modulation of sphingosine-1-phosphate in inflammatory bowel disease","volume":"16","author":"Peyrin-Biroulet L","year":"2017","unstructured":"Peyrin-Biroulet L, Christopher R, Behan D, Lassen C. Modulation of sphingosine-1-phosphate in inflammatory bowel disease. Autoimmun Rev. 2017, 16:495-503. 10.1016\/j.autrev.2017.03.007","journal-title":"Autoimmun Rev"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(20)30188-6","article-title":"Ozanimod induction therapy for patients with moderate to severe Crohn's disease: a single-arm, phase 2, prospective observer-blinded endpoint study","volume":"5","author":"Feagan BG","year":"2020","unstructured":"Feagan BG, Sandborn WJ, Danese S, et al.. Ozanimod induction therapy for patients with moderate to severe Crohn's disease: a single-arm, phase 2, prospective observer-blinded endpoint study. Lancet Gastroenterol Hepatol. 2020, 5:819-28. 10.1016\/S2468-1253(20)30188-6","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i17.1868","article-title":"Anti-integrin therapy for inflammatory bowel disease","volume":"24","author":"Park SC","year":"2018","unstructured":"Park SC, Jeen YT. Anti-integrin therapy for inflammatory bowel disease. World J Gastroenterol. 2018, 24:1868-80. 10.3748\/wjg.v24.i17.1868","journal-title":"World J Gastroenterol"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006097","article-title":"Natalizumab for induction of remission in Crohn's disease","author":"Macdonald JK","year":"2006","unstructured":"Macdonald JK, McDonald JW. Natalizumab for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2006, 006097. 10.1002\/14651858.CD006097","journal-title":"Cochrane Database Syst Rev"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.946","article-title":"Single- and multiple-dose pharmacokinetics and pharmacodynamics of PN-943, a gastrointestinal-restricted oral peptide antagonist of \u03b14\u03b27, in healthy volunteers","volume":"10","author":"Modi NB","year":"2021","unstructured":"Modi NB, Cheng X, Mattheakis L, Hwang CC, Nawabi R, Liu D, Gupta S. Single- and multiple-dose pharmacokinetics and pharmacodynamics of PN-943, a gastrointestinal-restricted oral peptide antagonist of \u03b14\u03b27, in healthy volunteers. Clin Pharmacol Drug Dev. 2021, 10:1263-78. 10.1002\/cpdd.946","journal-title":"Clin Pharmacol Drug Dev"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2018.1494722","article-title":"PF-00547659 for the treatment of Crohn's disease and ulcerative colitis","volume":"27","author":"Allocca M","year":"2018","unstructured":"Allocca M, Gilardi D, Fiorino G, Furfaro F, Argollo M, Peyrin-Biroulet L, Danese S. PF-00547659 for the treatment of Crohn's disease and ulcerative colitis. Expert Opin Investig Drugs. 2018, 27:623-9. 10.1080\/13543784.2018.1494722","journal-title":"Expert Opin Investig Drugs"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30930-3","article-title":"Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trial","volume":"390","author":"Vermeire S","year":"2017","unstructured":"Vermeire S, Sandborn WJ, Danese S, et al.. Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2017, 390:135-44. 10.1016\/S0140-6736(17)30930-3","journal-title":"Lancet"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-313457","article-title":"Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn's disease: report of the OPERA study","volume":"67","author":"Sandborn WJ","year":"2018","unstructured":"Sandborn WJ, Lee SD, Tarabar D, et al.. Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn's disease: report of the OPERA study. Gut. 2018, 67:1824-35. 10.1136\/gutjnl-2016-313457","journal-title":"Gut"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjab023","article-title":"Long-term safety and efficacy of the anti-MAdCAM-1 monoclonal antibody ontamalimab [SHP647] for the treatment of ulcerative colitis: the open-label study turandot II","volume":"15","author":"Reinisch W","year":"2021","unstructured":"Reinisch W, Sandborn WJ, Danese S, et al.. Long-term safety and efficacy of the anti-MAdCAM-1 monoclonal antibody ontamalimab [SHP647] for the treatment of ulcerative colitis: the open-label study turandot II. J Crohns Colitis. 2021, 15:938-49. 10.1093\/ecco-jcc\/jjab023","journal-title":"J Crohns Colitis"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18061276","article-title":"PDE4 inhibition and inflammatory bowel disease: a novel therapeutic avenue","volume":"18","author":"Spadaccini M","year":"2017","unstructured":"Spadaccini M, D'Alessio S, Peyrin-Biroulet L, Danese S. PDE4 inhibition and inflammatory bowel disease: a novel therapeutic avenue. Int J Mol Sci. 2017, 18:1276. 10.3390\/ijms18061276","journal-title":"Int J Mol Sci"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.11.029","article-title":"A randomized, placebo-controlled, phase II study of tetomilast in active ulcerative colitis","volume":"132","author":"Schreiber S","year":"2007","unstructured":"Schreiber S, Keshavarzian A, Isaacs KL, Schollenberger J, Guzman JP, Orlandi C, Hanauer SB. A randomized, placebo-controlled, phase II study of tetomilast in active ulcerative colitis. Gastroenterology. 2007, 132:76-86. 10.1053\/j.gastro.2006.11.029","journal-title":"Gastroenterology"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.12.032","article-title":"Effects of apremilast, an oral inhibitor of phosphodiesterase 4, in a randomized trial of patients with active ulcerative colitis","volume":"18","author":"Danese S","year":"2020","unstructured":"Danese S, Neurath MF, Kopo\u0144 A, et al.. Effects of apremilast, an oral inhibitor of phosphodiesterase 4, in a randomized trial of patients with active ulcerative colitis. Clin Gastroenterol Hepatol. 2020, 18:2526-2534.e9. 10.1016\/j.cgh.2019.12.032","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2008.55","article-title":"TGF-beta1 and Smad7 in the regulation of IBD","volume":"1","author":"Monteleone G","year":"2008","unstructured":"Monteleone G, Boirivant M, Pallone F, MacDonald TT. TGF-beta1 and Smad7 in the regulation of IBD. Mucosal Immunol. 2008, 1:50-3. 10.1038\/mi.2008.55","journal-title":"Mucosal Immunol"},{"key":"ref53","doi-asserted-by":"publisher","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 M","year":"2006","unstructured":"Boirivant M, Pallone F, Di Giacinto C, et al.. Inhibition of Smad7 with a specific antisense oligonucleotide facilitates TGF-beta1-mediated suppression of colitis. Gastroenterology. 2006, 131:1786-98. 10.1053\/j.gastro.2006.09.016","journal-title":"Gastroenterology"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407250","article-title":"Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease","volume":"372","author":"Monteleone G","year":"2015","unstructured":"Monteleone G, Neurath MF, Ardizzone S, et al.. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease. N Engl J Med. 2015, 372:1104-13. 10.1056\/NEJMoa1407250","journal-title":"N Engl J Med"},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000493","article-title":"Mongersen (GED-0301) for active Crohn\u2019s disease: results of a phase 3 study","volume":"115","author":"Sands BE","year":"2020","unstructured":"Sands BE, Feagan BG, Sandborn WJ, et al.. Mongersen (GED-0301) for active Crohn\u2019s disease: results of a phase 3 study. Am J Gastroenterol. 2020, 115:738-45. 10.14309\/ajg.0000000000000493","journal-title":"Am J Gastroenterol"},{"key":"ref56","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102129","article-title":"Vidofludimus calcium, a next generation DHODH inhibitor for the treatment of relapsing-remitting multiple sclerosis","volume":"43","author":"Muehler A","year":"2020","unstructured":"Muehler A, Peelen E, Kohlhof H, Gr\u00f6ppel M, Vitt D. Vidofludimus calcium, a next generation DHODH inhibitor for the treatment of relapsing-remitting multiple sclerosis. Mult Scler Relat Disord. 2020, 43:102129. 10.1016\/j.msard.2020.102129","journal-title":"Mult Scler Relat Disord"},{"key":"ref57","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-019-00286-z","article-title":"The selective oral immunomodulator Vidofludimus in patients with active rheumatoid arthritis: safety results from the component study","volume":"19","author":"Muehler A","year":"2019","unstructured":"Muehler A, Kohlhof H, Groeppel M, Vitt D. The selective oral immunomodulator Vidofludimus in patients with active rheumatoid arthritis: safety results from the component study. Drugs R D. 2019, 19:351-66. 10.1007\/s40268-019-00286-z","journal-title":"Drugs R D"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-020-00623-7","article-title":"Safety, tolerability and pharmacokinetics of vidofludimus calcium (IMU-838) after single and multiple ascending oral doses in healthy male subjects","volume":"45","author":"Muehler A","year":"2020","unstructured":"Muehler A, Kohlhof H, Groeppel M, Vitt D. Safety, tolerability and pharmacokinetics of vidofludimus calcium (IMU-838) after single and multiple ascending oral doses in healthy male subjects. Eur J Drug Metab Pharmacokinet. 2020, 45:557-73. 10.1007\/s13318-020-00623-7","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"ref59","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2009.12.003","article-title":"The second European evidence-based consensus on the diagnosis and management of Crohn's disease: definitions and diagnosis","volume":"4","author":"Van Assche G","year":"2010","unstructured":"Van Assche G, Dignass A, Panes J, et al.. The second European evidence-based consensus on the diagnosis and management of Crohn's disease: definitions and diagnosis. J Crohns Colitis. 2010, 4:7-27. 10.1016\/j.crohns.2009.12.003","journal-title":"J Crohns Colitis"},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006893","article-title":"Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn's disease","author":"Behm BW","year":"2008","unstructured":"Behm BW, Bickston SJ. Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2008, 006893. 10.1002\/14651858.CD006893","journal-title":"Cochrane Database Syst Rev"},{"key":"ref61","doi-asserted-by":"publisher","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 JF","year":"2007","unstructured":"Colombel JF, Sandborn WJ, Rutgeerts P, et al.. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology. 2007, 132:52-65. 10.1053\/j.gastro.2006.11.041","journal-title":"Gastroenterology"},{"key":"ref62","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062897","article-title":"Maintenance therapy with certolizumab pegol for Crohn's disease","volume":"357","author":"Schreiber S","year":"2007","unstructured":"Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al.. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007, 357:239-50. 10.1056\/NEJMoa062897","journal-title":"N Engl J Med"},{"key":"ref63","doi-asserted-by":"publisher","DOI":"10.4166\/kjg.2024.064","article-title":"Small molecule therapy for inflammatory bowel disease: JAK inhibitors and S1PR modulators (Article in Korean)","volume":"84","author":"Jun YK","year":"2024","unstructured":"Jun YK, Yoon H. Small molecule therapy for inflammatory bowel disease: JAK inhibitors and S1PR modulators (Article in Korean). Korean J Gastroenterol. 2024, 84:51-64. 10.4166\/kjg.2024.064","journal-title":"Korean J Gastroenterol"},{"key":"ref64","doi-asserted-by":"publisher","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":"266","author":"Vermeire S","year":"2017","unstructured":"Vermeire S, Schreiber S, Petryka R, et al.. 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. Lancet. 2017, 266:75. 10.1016\/S0140-6736(16)32537-5","journal-title":"Lancet"},{"key":"ref65","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjz186","article-title":"Efficacy of JAK inhibitors in Crohn's disease","volume":"14","author":"Rogler G","year":"2020","unstructured":"Rogler G. Efficacy of JAK inhibitors in Crohn's disease. J Crohns Colitis. 2020, 14:746-54. 10.1093\/ecco-jcc\/jjz186","journal-title":"J Crohns Colitis"},{"key":"ref66","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2013.10.001","article-title":"Drug delivery strategies in the therapy of inflammatory bowel disease","volume":"71","author":"Lautenschl\u00e4ger C","year":"2014","unstructured":"Lautenschl\u00e4ger C, Schmidt C, Fischer D, Stallmach A. Drug delivery strategies in the therapy of inflammatory bowel disease. Adv Drug Deliv Rev. 2014, 71:58-76. 10.1016\/j.addr.2013.10.001","journal-title":"Adv Drug Deliv Rev"},{"key":"ref67","doi-asserted-by":"publisher","DOI":"10.1016\/s1286-4579(01)01476-9","article-title":"Microbiological and immunological strategies for treatment of inflammatory bowel disease","volume":"3","author":"Steidler L","year":"2001","unstructured":"Steidler L. Microbiological and immunological strategies for treatment of inflammatory bowel disease. Microbes Infect. 2001, 3:1157-66. 10.1016\/s1286-4579(01)01476-9","journal-title":"Microbes Infect"},{"key":"ref68","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000002850","article-title":"Systematic review with meta-analysis of the effectiveness of subcutaneous biologics versus intravenous biologics in inflammatory bowel diseases","volume":"37","author":"Elford AT","year":"2025","unstructured":"Elford AT, Heldt R, Kamal S, Christensen B, Segal JP. Systematic review with meta-analysis of the effectiveness of subcutaneous biologics versus intravenous biologics in inflammatory bowel diseases. Eur J Gastroenterol Hepatol. 2025, 37:47-54. 10.1097\/MEG.0000000000002850","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"ref69","article-title":"Sphingosine-1 phosphate receptor modulators: the next wave of oral therapies in inflammatory bowel disease","volume":"18","author":"Choden T","year":"2022","unstructured":"Choden T, Cohen NA, Rubin DT. Sphingosine-1 phosphate receptor modulators: the next wave of oral therapies in inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2022, 18:265-71.","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"ref70","doi-asserted-by":"publisher","DOI":"10.1517\/17425247.2012.730517","article-title":"Oral colon-specific therapeutic approaches toward treatment of inflammatory bowel disease","volume":"9","author":"Xiao B","year":"2012","unstructured":"Xiao B, Merlin D. Oral colon-specific therapeutic approaches toward treatment of inflammatory bowel disease. Expert Opin Drug Deliv. 2012, 9:1393-407. 10.1517\/17425247.2012.730517","journal-title":"Expert Opin Drug Deliv"},{"key":"ref71","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08512-4","article-title":"Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial","volume":"4","author":"Hanauer SB","year":"2002","unstructured":"Hanauer SB, Feagan BG, Lichtenstein GR, et al.. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002, 4:1541-9. 10.1016\/S0140-6736(02)08512-4","journal-title":"Lancet"},{"key":"ref72","doi-asserted-by":"publisher","DOI":"10.5217\/ir.2019.09160","article-title":"Efficacy and safety of vedolizumab in Crohn's disease in patients from Asian countries in the GEMINI 2 study","volume":"19","author":"Banerjee R","year":"2021","unstructured":"Banerjee R, Chuah SW, Hilmi IN, et al.. Efficacy and safety of vedolizumab in Crohn's disease in patients from Asian countries in the GEMINI 2 study. Intest Res. 2021, 19:83-94. 10.5217\/ir.2019.09160","journal-title":"Intest Res"},{"key":"ref73","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602773","article-title":"Ustekinumab as induction and maintenance therapy for Crohn\u2019s disease","volume":"375","author":"Feagan BG","year":"2016","unstructured":"Feagan BG, Sandborn WJ, Gasink C, et al.. Ustekinumab as induction and maintenance therapy for Crohn\u2019s disease. N Engl J Med. 2016, 375:1946-60. 10.1056\/NEJMoa1602773","journal-title":"N Engl J Med"},{"key":"ref74","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2024.2316180","article-title":"Clinical use of biologics for Crohn's disease in adults: lessons learned from real-world studies","volume":"24","author":"Tursi A","year":"2024","unstructured":"Tursi A, Mocci G, Del Gaudio A, Papa A. Clinical use of biologics for Crohn's disease in adults: lessons learned from real-world studies. Expert Opin Biol Ther. 2024, 24:171-89. 10.1080\/14712598.2024.2316180","journal-title":"Expert Opin Biol Ther"},{"key":"ref75","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14030","article-title":"Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials","volume":"45","author":"Cholapranee A","year":"2017","unstructured":"Cholapranee A, Hazlewood GS, Kaplan GG, Peyrin-Biroulet L, Ananthakrishnan AN. Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials. Aliment Pharmacol Ther. 2017, 45:1291-302. 10.1111\/apt.14030","journal-title":"Aliment Pharmacol Ther"},{"key":"ref76","article-title":"Biologics Dose Escalation for the Treatment of Inflammatory Bowel Disease: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines","author":"Chao YS","year":"2018","unstructured":"Chao YS, Visintini S. Biologics Dose Escalation for the Treatment of Inflammatory Bowel Disease: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines. Canadian Agency for Drugs and Technologies in Health, Ottawa (ON); 2018."},{"key":"ref77","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2009.179994","article-title":"A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease","volume":"59","author":"Dotan I","year":"2010","unstructured":"Dotan I, Rachmilewitz D, Schreiber S, et al.. A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease. Gut. 2010, 59:760-6. 10.1136\/gut.2009.179994","journal-title":"Gut"},{"key":"ref78","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-14181-7_3","article-title":"Medical therapy for Crohn\u2019s disease: the present","author":"Fausel RA","year":"2015","unstructured":"Fausel RA, Zisman TL. Medical therapy for Crohn\u2019s disease: the present. Crohn\u2019s disease. Fichera A, Krane M (ed): Springer, Cham; 2015. 10.1007\/978-3-319-14181-7_3"},{"key":"ref79","doi-asserted-by":"publisher","DOI":"10.1055\/a-0903-2938","article-title":"Real-world biologic treatment and associated cost in patients with inflammatory bowel disease","volume":"57","author":"Brandes A","year":"2019","unstructured":"Brandes A, Groth A, Gottschalk F, et al.. Real-world biologic treatment and associated cost in patients with inflammatory bowel disease. Z Gastroenterol. 2019, 57:843-51. 10.1055\/a-0903-2938","journal-title":"Z Gastroenterol"},{"key":"ref80","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2011.239301.534","article-title":"A real life retrospective analysis of drug expenditure reveals no significant cost difference between infliximab and adalimumab in the treatment of adult Crohn\u2019s disease","volume":"60","author":"Lamb CA","year":"2011","unstructured":"Lamb CA, Price M, Robinson M, Gunn MC, Thompson NP, Mansfield JC. A real life retrospective analysis of drug expenditure reveals no significant cost difference between infliximab and adalimumab in the treatment of adult Crohn\u2019s disease. Gut. 2011, 60:251-52. 10.1136\/gut.2011.239301.534","journal-title":"Gut"},{"key":"ref81","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.16911","article-title":"Differential legal protections for Biologics vs small-molecule drugs in the US","volume":"332","author":"Wouters OJ","year":"2024","unstructured":"Wouters OJ, Vogel M, Feldman WB, Beall RF, Kesselheim AS, Tu SS. Differential legal protections for Biologics vs small-molecule drugs in the US. JAMA. 2024, 332:2101-8. 10.1001\/jama.2024.16911","journal-title":"JAMA"},{"key":"ref82","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109545","article-title":"Combination therapy in inflammatory bowel disease: current evidence and perspectives","volume":"114","author":"Dai C","year":"2023","unstructured":"Dai C, Huang YH, Jiang M. Combination therapy in inflammatory bowel disease: current evidence and perspectives. Int Immunopharmacol. 2023, 114:109545. 10.1016\/j.intimp.2022.109545","journal-title":"Int Immunopharmacol"},{"key":"ref83","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2021.03.034","article-title":"Dual biologic or small molecule therapy for treatment of inflammatory bowel disease: a systematic review and meta-analysis","volume":"20","author":"Ahmed W","year":"2022","unstructured":"Ahmed W, Galati J, Kumar A, et al.. Dual biologic or small molecule therapy for treatment of inflammatory bowel disease: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2022, 20:361-79. 10.1016\/j.cgh.2021.03.034","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref84","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904492","article-title":"Infliximab, azathioprine, or combination therapy for Crohn's disease","volume":"362","author":"Colombel JF","year":"2010","unstructured":"Colombel JF, Sandborn WJ, Reinisch W, et al.. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010, 362:1383-95. 10.1056\/NEJMoa0904492","journal-title":"N Engl J Med"},{"key":"ref85","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izx110","article-title":"Combining anti-TNF-\u03b1 and vedolizumab in the treatment of inflammatory bowel disease: a case series","volume":"24","author":"Buer LC","year":"2018","unstructured":"Buer LC, H\u00f8ivik ML, Warren DJ, Medhus AW, Moum BA. Combining anti-TNF-\u03b1 and vedolizumab in the treatment of inflammatory bowel disease: a case series. Inflamm Bowel Dis. 2018, 24:997-1004. 10.1093\/ibd\/izx110","journal-title":"Inflamm Bowel Dis"},{"key":"ref86","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-020-04563-0","article-title":"Surgery for inflammatory bowel disease in the era of biologics","volume":"24","author":"Lightner AL","year":"2020","unstructured":"Lightner AL. Surgery for inflammatory bowel disease in the era of biologics. J Gastrointest Surg. 2020, 24:1430-5. 10.1007\/s11605-020-04563-0","journal-title":"J Gastrointest Surg"},{"key":"ref87","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2008.01942.x","article-title":"Preoperative steroid use and risk of postoperative complications in patients with inflammatory bowel disease undergoing abdominal surgery","volume":"103","author":"Subramanian V","year":"2008","unstructured":"Subramanian V, Saxena S, Kang JY, Pollok RC. Preoperative steroid use and risk of postoperative complications in patients with inflammatory bowel disease undergoing abdominal surgery. Am J Gastroenterol. 2008, 103:2373-81. 10.1111\/j.1572-0241.2008.01942.x","journal-title":"Am J Gastroenterol"},{"key":"ref88","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.579","article-title":"The natural history of adult Crohn's disease in population-based cohorts","volume":"105","author":"Peyrin-Biroulet L","year":"2010","unstructured":"Peyrin-Biroulet L, Loftus EV Jr, Colombel JF, Sandborn WJ. The natural history of adult Crohn's disease in population-based cohorts. Am J Gastroenterol. 2010, 105:289-97. 10.1038\/ajg.2009.579","journal-title":"Am J Gastroenterol"},{"key":"ref89","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31711-1","article-title":"Crohn's disease","volume":"389","author":"Torres J","year":"2017","unstructured":"Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn's disease. Lancet. 2017, 389:1741-55. 10.1016\/S0140-6736(16)31711-1","journal-title":"Lancet"},{"key":"ref90","doi-asserted-by":"publisher","DOI":"10.1136\/gut.31.2.179","article-title":"Why do patients with ulcerative colitis relapse?","volume":"31","author":"Riley SA","year":"1990","unstructured":"Riley SA, Mani V, Goodman MJ, Lucas S. Why do patients with ulcerative colitis relapse?. Gut. 1990, 31:179-83. 10.1136\/gut.31.2.179","journal-title":"Gut"},{"key":"ref91","doi-asserted-by":"publisher","DOI":"10.1159\/000314230","article-title":"Therapy adherence in Crohn\u2019s disease: an adult case study","volume":"4","author":"Arai R","year":"2010","unstructured":"Arai R. Therapy adherence in Crohn\u2019s disease: an adult case study. Case Rep Gastroenterol. 2010, 4:153-7. 10.1159\/000314230","journal-title":"Case Rep Gastroenterol"},{"key":"ref92","doi-asserted-by":"publisher","DOI":"10.1016\/j.disamonth.2017.07.001","article-title":"A comprehensive review and update on Crohn's disease","volume":"64","author":"Gajendran M","year":"2018","unstructured":"Gajendran M, Loganathan P, Catinella AP, Hashash JG. A comprehensive review and update on Crohn's disease. Dis Mon. 2018, 64:20-57. 10.1016\/j.disamonth.2017.07.001","journal-title":"Dis Mon"},{"key":"ref93","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2022.2057582","article-title":"Factors associated with poor compliance amongst hospitalized, predominantly adolescent pediatric Crohn's disease patients","volume":"54","author":"Cohen NA","year":"2022","unstructured":"Cohen NA, Micic DM, Sakuraba A. Factors associated with poor compliance amongst hospitalized, predominantly adolescent pediatric Crohn's disease patients. Ann Med. 2022, 54:886-92. 10.1080\/07853890.2022.2057582","journal-title":"Ann Med"},{"key":"ref94","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-007-9968-0","article-title":"Medication non-adherence is associated with increased medical health care costs","volume":"53","author":"Kane S","year":"2008","unstructured":"Kane S, Shaya F. Medication non-adherence is associated with increased medical health care costs. Dig Dis Sci. 2008, 53:1020-4. 10.1007\/s10620-007-9968-0","journal-title":"Dig Dis Sci"},{"key":"ref95","doi-asserted-by":"publisher","DOI":"10.1159\/000341950","article-title":"Treatment of extraintestinal manifestations in inflammatory bowel disease","volume":"86","author":"Lakatos PL","year":"2012","unstructured":"Lakatos PL, Lakatos L, Kiss LS, Peyrin-Biroulet L, Schoepfer A, Vavricka S. Treatment of extraintestinal manifestations in inflammatory bowel disease. Digestion. 2012, 86:28-35. 10.1159\/000341950","journal-title":"Digestion"},{"key":"ref96","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-021-07025-y","article-title":"Patient perspectives and expectations in inflammatory bowel disease: a systematic review","volume":"67","author":"Al Khoury A","year":"2022","unstructured":"Al Khoury A, Balram B, Bessissow T, Afif W, Gonczi L, Abreu M, Lakatos PL. Patient perspectives and expectations in inflammatory bowel disease: a systematic review. Dig Dis Sci. 2022, 67:1956-74. 10.1007\/s10620-021-07025-y","journal-title":"Dig Dis Sci"},{"key":"ref97","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.07.022","article-title":"Lifetime economic burden of Crohn\u2019s disease and ulcerative colitis by age at diagnosis","volume":"18","author":"Lichtenstein GR","year":"2020","unstructured":"Lichtenstein GR, Shahabi A, Seabury SA, et al.. Lifetime economic burden of Crohn\u2019s disease and ulcerative colitis by age at diagnosis. Clin Gastroenterol Hepatol. 2020, 18:889-97. 10.1016\/j.cgh.2019.07.022","journal-title":"Clin Gastroenterol Hepatol"}],"container-title":["Cureus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cureus.com\/articles\/367814-a-comprehensive-review-of-the-role-of-biologics-and-small-molecule-therapies-in-the-long-term-management-of-crohns-disease","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T08:54:11Z","timestamp":1758531251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cureus.com\/articles\/367814-a-comprehensive-review-of-the-role-of-biologics-and-small-molecule-therapies-in-the-long-term-management-of-crohns-disease"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":97,"URL":"https:\/\/doi.org\/10.7759\/cureus.92901","relation":{},"ISSN":["2168-8184"],"issn-type":[{"value":"2168-8184","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9,22]]}}}