105
Views
0
CrossRef citations to date
0
Altmetric
REVIEW

Optimal Management of Refractory Crohn’s Disease: Current Landscape and Future Direction

ORCID Icon, ORCID Icon &
Pages 75-86 | Received 24 Jan 2024, Accepted 22 Mar 2024, Published online: 26 Mar 2024

References

  • Ouyang G, Pan G, Liu Q, et al. The global, regional, and national burden of pancreatitis in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. BMC Med. 2020;18(1):388. doi:10.1186/s12916-020-01859-5
  • Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18(1):56–66. doi:10.1038/s41575-020-00360-x
  • Faye AS, Colombel JF. Aging and IBD: a new challenge for clinicians and researchers. Inflamm Bowel Dis. 2022;28(1):126–132. doi:10.1093/ibd/izab039
  • Peery AF, Crockett SD, Murphy CC, et al. Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2018. Gastroenterology. 2019;156(1):254–272 e211. doi:10.1053/j.gastro.2018.08.063
  • Park KT, Ehrlich OG, Allen JI, et al. The cost of inflammatory bowel disease: an initiative from the Crohn’s & Colitis Foundation. Inflamm Bowel Dis. 2020;26(1):1–10. doi:10.1093/ibd/izz104
  • Knowles SR, Keefer L, Wilding H, Hewitt C, Graff LA, Mikocka-Walus A. Quality of life in inflammatory bowel disease: a systematic review and meta-analyses-part II. Inflamm Bowel Dis. 2018;24(5):966–976. doi:10.1093/ibd/izy015
  • Bharadwaj S, Fleshner P, Shen B. Therapeutic armamentarium for stricturing crohn’s disease: medical versus endoscopic versus surgical approaches. Inflamm Bowel Dis. 2015;21(9):2194–2213. doi:10.1097/MIB.0000000000000403
  • Shah SC, Colombel JF, Sands BE, Narula N. Systematic review with meta-analysis: mucosal healing is associated with improved long-term outcomes in Crohn’s disease. Aliment Pharmacol Ther. 2016;43(3):317–333. doi:10.1111/apt.13475
  • Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160(5):1570–1583. doi:10.1053/j.gastro.2020.12.031
  • Berg DR, Colombel JF, Ungaro R. The role of early biologic therapy in inflammatory bowel disease. Inflamm Bowel Dis. 2019;25(12):1896–1905. doi:10.1093/ibd/izz059
  • D’Haens G, Baert F, van Assche G, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet. 2008;371(9613):660–667. doi:10.1016/S0140-6736(08)60304-9
  • 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(1):52–65. doi:10.1053/j.gastro.2006.11.041
  • Kamm MA, Hanauer SB, Panaccione R, et al. Adalimumab sustains steroid-free remission after 3 years of therapy for Crohn’s disease. Aliment Pharmacol Ther. 2011;34(3):306–317. doi:10.1111/j.1365-2036.2011.04717.x
  • Colombel JF, Rutgeerts PJ, Sandborn WJ, et al. Adalimumab induces deep remission in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2014;12(3):414–422 e415. doi:10.1016/j.cgh.2013.06.019
  • Schreiber S, Colombel JF, Bloomfield R, et al. Increased response and remission rates in short-duration Crohn’s disease with subcutaneous certolizumab pegol: an analysis of PRECiSE 2 randomized maintenance trial data. Am J Gastroenterol. 2010;105(7):1574–1582. doi:10.1038/ajg.2010.78
  • Faleck DM, Winters A, Chablaney S, et al. Shorter disease duration is associated with higher rates of response to vedolizumab in patients with crohn’s disease but not ulcerative colitis. Clin Gastroenterol Hepatol. 2019;17(12):2497–2505 e2491. doi:10.1016/j.cgh.2018.12.040
  • 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(10340):2015–2030. doi:10.1016/S0140-6736(22)00467-6
  • Katz L, Gisbert JP, Manoogian B, et al. Doubling the infliximab dose versus halving the infusion intervals in Crohn’s disease patients with loss of response. Inflamm Bowel Dis. 2012;18(11):2026–2033. doi:10.1002/ibd.22902
  • Regueiro M, Siemanowski B, Kip KE, Plevy S. Infliximab dose intensification in Crohn’s disease. Inflamm Bowel Dis. 2007;13(9):1093–1099. doi:10.1002/ibd.20177
  • Chaparro M, Panes J, Garcia V, et al. Long-term durability of infliximab treatment in Crohn’s disease and efficacy of dose ”escalation” in patients losing response. J Clin Gastroenterol. 2011;45(2):113–118. doi:10.1097/MCG.0b013e3181ebaef9
  • Davidov Y, Ungar B, Bar-Yoseph H, et al. Association of induction infliximab levels with clinical response in perianal Crohn’s Disease. J Crohns Colitis. 2017;11(5):549–555. doi:10.1093/ecco-jcc/jjw182
  • Yarur AJ, Kanagala V, Stein DJ, et al. Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn’s disease. Aliment Pharmacol Ther. 2017;45(7):933–940. doi:10.1111/apt.13970
  • Faye AS, Lee KE, Hudesman D, Dervieux T. Older adults with inflammatory bowel disease are at higher risk of developing antibodies to infliximab. Inflamm Bowel Dis. 2024. doi:10.1093/ibd/izad305
  • Singh S, Stitt LW, Zou G, et al. Early combined immunosuppression may be effective and safe in older patients with Crohn’s disease: post hoc analysis of REACT. Aliment Pharmacol Ther. 2019;49(9):1188–1194. doi:10.1111/apt.15214
  • Meserve J, Ma C, Dulai PS, Jairath V, Singh S. Effectiveness of reinduction and/or dose escalation of ustekinumab in Crohn’s Disease: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2022;20(12):2728–2740 e2721. doi:10.1016/j.cgh.2021.10.002
  • Patel D, Martin S, Luo M, et al. Real-world effectiveness of vedolizumab dose escalation in patients with inflammatory bowel disease: a systematic literature review. Crohns Colitis. 2022;4(3):otac020. doi:10.1093/crocol/otac020
  • Panaccione R, Long M, Ran Z, et al. S805 Efficacy of upadacitinib dose escalation in a phase 3 long-term extension ulcerative colitis study. Am J Gastroenterol. 2022;117(10S):e574–e575. doi:10.14309/01.ajg.0000859860.18839.f9
  • Sandborn W, Panes J, Peyrin-Biroulet L, et al. DOP79 Dose escalation of upadacitinib in Crohn’s disease patients with an inadequate response: data from the randomised CELEST study. J Crohns Colitis. 2020;14(14):S117–S118. doi:10.1093/ecco-jcc/jjz203.118
  • Sandborn WJ, Ferrante M, Bhandari BR, et al. Efficacy and safety of continued treatment with mirikizumab in a phase 2 trial of patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2022;20(1):105–115 e114. doi:10.1016/j.cgh.2020.09.028
  • Rendon A, Schakel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20(6). doi:10.3390/ijms20061475
  • Pugliese D, Daperno M, Fiorino G, et al. Real-life effectiveness of ustekinumab in inflammatory bowel disease patients with concomitant psoriasis or psoriatic arthritis: an IG-IBD study. Dig Liver Dis. 2019;51(7):972–977. doi:10.1016/j.dld.2019.03.007
  • Fradkov E, Sheehan J, Cushing K, Higgins PDR. Efficacy of ustekinumab in Crohn’s Disease with and without concurrent autoimmune skin disease. Inflamm Bowel Dis. 2022;28(6):895–904. doi:10.1093/ibd/izab201
  • Papp KA, Blauvelt A, Bukhalo M, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017;376(16):1551–1560. doi:10.1056/NEJMoa1607017
  • Xie W, Xiao S, Huang H, Zhang Z. Incidence of and risk factors for paradoxical psoriasis or psoriasiform lesions in inflammatory bowel disease patients receiving Anti-TNF therapy: systematic review with meta-analysis. Front Immunol. 2022;13:847160. doi:10.3389/fimmu.2022.847160
  • Toussirot E. The use of janus kinase inhibitors in axial spondyloarthritis: current insights. Pharmaceuticals. 2022;15(3):270. doi:10.3390/ph15030270
  • Ramiro S, Nikiphorou E, Sepriano A, et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis. 2023;82(1):19–34. doi:10.1136/ard-2022-223296
  • Vernero M, Astegiano M, Ribaldone DG. New onset of inflammatory bowel disease in three patients undergoing IL-17A inhibitor secukinumab: a case series. Am J Gastroenterol. 2019;114(1):179–180. doi:10.1038/s41395-018-0422-z
  • Sands BE, Irving PM, Hoops T, et al. Ustekinumab versus Adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn’s disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial. Lancet. 2022;399(10342):2200–2211.
  • Peyrin-Biroulet L, Chapman C, Colombel JF, et al. S1 risankizumab versus ustekinumab in patients with moderate to severe Crohn’s Disease: results from the phase 3B SEQUENCE Trial. Am J Gastroenterol. 2023;118(12S):S1. doi:10.14309/01.ajg.0000995740.88073.c5
  • Singh S, Murad MH, Fumery M, et al. Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn’s disease: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(12):1002–1014. doi:10.1016/S2468-1253(21)00312-5
  • Feagan B, Sands BE, Siegel CA, et al. DOP87 the anti-TL1A antibody PRA023 demonstrated proof-of-concept in Crohn’s Disease: phase 2a APOLLO-CD Study Results. J Crohns Colitis. 2023;17(Supplement_1):i162–i164. doi:10.1093/ecco-jcc/jjac190.0127
  • Sands BE, Peyrin-Biroulet L, Danese S, et al. OP40 PRA023 demonstrated efficacy and favorable safety as induction therapy for moderately to severely active UC: phase 2 ARTEMIS-UC study results. J Crohns Colitis. 2023;17(Supplement_1):i56–i59. doi:10.1093/ecco-jcc/jjac190.0040
  • Torres J, Boyapati RK, Kennedy NA, Louis E, Colombel JF, Satsangi J. Systematic review of effects of withdrawal of immunomodulators or biologic agents from patients with inflammatory bowel disease. Gastroenterology. 2015;149(7):1716–1730. doi:10.1053/j.gastro.2015.08.055
  • Reenaers C, Mary JY, Nachury M, et al. Outcomes 7 years after infliximab withdrawal for patients with Crohn’s Disease in sustained remission. Clin Gastroenterol Hepatol. 2018;16(2):234–243 e232. doi:10.1016/j.cgh.2017.09.061
  • Louis E, Resche-Rigon M, Laharie D, et al. Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn’s disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023;8(3):215–227.
  • Raine T, Danese S. Breaking through the therapeutic ceiling: what will it take? Gastroenterology. 2022;162(5):1507–1511. doi:10.1053/j.gastro.2021.09.078
  • McCormack MD, Wahedna NA, Aldulaimi D, Hawker P. Emerging role of dual biologic therapy for the treatment of inflammatory bowel disease. World J Clin Cases. 2023;11(12):2621–2630. doi:10.12998/wjcc.v11.i12.2621
  • Alayo QA, Fenster M, Altayar O, et al. Systematic review with meta-analysis: safety and effectiveness of combining biologics and small molecules in inflammatory bowel disease. Crohns Colitis. 2022;4(1):otac002. doi:10.1093/crocol/otac002
  • Feagan BG, Sands BE, Sandborn WJ, et al. Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial. Lancet Gastroenterol Hepatol. 2023;8(4):307–320. doi:10.1016/S2468-1253(22)00427-7
  • Colombel JF, Ungaro RC, Sands BE, et al. Vedolizumab, adalimumab, and methotrexate combination therapy in crohn’s disease (EXPLORER). Clin Gastroenterol Hepatol. 2023. doi:10.1016/j.cgh.2023.09.010
  • Cheong J, Faye A, Shaukat A. Colorectal cancer screening and surveillance in the geriatric population. Curr Gastroenterol Rep. 2023;25(7):141–145.
  • Lo CH, Lochhead P, Khalili H, et al. Dietary inflammatory potential and risk of crohn’s disease and ulcerative colitis. Gastroenterology. 2020;159(3):873–883 e871. doi:10.1053/j.gastro.2020.05.011
  • Jaber M, Altamimi M, Altamimi A, Cavaliere S, De Filippis F. Mediterranean diet diminishes the effects of Crohn’s disease and improves its parameters: a systematic review. Nutr Health. 2022;2601060221102281. doi:10.1177/02601060221102281
  • Lewis JD, Sandler RS, Brotherton C, et al. A randomized trial comparing the specific carbohydrate diet to a Mediterranean diet in adults with Crohn’s Disease. Gastroenterology. 2021;161(3):837–852 e839. doi:10.1053/j.gastro.2021.05.047
  • Levine A, Wine E, Assa A, et al. Crohn’s Disease exclusion diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial. Gastroenterology. 2019;157(2):440–450 e448. doi:10.1053/j.gastro.2019.04.021
  • Yanai H, Levine A, Hirsch A, et al. The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022;7(1):49–59. doi:10.1016/S2468-1253(21)00299-5
  • Feng J, Chen Y, Liu Y, et al. Efficacy and safety of fecal microbiota transplantation in the treatment of ulcerative colitis: a systematic review and meta-analysis. Sci Rep. 2023;13(1):14494. doi:10.1038/s41598-023-41182-6
  • Sokol H, Landman C, Seksik P, et al. Fecal microbiota transplantation to maintain remission in Crohn’s disease: a pilot randomized controlled study. Microbiome. 2020;8(1):12. doi:10.1186/s40168-020-0792-5
  • Fehily SR, Basnayake C, Wright EK, Kamm MA. Fecal microbiota transplantation therapy in Crohn’s disease: systematic review. J Gastroenterol Hepatol. 2021;36(10):2672–2686. doi:10.1111/jgh.15598
  • Leach ST, Mitchell HM, Eng WR, Zhang L, Day AS. Sustained modulation of intestinal bacteria by exclusive enteral nutrition used to treat children with Crohn’s disease. Aliment Pharmacol Ther. 2008;28(6):724–733. doi:10.1111/j.1365-2036.2008.03796.x
  • Fernández-Banares F, Cabré E, Esteve-Comas M, Gassull MA. How effective is enteral nutrition in inducing clinical remission in active Crohn’s disease? A meta-analysis of the randomized clinical trials. JPEN J Parenter Enteral Nutr. 1995;19(5):356–364. doi:10.1177/0148607195019005356
  • Griffiths AM, Ohlsson A, Sherman PM, Sutherland LR. Meta-analysis of enteral nutrition as a primary treatment of active Crohn’s disease. Gastroenterology. 1995;108(4):1056–1067. doi:10.1016/0016-5085(95)90203-1
  • Narula N, Dhillon A, Zhang D, Sherlock ME, Tondeur M, Zachos M. Enteral nutritional therapy for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2018;4(4):Cd000542. doi:10.1002/14651858.CD000542.pub3
  • Breton J, Kastl A, Conrad MA, Baldassano RN. Positioning biologic therapies in the management of pediatric inflammatory bowel disease. Gastroenterol Hepatol. 2020;16(8):400–414.
  • Walters TD, Kim MO, Denson LA, et al. Increased effectiveness of early therapy with anti-tumor necrosis factor-alpha vs an immunomodulator in children with Crohn’s disease. Gastroenterology. 2014;146(2):383–391. doi:10.1053/j.gastro.2013.10.027
  • Kang B, Choe YH. Early biologic treatment in pediatric Crohn’s Disease: catching the therapeutic window of opportunity in early disease by treat-to-target. Pediatr Gastroenterol Hepatol Nutr. 2018;21(1):1–11. doi:10.5223/pghn.2018.21.1.1
  • Ouahed J, Spencer E, Kotlarz D, et al. Very early onset inflammatory bowel disease: a clinical approach with a focus on the role of genetics and underlying immune deficiencies. Inflamm Bowel Dis. 2020;26(6):820–842. doi:10.1093/ibd/izz259
  • Alós R, Hinojosa J. Timing of surgery in Crohn’s disease: a key issue in the management. World J Gastroenterol. 2008;14(36):5532–5539. doi:10.3748/wjg.14.5532
  • Stevens TW, Haasnoot ML, D’Haens GR, et al. Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn’s disease: retrospective long-term follow-up of the LIR!C trial. Lancet Gastroenterol Hepatol. 2020;5(10):900–907. doi:10.1016/S2468-1253(20)30117-5
  • Agrawal M, Ebert AC, Poulsen G, et al. Early ileocecal resection for crohn’s disease is associated with improved long-term outcomes compared with anti-tumor necrosis factor therapy: a population-based cohort study. Gastroenterology. 2023;165(4):976–985 e973. doi:10.1053/j.gastro.2023.05.051
  • Fernandez C, Gajic Z, Esen E, et al. Preoperative risk factors for adverse events in adults undergoing bowel resection for inflammatory bowel disease: 15-year assessment of the American college of surgeons national surgical quality improvement program. Am J Gastroenterol. 2023;118(12):2230–2241. doi:10.14309/ajg.0000000000002395
  • Rutgeerts P. Review article: treatment of perianal fistulizing Crohn’s disease. Aliment Pharmacol Ther. 2004;20(Suppl 4):106–110. doi:10.1111/j.1365-2036.2004.02060.x
  • Lansdorp CA, Gecse KB, Buskens CJ, et al. Hyperbaric oxygen therapy for the treatment of perianal fistulas in 20 patients with Crohn’s disease. Aliment Pharmacol Ther. 2021;53(5):587–597.
  • Feitosa MR, Parra RS, Machado VF, et al. Adjunctive hyperbaric oxygen therapy in refractory Crohn’s Disease: an observational study. Gastroenterol Res Pract. 2021;2021:6628142. doi:10.1155/2021/6628142
  • Cao Y, Su Q, Zhang B, Shen F, Li S. Efficacy of stem cells therapy for Crohn’s fistula: a meta-analysis and systematic review. Stem Cell Res Ther. 2021;12(1):32. doi:10.1186/s13287-020-02095-7
  • Panés J, García-Olmo D, Van Assche G, et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016;388(10051):1281–1290. doi:10.1016/S0140-6736(16)31203-X
  • Adamina M, Bonovas S, Raine T, et al. ECCO guidelines on therapeutics in Crohn’s Disease: surgical treatment. J Crohns Colitis. 2020;14(2):155–168. doi:10.1093/ecco-jcc/jjz187
  • Alexander T, Greco R. Hematopoietic stem cell transplantation and cellular therapies for autoimmune diseases: overview and future considerations from the Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2022;57(7):1055–1062. doi:10.1038/s41409-022-01702-w
  • Lopez-Cubero SO, Sullivan KM, McDonald GB. Course of Crohn’s disease after allogeneic marrow transplantation. Gastroenterology. 1998;114(3):433–440. doi:10.1016/S0016-5085(98)70525-6
  • Wang R, Yao Q, Chen W, et al. Stem cell therapy for Crohn’s disease: systematic review and meta-analysis of preclinical and clinical studies. Stem Cell Res Ther. 2021;12(1):463. doi:10.1186/s13287-021-02533-0
  • Guisado D, Talware S, Singh S, et al. Reprogramming of the intestinal immune cell compartment defines the response to autologous stem cell transplantation in Crohn’s Disease. Inflamm Bowel Dis. 2023;29(Supplement_1):S51–S52. doi:10.1093/ibd/izac247.101
  • Wrighton KH. Malassezia restricta plays CARDs in the gut. Nat Rev Microbiol. 2019;17(5):266–267. doi:10.1038/s41579-019-0188-3
  • Fornaro R, Actis GC, Caviglia GP, Pitoni D, Ribaldone DG. Inflammatory bowel disease: role of vagus nerve stimulation. J Clin Med. 2022;11(19):5690. doi:10.3390/jcm11195690