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Practical Approaches to “Top–Down” Therapies for Crohn’s Disease

  • Inflammatory Bowel Disease (S Hanauer, Section Editor)
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Abstract

Crohn’s disease (CD) is a chronic, progressive, and disabling disease that leads in most cases to the development of bowel damage presenting as a fistula, abscess, or stricture. For years, therapy for Crohn’s disease has been based on a “step-up” approach, in which anti-TNF agents are administered after the failure of steroids and immunosuppressants. However, recent studies have suggested that early introduction of anti-TNF agents combined with immunosuppressants can modify the natural history of the disease. Patients who could benefit more of this “top–down” strategy would be those at elevated risk of a complicated or severe inflammatory bowel disease or with factors that can predict an aggressive disease course. Therefore, the management of a patient with CD should be personalized, taking into account the patient’s specific characteristics and comorbidities, disease activity, site and behavior of the disease, and predictable factors of poor prognosis. A balance between medication and potential adverse effects should be achieved, trying to avoid under or overtreatment, always discussing the different therapeutic options with the patient. The natural history of ulcerative colitis differs from CD and, to date, there is not much scientific evidence on the use of early combined immunosuppression.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Van Assche G, Dignass A, Panes J, Beaugerie L, Karagiannis J, Allez M, 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.

    Article  PubMed  Google Scholar 

  2. Louis E, Collard A, Oger AF, Degroote E, Aboul Nasr El Yafi FA, Belaiche J. Behaviour of Crohn’s disease according to the Vienna classification: changing pattern over the course of the disease. Gut. 2001;49:777–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Henriksen M, Jahnsen J, Lygren I, Aadland E, Schulz T, Vatn MH, et al. Clinical course in Crohn’s disease: results of a five-year population-based follow-up study (the IBSEN study). Scand J Gastroenterol. 2007;42:602–10.

    Article  PubMed  Google Scholar 

  4. Cosnes J, Cattan S, Blain A, Beaugerie L, Carbonnel F, Parc R, et al. Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis. 2002;8:244–50.

    Article  PubMed  Google Scholar 

  5. Dignass A, Lindsay JO, Sturm A, Windsor A, Colombel JF, Allez M, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: current management. J Crohn's Colitis. 2012;6:991–1030.

    Article  Google Scholar 

  6. Dignass A, Van Assche G, Lindsay JO, Lemann M, Soderholm J, Colombel JF, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: current management. J Crohn's Colitis. 2010;4:28–62.

    Article  CAS  Google Scholar 

  7. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–9.

    Article  CAS  PubMed  Google Scholar 

  8. Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, Macintosh D, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006;130:323–32.

    Article  CAS  PubMed  Google Scholar 

  9. Sandborn WJ, Hanauer SB, Rutgeerts P, Fedorak RN, Lukas M, Macintosh DG, et al. Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut. 2007;56:1232–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sandborn WJ, Van Assche G, Reinisch W, Colombel J, D’Haens G, Wolf DC, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:257–65.

    Article  CAS  PubMed  Google Scholar 

  11. 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;146:85–95.

    Article  CAS  PubMed  Google Scholar 

  12. Frolkis AD, Dykeman J, Negrón ME, Debruyn J, Jette N, Fiest KM, et al. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. Gastroenterology. 2013;145:996–1006.

    Article  PubMed  Google Scholar 

  13. Dignass A, Eliakim R, Magro F, Maaser C, Chowers Y, Geboes K, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. J Crohn's Colitis. 2012;6:965–90.

    Article  Google Scholar 

  14. Peyrin-Biroulet L, Reinisch W, Colombel JF, Mantzaris GJ, Kornbluth A, Diamond R, et al. Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn’s disease in the SONIC trial. Gut. 2014;63:88–95.

    Article  PubMed  Google Scholar 

  15. Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, Bryant RV, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110:1324–38.

    Article  CAS  PubMed  Google Scholar 

  16. Best WR, Becktel JM, Singleton JW, Kern F. Development of a Crohn’s disease activity index. National cooperative Crohn's disease study. Gastroenterology. 1976;70:439–44.

    CAS  PubMed  Google Scholar 

  17. Louis E, Michel V, Hugot JP, Reenaers C, Fontaine F, Delforge M, et al. Early development of stricturing or penetrating pattern in Crohn’s disease is influenced by disease location, number of flares, and smoking but not by NOD2/CARD15 genotype. Gut. 2003;52:552–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lakatos PL, Czegledi Z, Szamosi T, Banai J, David G, Zsigmond F, et al. Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn’s disease. World J Gastroenterol. 2009;15:3504–10.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Romberg-Camps MJ, Dagnelie PC, Kester AD, Hesselink-Van De Kruijs MA, Cilissen M, Engels LG, et al. Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease. Am J Gastroenterol. 2009;104:371–83.

    Article  CAS  PubMed  Google Scholar 

  20. Wolters FL, Russel MG, Sijbrandij J, Ambergen T, Odes S, Riis L, et al. Phenotype at diagnosis predicts recurrence rates in Crohn’s disease. Gut. 2006;55:1124–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chow DK, Sung JJ, Wu JC, Tsoi KK, Leong RW, Chan FK. Upper gastrointestinal tract phenotype of Crohn’s disease is associated with early surgery and further hospitalization. Inflamm Bowel Dis. 2009;15:551–7.

    Article  PubMed  Google Scholar 

  22. Beaugerie L, Seksik P, Nion-Larmurier I, Gendre JP, Cosnes J. Predictors of Crohn’s disease. Gastroenterology. 2006;130:650–6.

    Article  PubMed  Google Scholar 

  23. Loly C, Belaiche J, Louis E. Predictors of severe Crohn’s disease. Scand J Gastroenterol. 2008;43:948–54.

    Article  CAS  PubMed  Google Scholar 

  24. Allez M, Lemann M, Bonnet J, Cattan P, Jian R, Modigliani R. Long term outcome of patients with active Crohn’s disease exhibiting extensive and deep ulcerations at colonoscopy. Am J Gastroenterol. 2002;97:947–53.

    PubMed  Google Scholar 

  25. Cosnes J, Bourrier A, Laharie D, Nahon S, Bouhnik Y, Carbonnel F, et al. Early administration of azathioprine vs conventional management of Crohn’s Disease: a randomized controlled trial. Gastroenterology. 2013;145:755–8. In the RAPID trial, the efficacy of early treatment with azathioprine (within 6 months after diagnosis) was compared with the conventional management in CD patients at high risk for disabling disease. It was observed that early administration of azathioprine was no more effective than conventional management of CD in increasing time of clinical remission.

    Article  Google Scholar 

  26. Panes J, Lopez-Sanroman A, Bermejo F, Garcia-Sanchez V, Esteve M, Torres Y, et al. Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn’s disease. Gastroenterology. 2013;145:766–74. In the AZTEC study, patients with recent diagnosis of CD were randomly assigned to azathioprine versus placebo. The rates of relapse and corticoisteroid-free remission were similar in both groups.

    Article  CAS  PubMed  Google Scholar 

  27. Sands BE, Blank MA, Diamond RH, Barrett JP, Van Deventer SJ. Maintenance infliximab does not result in increased abscess development in fistulizing Crohn’s disease: results from the ACCENT II study. Aliment Pharmacol Ther. 2006;23:1127–36.

    Article  CAS  PubMed  Google Scholar 

  28. D’Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet. 2008;371:660–7.

    Article  PubMed  Google Scholar 

  29. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–95.

    Article  CAS  PubMed  Google Scholar 

  30. 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’s disease: the CHARM trial. Gastroenterology. 2007;132:52–65.

    Article  CAS  PubMed  Google Scholar 

  31. Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OØ, Hanauer SB, Mccolm J, et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007;357:239–50.

    Article  CAS  PubMed  Google Scholar 

  32. Khanna R, Bressler B, Levesque BG, Zou G, Stitt LW, Greenberg GR, et al. Early combined immunosuppression for the management of Crohn’s disease (REACT): a cluster randomised controlled trial. Lancet. 2015;386:1825–34. Early combined immunosuppression with adalimumab and IMM versus conventional treatment was analyzed in patients with long-established CD in community gastroenterology practices. The benefits of the early combined immunosuppression for clinical remission were not significantly better than those of conventional treatment, but patients under combined therapy presented a reduction in surgery, hospitalization rate or serious disease-related complications.

    Article  PubMed  Google Scholar 

  33. Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Price S, et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT™ registry. Am J Gastroenterol. 2012;107:1409–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Annese V, Beaugerie L, Egan L, Biancone L, Bolling C, Brandts C, et al. European evidence-based consensus: inflammatory bowel disease and malignancies. J Crohn’s Colitis. 2015;9:945–65. Global prevalence of cancer is increasing. This is the first European guideline describing the impact of IBD on malignancy. It comprises a set of consesus statements on optimal risk/benefit strategies for treating IBD patients with cancer or a history of cancer.

    Article  Google Scholar 

  35. Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Langholff W, et al. Drug therapies and the risk of malignancy in Crohn’s disease: results from the TREAT™ registry. Am J Gastroenterol. 2014;109:212–23.

    Article  CAS  PubMed  Google Scholar 

  36. Beaugerie L, Brousse N, Bouvier AM, Colombel JF, Lémann M, Cosnes J, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet. 2009;374:1617–25.

    Article  CAS  PubMed  Google Scholar 

  37. Lichtenstein GR, Rutgeerts P, Sandborn WJ, Sands BE, Diamond RH, Blank M, et al. A pooled analysis of infections, malignancy, and mortality in Infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease. Am J Gastroenterol. 2012;107:1051–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Williams CJ, Peyrin-Biroulet L, Ford AC. Systematic review with meta-analysis: malignancies with anti-tumour necrosis factor-α therapy in inflammatory bowel disease. Aliment Pharmacol Ther. 2014;39:447–58.

    Article  CAS  PubMed  Google Scholar 

  39. Nyboe Andersen N, Pasternak B, Basit S, Andersson M, Svanström H, Caspersen S, et al. Association between tumor necrosis factor-α antagonists and risk of cancer in patients with inflammatory bowel disease. JAMA. 2014;311:2406–13.

    Article  PubMed  Google Scholar 

  40. Peyrin-Biroulet L, Deltenre P, de Suray N, Branche J, Sandborn WJ, Colombel JF. Efficacy and safety of tumor necrosis factor antagonists in Crohn’s disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol. 2008;6:644–53.

    Article  CAS  PubMed  Google Scholar 

  41. Deepak P, Sifuentes H, Sherid M, Stobaugh D, Sadozai Y, Ehrenpreis ED. T-cell non-Hodgkin’s lymphomas reported to the FDA AERS with tumor necrosis factor-alpha (TNF-α) inhibitors: results of the REFURBISH study. Am J Gastroenterol. 2013;108:99–105.

    Article  CAS  PubMed  Google Scholar 

  42. Kotlyar DS, Osterman MT, Diamond RH, Porter D, Blonski WC, Wasik M, et al. A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2011;9:36–41.

    Article  CAS  PubMed  Google Scholar 

  43. Beaugerie L, Carrat F, Colombel JF, Bouvier AM, Sokol H, Babouri A, et al. Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer. Gut. 2014;63:1416–23.

    Article  PubMed  Google Scholar 

  44. Magro F, Peyrin-Biroulet L, Sokol H, Aldeger X, Costa A, Higgins PD, et al. Extra-intestinal malignancies in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (III). J Crohn's Colitis. 2014;8:31–44.

    Article  Google Scholar 

  45. Peyrin-Biroulet L, Khosrotehrani K, Carrat F, Bouvier AM, Chevaux JB, Simon T, et al. Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease. Gastroenterology. 2011;141:1621–8.

    Article  CAS  PubMed  Google Scholar 

  46. Ariyaratnam J, Subramanian V. Association between thiopurine use and nonmelanoma skin cancers in patients with inflammatory bowel disease: a meta-analysis. Am J Gastroenterol. 2014;109:163–9.

    Article  CAS  PubMed  Google Scholar 

  47. Singh H, Nugent Z, Demers AA, Bernstein CN. Increased risk of nonmelanoma skin cancers among individuals with inflammatory bowel disease. Gastroenterology. 2011;141:1612–20.

    Article  PubMed  Google Scholar 

  48. Long MD, Martin CF, Pipkin CA, Herfarth HH, Sandler RS, Kappelman MD. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143:390–9.

    Article  PubMed  PubMed Central  Google Scholar 

  49. McKenna MR, Stobaugh DJ, Deepak P. Melanoma and non-melanoma skin cancer in inflammatory bowel disease patients following tumor necrosis factor inhibitor monotherapy and in combination with thiopurines: analysis of the food and drug administration adverse event reporting system. J Gastrointestin Liver Dis. 2014;23:267–71.

    PubMed  Google Scholar 

  50. Singh S, Nagpal SJ, Murad MH, Yadav S, Kane SV, Pardi DS, et al. Inflammatory bowel disease is associated with an increased risk of melanoma: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2014;12:210–8.

    Article  PubMed  Google Scholar 

  51. Allegretti JR, Barnes EL, Cameron A. Are patients with inflammatory bowel disease on chronic immunosuppressive therapy at increased risk of cervical high-grade dysplasia/cancer? A meta-analysis. Inflamm Bowel Dis. 2015;21:1089–97.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Katsanos KH, Roda G, Brygo A, Delaporte E, Colombel JF. Oral cancer and oral precancerous lesions in inflammatory bowel diseases: a systematic review. J Crohn's Colitis. 2015;9:1043–52.

    Article  Google Scholar 

  53. Van der Valk ME, Mangen MJ, Leenders M, Dijkstra G, van Bodegraven AA, Fidder HH, et al. Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFα therapy: results from the COIN study. Gut. 2014;63:72–9.

    Article  PubMed  Google Scholar 

  54. Chaparro M, Ordás I, Cabré E, Garcia-Sanchez V, Bastida G, Peñalva M, et al. Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients. Inflamm Bowel Dis. 2013;19:1404–10.

    Article  PubMed  Google Scholar 

  55. Wang F, Lin X, Zhao Q, Li J. Adverse symptoms with anti-TNF-alpha therapy in inflammatory bowel disease: systematic review and duration-response meta-analysis. Eur J Clin Pharmacol. 2015;71:911–9.

    Article  CAS  PubMed  Google Scholar 

  56. Bouhnik Y, Lemann M, Mary JY, Scemama G, Taï R, Matuchansky C, et al. Long-term follow-up of patients with Crohn’s disease treated with azathioprine or 6-mercaptopurine. Lancet. 1996;347:215–9.

    Article  CAS  PubMed  Google Scholar 

  57. Lémann M, Mary JY, Colombel JF, Duclos B, Soule JC, Lerebours E, et al. A randomized, double-blind, controlled withdrawal trial in Crohn’s disease patients in long-term remission on azathioprine. Gastroenterology. 2005;128:1812–8.

    Article  PubMed  Google Scholar 

  58. Van Assche G, Magdelaine-Beuzelin C, D’Haens G, Baert F, Noman M, Vermeire S, et al. Withdrawal of immunosuppression in Crohn’s disease treated with scheduled infliximab maintenance: a randomized trial. Gastroenterology. 2008;134:1861–8.

    Article  PubMed  Google Scholar 

  59. Drobne D, Bossuyt P, Breynaert C, Cattaert T, Vande Casteele N, Compernolle G, et al. Withdrawal of immunomodulators after co-treatment does not reduce trough level of infliximab in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2015;13:514–21.

    Article  CAS  PubMed  Google Scholar 

  60. Louis E, Mary JY, Vernier-Massouille G, Grimaud JC, Bouhnik Y, Laharie D, et al. Maintenance of remission among patients with Crohn’s disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology. 2012;142:63–70.

    Article  CAS  PubMed  Google Scholar 

  61. Waugh AW, Garg S, Matic K, Gramlich L, Wong C, Sadowski DC, et al. Maintenance of clinical benefit in Crohn’s disease patients after discontinuation of infliximab: long-term follow-up of a single centre cohort. Aliment Pharmacol Ther. 2010;32:1129–34.

    Article  CAS  PubMed  Google Scholar 

  62. Steenholdt C, Molazahi A, Ainsworth MA, Brynskov J, Thomsen OØ, Seidelin JB. Outcome after discontinuation of infliximab in patients with inflammatory bowel disease in clinical remission: an observational Danish single center study. Scand J Gastroenterol. 2012;47:518–27.

    Article  CAS  PubMed  Google Scholar 

  63. Molnár T, Lakatos PL, Farkas K, Nagy F, Szepes Z, Miheller P, et al. Predictors of relapse in patients with Crohn’s disease in remission after 1 year of biological therapy. Aliment Pharmacol Ther. 2013;37:225–33.

    Article  PubMed  Google Scholar 

  64. Rismo R, Olsen T, Cui G, Paulssen EJ, Christiansen I, Johnsen K, et al. Normalization of mucosal cytokine gene expression levels predicts long-term remission after discontinuation of anti-TNF therapy in Crohn’s disease. Scand J Gastroenterol. 2013;48:311–9.

    Article  CAS  PubMed  Google Scholar 

  65. Molander P, Färkkilä M, Salminen K, Kemppainen H, Blomster T, Koskela R, et al. Outcome after discontinuation of TNFα-blocking therapy in patients with inflammatory bowel disease in deep remission. Inflamm Bowel Dis. 2014;20:1021–8.

    PubMed  Google Scholar 

  66. Brooks AJ, Sebastian S, Cross SS, Robinson K, Warren L, Wright A, et al. Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn’s disease in established remission. J Crohns Colitis. 2015. doi:10.1016/j.crohns.2014.09.007.

  67. Chauvin A, Le Thuaut A, Belhassan M, Le Baleur Y, Mesli F, Bastuji-Garin S, et al. Infliximab as a bridge to remission maintained by antimetabolite therapy in Crohn’s disease: a retrospective study. Dig Liver Dis. 2014;46:695–700.

    Article  CAS  PubMed  Google Scholar 

  68. Gisbert JP, Marín AC, Chaparro M. Systematic review: factors associated with relapse of inflammatory bowel disease after discontinuation of anti-TNF therapy. Aliment Pharmacol Ther. 2015;42:391–405. The overall risk of relapse after discontinuation of anti-TNF therapy was 44 % for Crohn’s disease and 38 % for ulcerative colitis. Factors associated with a higher risk of relapse were younger age, smoking, longer disease duration, and fistulizing perianal CD. Laboratory markers such as low hemoglobin levels, high C-reactive protein levels and high fecal calprotectin seemed to increase the risk of relapse. On the other hand, low serum anti-TNF levels seem to be associated with a lower risk of flare-up. Mucosal healing seems to decrease the risk of relapse after anti-TNF therapy discontinuation. Re-administration of the drug in those who relapsed after stop** treatment was effective and safe.

    Article  CAS  PubMed  Google Scholar 

  69. Gisbert JP, Marín AC, Chaparro M. The risk of relapse after anti-TNF discontinuation in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2016. doi:10.1038/ajg.2016.54.

  70. Sandborn WJ, Colombel JF, Enns R, Feagan BG, Hanauer SB, Lawrance IC, et al. Natalizumab induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2005;353:1912–25.

    Article  CAS  PubMed  Google Scholar 

  71. Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369:711–21.

    Article  CAS  PubMed  Google Scholar 

  72. Sandborn WJ, Gasink C, Gao LL, Blank MA, Johanns J, Guzzo C, et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med. 2012;367:1519–28.

    Article  CAS  PubMed  Google Scholar 

  73. 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's disease. Clin Gastroenterol Hepatol. 2014;1485–93.

  74. Monteleone G, Neurath MF, Ardizzone S, Di Sabatino A, Fantini MC, Castiglione F, et al. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn’s disease. N Engl J Med. 2015;372:1104–13.

    Article  CAS  PubMed  Google Scholar 

  75. Dai C, Liu WX, Jiang M, Sun MJ. Mucosal healing did not predict sustained clinical remission in patients with IBD after discontinuation of one-year infliximab therapy. PLoS One. 2014;9, e110797.

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Department of Gastroenterology and Hepatology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

    Aranzazu Jauregui Amezaga & Gert Van Assche

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Correspondence to Aranzazu Jauregui Amezaga.

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AJA declares that she has no conflicts of interest. GVA reports consultancy for Zealand Pharma, Shire, Abbott, Novartis, MSD, Janssen, BMS, Fering, Chiesi, and Takeda; grants from MSD, Abbott, and Zealand Pharma; and payment for lectures from Janssen, Abbott, Ferring, Aptalis, and MSD, outside the submitted work.

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Amezaga, A.J., Van Assche, G. Practical Approaches to “Top–Down” Therapies for Crohn’s Disease. Curr Gastroenterol Rep 18, 35 (2016). https://doi.org/10.1007/s11894-016-0507-z

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