Treatment of Crohn’s disease of inflammatory, stenotic, and fistulizing phenotypes

  • Marla C. Dubinsky
  • Phillip P. Fleshner

Opinion statement

The heterogeneous nature of Crohn’s disease (CD) is reflected in the diversity of treatment options available for individual patients. The stratification of CD patients into more homogeneous groups based on disease location and disease behavior may provide clinicians with a more focused approach to therapeutic decision-making. Uncomplicated disease behaviors are typically treated medically. When complications arise and patterns of disease become more aggressive, combined medical and surgical approaches are often necessary and yield favorable results. The surgical management of CD can be as complex as the disease itself, and should involve a surgeon who professes a special expertise in inflammatory bowel disease. Progress in our understanding of the role of the interaction between the environment and the immune system in disease development has led to major advancements in the area of CD therapeutics. Current therapies target the various elements of the inflammatory cascade implicated in the pathogenesis of CD. The anti-inflammatory properties of the pharmacologic therapies presented in this review vary from actions that are extremely broad to those that are cellular or cytokine specific. Maximizing the efficacy of CD-directed therapies while minimizing their toxicity remains the principal objective in developing management strategies for CD patients. Maintaining good quality of life and maximizing adherence to therapies are also important considerations. Despite the various therapeutic options available for CD patients, chosen therapies should be based on the overall treatment goal for individual patients. Therapeutics can be broadly categorized as induction therapies (goal to treat active disease) and maintenance therapies (goal to prevent relapse of disease).


Budesonide Main Side Effect Main Drug Interaction Anal Fistula Mesalamine 
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References and Recommended Reading

  1. 1.
    Gasche C, Scholmerich J, Brynskov J, et al.: A simple classification of Crohn’s disease: report of the working party for the World congress of Gastroenterology, Vienna 1998. Inflamm Bowel Dis 2000, 6:8–15.PubMedCrossRefGoogle Scholar
  2. 2.
    Cosnes J, Cattan S, Blain A, et al.: Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis 2002, 8:244–250.PubMedCrossRefGoogle Scholar
  3. 3.
    Louis E, Collard A, Oger AF, et al.: Behaviour of Crohn’s disease according to the Vienna classification: changing pattern over the course of the disease [comment]. Gut 2001, 49:777–782.PubMedCrossRefGoogle Scholar
  4. 4.
    Breuer-Katschinski BD, Hollander N, Goebell H: Effect of cigarette smoking on the course of Crohn’s disease. Eur J Gastroenterol Hepatol 1996, 8:225–228.PubMedCrossRefGoogle Scholar
  5. 5.
    Hanauer SB, Meyers S: Management of Crohn’s disease in adults. Am J Gastroenterol 1997, 92:559–566.PubMedGoogle Scholar
  6. 6.
    Hanauer SB: Review articles: drug therapy: inflammatory bowel disease. N Engl J Med 1996, 334:841–848.PubMedCrossRefGoogle Scholar
  7. 7.
    Summers RW, Switz DM, Sessions JT, et al.: National Cooperative Crohn’s Disease Study: results of drug treatment. Gastroenterology 1979, 77:847–869.PubMedGoogle Scholar
  8. 8.
    Malchow H, Ewe K, Brandes JW, et al.: European Cooperative Crohn’s Disease Study (ECCDS): results of drug treatment. Gastroenterology 1984, 86:249–266.PubMedGoogle Scholar
  9. 9.
    Singleton JW, Hanauer SB, Gitnick GL, et al.: Mesalamine capsules for the treatment of active Crohn’s disease: results of a 16-week trial. Pentasa Crohn’s Disease Study Group. Gastroenterology 1993, 104:1293–1301.PubMedGoogle Scholar
  10. 10.
    Tremaine WJ, Schroeder KW, Harrison JM, Zinsmeister AR: A randomized, double-blind, placebo-controlled trial of the oral mesalamine (5-ASA) preparation, Asacol, in the treatment of symptomatic Crohn’s colitis and ileocolitis. J Clin Gastroenterol 1994, 19:278–282.PubMedCrossRefGoogle Scholar
  11. 11.
    Prantera C, Cottone M, Pallone F, et al.: Mesalamine in the treatment of mild to moderate active Crohn’s ileitis: results of a randomized, multicenter trial. Gastroenterology 1999, 116:521–526.PubMedCrossRefGoogle Scholar
  12. 12.
    Lochs H, Mayer M, Fleig WE, et al.: Prophylaxis of postoperative relapse in Crohn’s disease with mesalamine: European Cooperative Crohn’s Disease Study VI. Gastroenterology 2000, 118:264–273.PubMedCrossRefGoogle Scholar
  13. 13.
    Camma C, Giunta M, Rosselli M, Cottone M: Mesalamine in the maintenance treatment of Crohn’s disease: a meta-analysis adjusted for confounding variables. Gastroenterology 1997, 113:1465–1473.PubMedCrossRefGoogle Scholar
  14. 14.
    Ursing B, Alm T, Barany F, et al.: A comparative study of metronidazole and sulfasalazine for active Crohn’s disease: the cooperative Crohn’s disease study in Sweden. II. Result. Gastroenterology 1982, 83:550–562.PubMedGoogle Scholar
  15. 15.
    Colombel JF, Lemann M, Cassagnou M, et al.: A controlled trial comparing ciprofloxacin with mesalazine for the treatment of active Crohn’s disease. Groupe d’Etudes Therapeutiques des Affections Inflammatoires Digestives (GETAID). Am J Gastroenterol 1999, 94:674–678.PubMedCrossRefGoogle Scholar
  16. 16.
    Greenbloom SL, Steinhart AH, Greenberg GR: Combination ciprofloxacin and metronidazole for active Crohn’s disease. Can J Gastroenterol 1998, 12:53–56.PubMedGoogle Scholar
  17. 17.
    Prantera C, Zannoni F, Scribano ML, et al.: An antibiotic regimen for the treatment of active Crohn’s disease: a randomized, controlled clinical trial of metronidazole plus ciprofloxacin. Am J Gastroenterol 1996, 91:328–332.PubMedGoogle Scholar
  18. 18.
    Sutherland L, Singleton J, Sessions J, et al.: Double blind, placebo controlled trial of metronidazole in Crohn’s disease. Gut 1991, 32:1071–1075.PubMedGoogle Scholar
  19. 19.
    Brandt LJ, Bernstein LH, Boley SJ, Frank MS: Metronidazole therapy for perineal Crohn’s disease: a follow-up study. Gastroenterology 1982, 83:383–387.PubMedGoogle Scholar
  20. 20.
    Rutgeerts P, Hiele M, Geboes K, et al.: Controlled trial of metronidazole treatment for prevention of Crohn’s recurrence after ileal resection. Gastroenterology 1995, 108:1617–1621.PubMedCrossRefGoogle Scholar
  21. 21.
    Barnes PJ: Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci 1998, 94:557–572.PubMedGoogle Scholar
  22. 22.
    Munkholm P, Langholz E, Davidsen M, Binder V: Frequency of glucocorticoid resistance and dependency in Crohn’s disease. Gut 1994, 35:360–362.PubMedGoogle Scholar
  23. 23.
    Rutgeerts P, Lofberg R, Malchow H, et al.: A comparison of budesonide with prednisolone for active Crohn’s disease. N Engl J Med 1994, 331:842–845.PubMedCrossRefGoogle Scholar
  24. 24.
    Greenberg GR, Feagan BG, Martin F, et al.: Oral budesonide for active Crohn’s disease. Canadian Inflammatory Bowel Disease Study Group. N Engl J Med 1994, 331:836–841.PubMedCrossRefGoogle Scholar
  25. 25.
    Campieri M, Ferguson A, Doe W, et al.: Oral budesonide is as effective as oral prednisolone in active Crohn’s disease. The Global Budesonide Study Group. Gut 1997, 41:209–214.PubMedCrossRefGoogle Scholar
  26. 26.
    Thomsen OO, Cortot A, Jewell D, et al.: A comparison of budesonide and mesalamine for active Crohn’s disease. International Budesonide-Mesalamine Study Group. N Engl J Med 1998, 339:370–374.PubMedCrossRefGoogle Scholar
  27. 27.
    Pearson DC: Azathioprine for maintaining remission of Crohn’s disease. Available in The Cochrane Library; Issue 2. Oxford: Update Software; 2000.Google Scholar
  28. 28.
    Sandborn W: Azathioprine or 6-mercaptopurine for inducing remission of Crohn’s disease. Available in The Cochrane Library; Issue 2. Oxford: Update Software; 2000.Google Scholar
  29. 29.
    Present DH, Rutgeerts P, Targan S, et al.: Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999, 340:1398–1405.PubMedCrossRefGoogle Scholar
  30. 30.
    Markowitz J, Grancher K, Kohn N, et al.: A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease. Gastroenterology 2000, 119:895–902. This important paper demonstrates the advantage of early use of 6-mercaptopurine in steroid-treated patients.PubMedCrossRefGoogle Scholar
  31. 31.
    Dubinsky MC, Lamothe S, Yang HY, et al.: Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000, 118:705–713.PubMedCrossRefGoogle Scholar
  32. 32.
    Dubinsky MC, Hassard PV, Seidman EG, et al.: Preliminary evidence suggests that 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease [resubmission]. Gastroenterology 2002, 122:904–915.PubMedCrossRefGoogle Scholar
  33. 33.
    Connell WR: Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease. Lancet 1994, 343:1249–1252.PubMedCrossRefGoogle Scholar
  34. 34.
    Feagan BG, Rochon J, Fedorak RN, et al.: Methotrexate for the treatment of Crohn’s disease. The North American Crohn’s Study Group Investigators. N Engl J Med 1995, 332:292–297.PubMedCrossRefGoogle Scholar
  35. 35.
    Feagan BG, Fedorak RN, Irvine EJ, et al.: A comparison of methotrexate with placebo for the maintenance of remission in Crohn’s disease. N Engl J Med 2000, 342:1627–1632.PubMedCrossRefGoogle Scholar
  36. 36.
    Sandborn W: A critical review of cyclosporine therapy in inflammatory bowel disease. Gastroenterology 1995, 109:1001–1003.PubMedCrossRefGoogle Scholar
  37. 37.
    Feagan BG, McDonald JW, Rochon J, et al.: Low-dose cyclosporine for the treatment of Crohn’s disease. The Canadian Crohn’s Relapse Prevention Trial Investigators. N Engl J Med 1994, 330:1846–1851.PubMedCrossRefGoogle Scholar
  38. 38.
    Fellermann K, Ludwig D, Stahl M, et al.: Steroidunresponsive acute attacks of inflammatory bowel disease: immunomodulation by tacrolimus (FK506). Am J Gastroenterol 1998, 93:1860–1866.PubMedCrossRefGoogle Scholar
  39. 39.
    Sandborn WJ: Preliminary report on the use of oral tacrolimus (FK506) in the treatment of complicated proximal small bowel and fistulizing Crohn’s disease. Am J Gastroenterol 1997, 92:876–879.PubMedGoogle Scholar
  40. 40.
    Casson DH, Eltumi M, Tomlin S, et al.: Topical tacrolimus may be effective in the treatment of oral and perineal Crohn’s disease. Gut 2000, 47:436–440.PubMedCrossRefGoogle Scholar
  41. 41.
    Targan SR, Hanauer SB, van Deventer SJ, et al.: A shortterm study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med 1997, 337:1029–1035.PubMedCrossRefGoogle Scholar
  42. 42.
    Present DH, Rutgeerts P, Targan S, et al.: Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999, 340:1398–1405.PubMedCrossRefGoogle Scholar
  43. 43.
    Hanauer SB, Feagan BG, Lichtenstein GR, et al.: ACCENT I Study Group. Maintenance infliximab for Crohn’s disease: the ACCENT I randomized trial. Lancet 2002, 359:1541–1549. This study demonstrates that anti-tumor necrosis factor _ may be used as a maintenance therapy.PubMedCrossRefGoogle Scholar
  44. 44.
    Sandborn WJ, Hanauer SB, Katz S, et al.: Etanercept for active Crohn’s disease: a randomized, doubleblind, placebo-controlled trial. Gastroenterology 2001, 121:1088–1094.PubMedCrossRefGoogle Scholar
  45. 45.
    Vasiliauskas EA, Kam LY, Abreu-Martin MT, et al.: An open-label pilot study of low-dose thalidomide in chronically active, steroid-dependent Crohn’s disease. Gastroenterology 1999, 117:1278–1287.PubMedCrossRefGoogle Scholar
  46. 46.
    Alsahli M, Jeen TY, Peppercorn MA, et al.: A randomized double-blind, placebo controlled trial of intravenous hydrocortisone in reducing human anti-chimeric antibody following Infliximab therapy. Gastroenterology 2002, 122:A775.Google Scholar
  47. 47.
    Couckuyt H, Gevers AM, Coremans G, et al.: Efficacy and safety of hydrostatic balloon dilation of ileocolonic Crohn’s stricture: a prospective, long-term analysis. Gut 1995, 36:577–580.PubMedGoogle Scholar
  48. 48.
    Broe PJ, Bayless TM, Cameron JL: Crohn’s disease: are enteroenteral fistulas an indication for surgery? Surgery 1982, 91:249–253.PubMedGoogle Scholar
  49. 49.
    Fazio VW, Marchetti F, Church JM, et al.: Effect of resection margins on the recurrence of Crohn’s disease in the small bowel. Ann Surg 1996, 224:563–573.PubMedCrossRefGoogle Scholar
  50. 50.
    Jawhari A, Kamm MA, Ong C, et al.: Intra-abdominal and pelvic abscesses in Crohn’s disease; results of noninvasive and surgical management. Br J Surg 1998, 85:367–371.PubMedCrossRefGoogle Scholar
  51. 51.
    Greenstein AJ, Sachar DB, Pucillo A, et al.: Cancer in Crohn’s disease after diversionary surgery. Am J Surg 1978, 135:86–90.PubMedCrossRefGoogle Scholar
  52. 52.
    Milsom JW, Hammerhofer KA, Bohm B, et al.: Prospective, randomized trial comparing laparoscopic vs. conventional surgery for refractory ileocolic Crohn’s disease. Dis Colon Rectum 2001, 44:1–9. This paper is the first randomized, controlled trial comparing laparoscopic with open surgery for primary ileal or ileocecal Crohn’s disease.PubMedCrossRefGoogle Scholar
  53. 53.
    Duepree HJ, Senagore AJ, Delaney CP, et al.: Advantages of laparoscopic resection for ileocecal Crohn’s disease. Dis Colon Rectum 2002, 45:605–610.PubMedCrossRefGoogle Scholar
  54. 54.
    Allison S, Corman ML: Intestinal stomas in Crohn’s disease. Surgical Clin North Am 2001, 81:185–195.CrossRefGoogle Scholar
  55. 55.
    Fazio VW, Tjandra JJ, Lavery I: Long-term follow-up of stricturoplasty in Crohn’s disease. Dis Colon Rectum 1993, 36:355–361.PubMedCrossRefGoogle Scholar
  56. 56.
    Serra J, Cohen Z, McLeod RS: Natural history of stricturoplasty in Crohn’s disease: 9-year experience. Can J Surg 1995, 38:481–485.PubMedGoogle Scholar
  57. 57.
    Alexander-Williams J: Fistulae-in-ano: Management of Crohn’s fistula. Dis Colon Rectum 1976, 19:518.PubMedCrossRefGoogle Scholar
  58. 58.
    Wolff BG, Culp CE, Beart RW, et al.: Anorectal Crohn’s disease: a long-term perspective. Dis Colon Rectum 1985, 28:709.PubMedCrossRefGoogle Scholar
  59. 59.
    Williams JG, Rothenberger DA, Nemer FD, et al.: Fistula-in-ano in Crohn’s disease: Results of aggressive surgical management. Dis Colon Rectum 1991, 34:378–384.PubMedCrossRefGoogle Scholar
  60. 60.
    Sangwan YP, Schoetz DJ Jr, Murray JJ, et al.: Perianal Crohn’s disease: results of local surgical treatment. Dis Colon Rectum 1996, 39:529.PubMedCrossRefGoogle Scholar
  61. 61.
    Scott HJ, Northover JM: Evaluation of surgery for perianal Crohn’s fistulas. Dis Colon Rectum 1996, 39:1039.PubMedCrossRefGoogle Scholar
  62. 62.
    Joo JS, Weiss EG, Nogueras JJ, et al.: Endorectal advancement flap in perianal Crohn’s disease. Am Surg 1998, 64:147–150.PubMedGoogle Scholar
  63. 63.
    Robertson WG, Mangione JS: Cutaneous advancement flap closure: alternative method for treatment of complicated anal fistulas. Dis Colon Rectum 1998, 41:884.PubMedCrossRefGoogle Scholar
  64. 64.
    Simmang CL, Lacey SW, Huber PJ Jr: Rectal sleeve advancement repair of rectovaginal fistula associated with anorectal stricture in Crohn’s disease. Dis Colon Rectum 1998, 41:787.PubMedCrossRefGoogle Scholar
  65. 65.
    Sonoda T, Hull T, Piedmonte MR, et al.: Outcomes of primary repair of anorectal and rectovaginal fistulas using the endorectal advancement flap. Dis Colon Rectum 2002, 45:1622–1628. This paper describes the results of advancement flaps for anal fistuous disease in over 100 patients.PubMedCrossRefGoogle Scholar
  66. 66.
    Lindsey I, Smilgin-Humphreys MM, Cunningham C, et al.: A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula. Dis Colon Rectum 2002, 45:1608–1615. Excellent article describing the value of fibrin glue for anal fistula.PubMedCrossRefGoogle Scholar
  67. 67.
    Swain BT, Ellis CN Jr: Laparoscopy-assisted loop ileostomy: an acceptable option for temporary fecal diversion after anorectal surgery. Dis Colon Rectum 2002, 45:705–707.PubMedCrossRefGoogle Scholar
  68. 68.
    Williamson PR, Hellinger MD, Larach SW, et al.: Twenty year review of the surgical management of perianal Crohn’s disease. Dis Colon Rectum 1995, 38:389.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2003

Authors and Affiliations

  • Marla C. Dubinsky
    • 1
  • Phillip P. Fleshner
    • 1
  1. 1.Pediatric IBD Center, Cedars-Sinai Medical CenterLos AngelesUSA

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