Journal Mobile Options
Table of Contents
Vol. 71, No. 1, 2005
Issue release date: 2005

Severe and Steroid-Resistant Crohn’s Disease

Michetti P. · Mottet C. · Juillerat P. · Felley C. · Vader J.-P. · Burnand B. · Gonvers J.-J. · Froehlich F.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Patients with moderate to severe disease and patients with steroid-refractory or steroid-dependent disease differ in their management, as the latter groups usually include patients with less acute situations. Systemic corticosteroids represent the mainstay of the management of moderate to severe disease and remain the first-line therapy in this setting. Infliximab is the choice alternative for patients who do not respond to steroids or in whom steroids are contraindicated. Purine analogues, methotrexate and infliximab have shown efficacy in achieving steroid-free remission in patients with steroid-refractory or -dependent disease. Other fast-acting immunosuppressors showed little benefit. Surgery may be indicated in this setting. Nataluzimab may prove useful in patients refractory to infliximab.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Hanauer SB, Sandborn W: Management of Crohn’s disease in adults. Am J Gastroenterol 2001;96:635–643.
  2. Munkholm P, et al: Frequency of glucocorticoid resistance and dependency in Crohn’s disease. Gut 1994;35:360–362.
  3. Faubion WA Jr, et al: The natural history of corticosteroid therapy for inflammatory bowel disease: A population-based study. Gastroenterology 2001;121:255–260.
  4. Franchimont DP, et al: Clinical pattern of corticosteroid dependent Crohn’s disease. Eur J Gastroenterol Hepatol 1998;10:821–825.
  5. Bernstein CN, Shanahan, F: Critical appraisal of enteral nutrition as primary therapy in adults with Crohn’s disease. Am J Gastroenterol 1996;91:2075–2079.
  6. Han PD, et al: Nutrition and inflammatory bowel disease. Gastroenterol Clin North Am 1999;28:423–443, ix.
  7. Malchow H, et al: European Cooperative Crohn’s Disease Study (ECCDS): Results of drug treatment. Gastroenterology 1984;86:249–266.
  8. Summers RW, et al: National Cooperative Crohn’s Disease Study: Results of drug treatment. Gastroenterology 1979;77:847–869.
  9. Shepherd HA, Barr, GD, Jewell DP: Use of an intravenous steroid regimen in the treatment of acute Crohn’s disease. J Clin Gastroenterol 1986;8:154–159.
  10. Felder JB, Adler DJ, Korelitz BI: The safety of corticosteroid therapy in Crohn’s disease with an abdominal mass. Am J Gastroenterol 1991;86:1450–1455.
  11. Chun A, et al: Intravenous corticotrophin vs. hydrocortisone in the treatment of hospitalized patients with Crohn’s disease: A randomized double-blind study and follow-up. Inflamm Bowel Dis 1998;4:177–181.
  12. Van Dullemen HM, et al: Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 1995;109:129–135.
  13. Targan SR, et al: A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor-α for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med 1997;337:1029–1035.
  14. Farrell RJ, et al: Clinical experience with infliximab therapy in 100 patients with Crohn’s disease. Am J Gastroenterol 2000;95:3490–3497.
  15. Cohen RD, Tsang JF, Hanauer SB: Infliximab in Crohn’s disease: First anniversary clinical experience. Am J Gastroenterol 2000;95:3469–3477.
  16. Hanauer SB, et al: Maintenance infliximab for Crohn’s disease: The ACCENT I randomised trial. Lancet 2002;359:1541–1549.
  17. Baert F, et al: Autoimmunity associated with anti-tumor necrosis factor-α treatment in Crohn’s disease: A prospective cohort study. N Engl J Med 2003;348:601–608.
  18. Farrell RJ, et al: Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: A randomized controlled trial. Gastroenterology 2003;124:917–924.
  19. Brynskov J, et al: A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn’s disease. N Engl J Med 1989;321:845–850.
  20. Jewell DP, Lennard-Jones JE, and the Cyclosporine Study Group of Great Britain and Ireland: Oral cyclosporine for chronic active Crohn’s disease. A multicenter controlled trial. Eur J Gastroenterol Hepatol 1994;6:499–505.

    External Resources

  21. Feagan BG, 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.
  22. Stange EF, et al: European trial of cyclosporine in chronic active Crohn’s disease: A 12- month study. The European Study Group. Gastroenterology 1995;109:774–782.
  23. Hermida-Rodriguez C, et al: High-dose intravenous cyclosporine in steroid refractory attacks of inflammatory bowel disease. Hepatogastroenterology 1999;46:2265–2268.
  24. Santos JV, et al: Intravenous cyclosporine for steroid-refractory attacks of Crohn’s disease. Short- and long-term results. J Clin Gastroenterol 1995;20:207–210.
  25. Egan LJ, Sandborn WJ, Tremaine WJ: Clinical outcome following treatment of refractory inflammatory and fistulizing Crohn’s disease with intravenous cyclosporine. Am J Gastroenterol 1998;93:442–448.
  26. 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.
  27. Hafraoui S, et al: Mycophenolate mofetil in refractory Crohn’s disease after failure of treatments by azathioprine or methotrexate (in French). Gastroenterol Clin Biol 2002;26:17–22.
  28. Hassard PV, et al: Efficacy of mycophenolate mofetil in patients failing 6-mercaptopurine or azathioprine therapy for Crohn’s disease. Inflamm Bowel Dis 2000;6:16–20.
  29. Miehsler W, et al: Is mycophenolate mofetil an effective alternative in azathioprine-intolerant patients with chronic active Crohn’s disease? Am J Gastroenterol 2001;96:782–787.
  30. Neurath MF, et al: Randomised trial of mycophenolate mofetil versus azathioprine for treatment of chronic active Crohn’s disease. Gut 1999;44:625–628.
  31. Gonzalez-Huix F, et al: Polymeric enteral diets as primary treatment of active Crohn’s disease: A prospective steroid controlled trial. Gut 1993;34:778–782.
  32. Fukuda Y, et al: Efficacy of nutritional therapy for active Crohn’s disease. J Gastroenterol 1995;30(suppl 8):83–87.

    External Resources

  33. Lindor KD, et al: A randomized prospective trial comparing a defined formula diet, corticosteroids, and a defined formula diet plus corticosteroids in active Crohn’s disease. Mayo Clin Proc 1992;67:328–333.
  34. Lochs H, et al: Comparison of enteral nutrition and drug treatment in active Crohn’s disease. Results of the European Cooperative Crohn’s Disease Study. IV. Gastroenterology 1991;101:881–888.
  35. Malchow H, et al: Feasibility and effectiveness of a defined-formula diet regimen in treating active Crohn’s disease. European Cooperative Crohn’s Disease Study III. Scand J Gastroenterol 1990;25:235–244.
  36. O’Keefe SJ, et al: Steroids and bowel rest versus elemental diet in the treatment of patients with Crohn’s disease: The effects on protein metabolism and immune function. JPEN J Parenter Enteral Nutr 1989;13:455–460.
  37. O’Morain C, Segal AW, Levi AJ: Elemental diet as primary treatment of acute Crohn’s disease: A controlled trial. Br Med J Clin Res Ed 1984;288:1859–1862.
  38. Fernandez-Banares F, et al: 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;19:356–364.
  39. Griffiths AM, et al: Meta-analysis of enteral nutrition as a primary treatment of active Crohn’s disease. Gastroenterology 1995;108:1056–1067.
  40. Messori A, et al: Defined-formula diets versus steroids in the treatment of active Crohn’s disease: A meta-analysis. Scand J Gastroenterol 1996;31:267–272.
  41. Bernell O, Lapidus A, Hellers G: Risk factors for surgery and recurrence in 907 patients with primary ileocaecal Crohn’s disease. Br J Surg 2000;87:1697–1701.
  42. Lautenbach E, Berlin JA, Lichtenstein GR: Risk factors for early postoperative recurrence of Crohn’s disease. Gastroenterology 1998;115:259–267.
  43. Poggioli G, et al: Review article: Indication and type of surgery in Crohn’s disease. Aliment Pharmacol Ther 2002;16(suppl 4):59–64.
  44. Milsom JW, et al: Prospective, randomized trial comparing laparoscopic vs. conventional surgery for refractory ileocolic Crohn’s disease. Dis Colon Rectum 2001;44:1–9.
  45. Scott NA, Hughes LE: Timing of ileocolonic resection for symptomatic Crohn’s disease – The patient’s view. Gut 1994;35:656–657.
  46. Binder V, Hendriksen C, Kreiner S: Prognosis in Crohn’s disease based on results from a regional patient group from the county of Copenhagen. Gut 1985;26:146–150.
  47. Present DH, et al: Treatment of Crohn’s disease with 6-mercaptopurine. A long-term, randomized, double-blind study. N Engl J Med 1980;302:981–987.
  48. Oren R, et al: Methotrexate in chronic active Crohn’s disease: A double-blind, randomized, Israeli multicenter trial. Am J Gastroenterol 1997;92:2203–2209.
  49. Willoughby JM, et al: Controlled trial of azathioprine in Crohn’s disease. Lancet 1971;ii:944–947.
  50. Rhodes J, et al: Controlled trial of azathioprine in Crohn’s disease. Lancet 1971;ii:1273–1276.
  51. Ewe K, et al: Azathioprine combined with prednisolone or monotherapy with prednisolone in active Crohn’s disease. Gastroenterology 1993;105:367–732.
  52. Candy S, et al: A controlled double-blind study of azathioprine in the management of Crohn’s disease. Gut 1995;37:674–678.
  53. Klein M, et al: Treatment of Crohn’s disease with azathioprine: A controlled evaluation. Gastroenterology 1974;66:916–922.
  54. Pearson DC, et al: Azathioprine and 6-mercaptopurine in Crohn’s disease – A meta-analysis. Ann Intern Med 1995;123:132–142.
  55. O’Donoghue DP, et al: Double-blind withdrawal trial of azathioprine as maintenance treatment for Crohn’s disease. Lancet 1978;ii:955–957.

    External Resources

  56. Sandborn W, Sutherland L, Pearson D, May G, Modigliani R, Prantera C: Azathioprine or 6-mercaptopurine for induction of remission in Crohn’s disease (Cochrane review). Update Software. Oxford, The Cochrane Library, 2003.
  57. Arora S, et al: Methotrexate in Crohn’s disease: Results of a randomized, double-blind, placebo-controlled trial. Hepatogastroenterology 1999;46:1724–1729.
  58. Feagan BG, 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.
  59. Vandeputte L, et al: Methotrexate in refractory Crohn’s disease. Inflamm Bowel Dis 1999;5:11–15.
  60. Lemann M, et al: Methotrexate for the treatment of refractory Crohn’s disease. Aliment Pharmacol Ther 1996;10:309–314.
  61. Kozarek RA, et al: Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease. Ann Intern Med 1989;110:353–356.
  62. Ricart E, et al: Infliximab for Crohn’s disease in clinical practice at the Mayo Clinic: The first 100 patients. Am J Gastroenterol 2001;96:722–729.
  63. Cohen RD: Efficacy and safety of repeated infliximab infusions for Crohn’s disease: One-year clinical experience. Inflamm Bowel Dis 2001;7(suppl 1):17–22.
  64. Hommes DW, et al: Infliximab treatment for Crohn’s disease: One-year experience in a Dutch academic hospital. Inflamm Bowel Dis 2002;8:81–86.
  65. Panis Y: Prise en charge chirurgicale des maladies inflammatoires chroniques de l’intestin: les consensus et les controverses. Gastroenterol Clin Biol 2003;27(suppl 3):92–97.
  66. Ghosh S, et al: Natalizumab for active Crohn’s disease. N Engl J Med 2003;348:24–32.
  67. Gordon F, et al: A randomized placebo-controlled trial of a humanized monoclonal antibody to α4 integrin in active Crohn’s disease. Gastroenterology 2001;121:268–274.
  68. Rutgeerts P, et al: Subanalyses from a phase 3 study on the evaluation of natalizumab in active Crohn’s disease therapy-1 (ENACT-1). Gut 2003;52(suppl 6):A239

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50