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Promising New Agents for the Treatment of Inflammatory Bowel Disorders

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  • Section 2: Inflammatory Bowel Disorders
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Abstract

A groundswell of therapeutic modalities is presently sweeping through the field of inflammatory bowel disease (IBD), revolutionising the treatment and management of these disorders. At the forefront of newer agents are biological therapies, also referred to as ‘biologics’. These include infliximab (cA2), CDP 571, rhIL-10, ICAM-1 antisense oligonucleotide (ISIS 2302) and opreleukin (rhIL-11).

Among these, infliximab and CDP 571 are perhaps the most promising, particularly in Crohn’s disease. Both are anti-TNFa monoclonal antibody formulations with proven efficacy at doses of 5 mg/kg for inducing remission in patients with moderate to severe refractory Crohn’s disease. Infliximab is beneficial in the treatment of fistulous Crohn’s disease as well. Anti-inflammatory cytokines such as rhIL-10 and opreleukin (rhIL-11) in early reports appear efficacious in Crohn’s disease but not in ulcerative colitis.

Budesonide, a second generation glucocorticoid, in an oral controlled ileal release capsule, is an attractive alternative to prednisone for treating active Crohn’s disease of the distal ileum and proximal colon. Also available as an enema, budesonide’s efficacy approximates that of prednisolone for inducing remission in active distal ulcerative colitis.

Postoperative recurrences of Crohn’s disease are a common clinical scenario. Recently, mesalazine, metronidazole and mercaptopurine have been re-evaluated in the postoperative setting. In the largest postoperative prophylaxis trial, mercaptopurine was superior to both placebo and mesalazine in preventing clinical, endoscopic and radiographic relapses.

Finally, miscellaneous therapies such as transdermal nicotine, nicotine tartrate enemas and topical lidocaine used in pilot studies for ulcerative colitis have shown promise. Case reports of thalidomide and tacrolimus (FK 506) have reported beneficial effects in treating complicated, refractory Crohn’s disease.

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References

  1. Derkx B, Taminiau J, Radema S, et al. Tumour-necrosis-factor antibody treatment in Crohn’s disease [letter]. Lancet 1993; 342 (8864): 173–4

    CAS  Google Scholar 

  2. van Dullemen HM, van Deventer SJ, Hommes DW, et al. Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 1995; 109 (1): 129–35

    Article  PubMed  Google Scholar 

  3. Targan SR, Hanauer SB, van Deventer SJH, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. N Engl J Med 1997; 337 (15): 1029–35

    Article  PubMed  CAS  Google Scholar 

  4. Stack WA, Mann SD, Roy AJ, et al. Randomised controlled trial of CDP 571 antibody to tumour necrosis factor-alpha in Crohn’s disease. Lancet 1997; 349 (9051): 521–4

    Article  PubMed  CAS  Google Scholar 

  5. Rutgeerts P, D’Haens G, van Deventer SJH, et al. Retreatment with anti-TNF-alpha chimeric antibody (cA2) effectively maintains cA2-induced remission in Crohn’s disease [abstract]. Gastroenterology 1997; 112 (4): A1078

    Article  Google Scholar 

  6. Present D, Mayer L, VanDeventer SJH, et al. Anti-TNF-alpha chimeric antibody (cA2) is effective in the treatment of the fistulae of Crohn’s disease: a multicenter, randomized, double-blind, placebo-controlled study [abstract]. Am J Gastroenterol 1997; 92 (9): 1746

    Google Scholar 

  7. Plevy SE, Taylor K, DeWoody KL, et al. Tumor necrosis factor (TNF) microsatellite haplotypes and perinuclear anti-neutrophil cytoplasmic antibody (pANCA) identify Crohn’s disease (CD) patients with poor clinical responses to anti-TNF monoclonal antibody (cA2) [abstract]. Gastroenterology 1997; 112 (4): A1062

    Google Scholar 

  8. Infliximab package insert. Malvern (PA): Centocor Inc.

  9. Van Deventer SJH, Elson CO, Fedorak RN. Multiple doses of intravenous interleukin 10 in steroid refractory Crohn’s disease. Gastroenterology 1997; 113: 383–9

    Article  PubMed  Google Scholar 

  10. Fedorak RN, Gangl A, Elson CO, et al. Safety, tolerance and efficacy of multiple doses of subcutaneous interleukin-10 in mild to moderate active Crohn’s disease (STAMM-CD) [abstract]. Gastroenterology 1998; 114 (4): A974

    Article  Google Scholar 

  11. Bank S, Sninsky C, Robinson M, et al. Safety and activity evaluation of rh IL-11 in subjects with active Crohn’s disease [abstract]. Gastroenterology 1997; 112 (4): A927

    Google Scholar 

  12. Schreiber S, Fedorak RN, Wild G, et al. Safety and tolerance of rhIL-10 treatment in patients with mild/moderate active ulcerative colitis [abstract]. Gastroenterology 1998; 114 (4): G4424

    Google Scholar 

  13. Yacyshyn BR, Bowen-Yacyshyn MB, Jewell L, et al. A placebocontrolled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn’s disease. Gastroenterology 1998; 114: 1133–42

    Article  PubMed  CAS  Google Scholar 

  14. Campieri M, Ferguson A, Doe W, et al. Oral budesonide is as effective as oral prednisolone in active Crohn disease. Gut 1997; 41: 209–14

    Article  PubMed  CAS  Google Scholar 

  15. 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 (13): 836–41

    Article  PubMed  CAS  Google Scholar 

  16. Thomsen OO, Cortot A, Jewell D, et al. A comparison of budesonide and mesalamine for active Crohn’s disease. New Engl J Med 1998; 339: 370–4

    Article  PubMed  CAS  Google Scholar 

  17. Bar-Meir S, Israeli Budesonide Study Group. Budesonide (BUD) versus prednisone (pred) in the treatment of active Crohn’s disease (CD): a double-blind controlled trial [abstract]. Gastroenterology 1998; 114 (4): A926

    Article  Google Scholar 

  18. Lofberg R, Danielsson A, Salde L. Oral budesonide in active Crohn’s disease. Aliment Pharmacol Ther 1993; 7 (6): 611–6

    Article  PubMed  CAS  Google Scholar 

  19. Caesar I, Gross V, Roth M, et al. Treatment of active Crohn’s ileocolitis with oral pH-modified budesonide. Germany Budesonide Study Group. Z Gastroenterol 1995; 33 (5): 247–50

    CAS  Google Scholar 

  20. Gross V, Caesar T, Andrus H, et al. Dose-finding study with oral budesonide in patients with active Crohn’s ileocolitis [abstract]. Gastroenterology 1997; 112 (4): A986

    Google Scholar 

  21. Gross V, Caesar I, Andrus T, et al. Replacement of systemic steroids by oral budesonide in patients with post-active or chronic Crohn’s ileocolitis: a dose-finding study [abstract]. Gastroenterology 1997; 112 (4): A987

    Google Scholar 

  22. Greenberg GR, Feagan BG, Martin F, et al. Oral budesonide as maintenance treatment for Crohn’s disease: a placebo-controlled, dose-ranging study: Canadian Inflammatory Bowel Disease Study Group. Gastroenterology 1996; 110 (1): 45–51

    Article  PubMed  CAS  Google Scholar 

  23. Gross V, Andus T, Caesar I, et al. Oral pH-modified release budesonide versus 6-methylprednisolone in active Crohn’s disease. German/Austrian Budesonide Study Group. Eur J Gastroenterol Hepatol 1996; 8 (9): 905–9

    PubMed  CAS  Google Scholar 

  24. Hanauer SB, Robinson M, Pruitt R, et al. Budesonide enema for the treatment of active, distal ulcerative colitis and proctitis: a dose-ranging study. Gastroenterology 1998; 115: 525–32

    Article  PubMed  CAS  Google Scholar 

  25. Lemann M, Galian A, Rutgeerts P, et al. Comparison of budesonide and 5-aminosalicylic acid enemas in active distal ulcerative colitis. Aliment Pharmacol Ther 1995; 9 (5): 557–62

    Article  PubMed  CAS  Google Scholar 

  26. Loftberg R, Ostergaard TO, Langholtz E, et al. Budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Aliment Pharmacol Ther 1994; 8 (6): 623–9

    Article  Google Scholar 

  27. Marshall JK, Irvine EJ. Rectal corticosteroids versus alternative treatments in ulcerative colitis: a meta-analysis. Gut 1997; 40 (6): 775–81

    Article  PubMed  CAS  Google Scholar 

  28. Lofberg R, Danielsson A, Suhr O, et al. Oral budesonide versus prednisolone in patients with active extensive and left-sided ulcerative colitis. Gastroenterology 1996; 110: 1713–8

    Article  PubMed  CAS  Google Scholar 

  29. Brignola C, Cottone M, Pera A, et al. Mesalamine in the prevention of endoscopic recurrence after intestinal resection for Crohn’s disease: Italian Cooperative Study Group. Gastroenterology 1995; 108 (2): 345–9

    Article  PubMed  CAS  Google Scholar 

  30. McLeod RS, Wolff BG, Steinhart AH, et al. Prophylactic mesalamine treatment decreases postoperative recurrence of Crohn’s disease. Gastroenterology 1995; 109 (2): 404–13

    Article  PubMed  CAS  Google Scholar 

  31. Lochs H, Mayer M, Fleig WE, et al. Prophylaxis of postoperative relapse in Crohn’s disease with mesalazine (Pentasa) in comparison to placebo [abstract]. Gastroenterology 1997; 112 (4): A1027

    Google Scholar 

  32. 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 (6): 1617–21

    Article  PubMed  CAS  Google Scholar 

  33. Lemann M, Cuillerier E, Bouhnik Y, et al. Azathioprine (AZA) for prevention of Crohn’s recurrence after ileal or colonic resection [abstract]. Gastroenterology 1996; 110 (4): A948

    Google Scholar 

  34. Korelitz B, Hanauer S, Rutgeerts P, et al. Post-operative prophylaxis with 6-MP, 5-ASA or placebo in Crohn’s disease: a 2 year multicenter trial. Gastroenterology. In press

  35. Sandborn WJ, Van OE, Zins BJ, et al. An intravenous loading dose of azathioprine decreases the time to response in patients with Crohn’s disease. Gastroenterology 1995; 109 (6): 1808–17

    Article  PubMed  CAS  Google Scholar 

  36. Sandborn WJ, Tremaine WJ, Offord KP, et al. Transdermal Nicotine for mildly to mderately active ulcerative colitis. Ann Intern Med 1997; 126: 364–71

    PubMed  CAS  Google Scholar 

  37. Pullan RD, Rhodes J, Ganesh S, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med 1994; 330: 811–5

    Article  PubMed  CAS  Google Scholar 

  38. Thomas GA, Rhodes J, Ragunath K, et al. Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis. Eur J Gastroenterol Hepatol 1996; 8: 769–76

    PubMed  CAS  Google Scholar 

  39. Thomas GA, Rhodes J, Mani V, et al. Transdermal nicotine as maintenance therapy for ulcerative colitis. N Engl J Med 1995; 332: 988–92

    Article  PubMed  CAS  Google Scholar 

  40. Sandborn WJ, Tremaine W, Hurt RD. Open maintenance treatment with transdermal nicotine: long-term results after a randomized, double-blind, placebo-controlled trial for active ulcerative colitis [abstract]. Gastroenterology 1998; 114: G4401

    Google Scholar 

  41. Sandborn WJ, Tremaine WJ, Leighton JA, et al. Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study. Aliment Pharmacol Ther 1997; 11 (4): 663–71

    Article  PubMed  CAS  Google Scholar 

  42. Saibil F. Novel therapies for Crohn disease and colitis [letter]. Can Med Assoc J 1997; 156 (5): 634–6

    CAS  Google Scholar 

  43. Bjorck S, Dahlstrom A, Johansson L, et al. Treatment of the mucosa with local anaesthetics in ulcerative colitis. Agents Actions 1992; Spec. No.: C60–72

    Google Scholar 

  44. Odeka LB, Miller V. Thalidomide in oral Crohn’s disease refractory to conventional medical treatment [letter]. J Pediatr Gastroenterol Nutr 1997; 25 (2): 250–1

    Google Scholar 

  45. Wettstein AR, Meagher AP. Thalidomide in Crohn’s disease. Lancet 1997; 350: 1445–6

    Article  PubMed  CAS  Google Scholar 

  46. 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 (5): 876–9

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology, Wilford Hall Medical Center, Lackland AFB, Texas, USA

    Kevin A. Lang

  2. Department of Medicine, University of Texas Health Science Center, ]San Antonio, Texas, USA

    Kevin A. Lang

  3. Harvard Medical School, Boston, Massachusetts, USA

    Mark A. Peppercorn

  4. Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

    Mark A. Peppercorn

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  1. Kevin A. Lang
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  2. Mark A. Peppercorn
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Correspondence to Mark A. Peppercorn.

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Lang, K.A., Peppercorn, M.A. Promising New Agents for the Treatment of Inflammatory Bowel Disorders. Drugs R&D 1, 237–244 (1999). https://doi.org/10.2165/00126839-199901030-00011

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