Gastroenterology
Volume 136, Issue 4 , Pages 1182-1197 , April 2009

Biological Therapies for Inflammatory Bowel Diseases

  • Paul Rutgeerts

      Affiliations

    • Corresponding Author InformationReprint requests Address requests for reprints to: Paul Rutgeerts, MD, PhD, FRCP, AGAF, Division of Gastroenterology, University of Leuven Hospitals, Herestraat 49, 3000 Leuven, Belgium. fax: (32) 16344419
  • ,
  • Severine Vermeire
  • ,
  • Gert Van Assche

Received 3 October 2008 ,Accepted 4 February 2009.

References 

  1. Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007;12:1641–1657
  2. Faubion WA, Loftus EV, Harmsen WS, et al. The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology. 2001;121:255–260
  3. Munkholm P, Langholz E, Davidsen M, et al. Frequency of glucocorticoid resistance and dependency in Crohn's disease. Gut. 1994;35:360–362
  4. Sandborn WJ, Tremaine WJ, Wolf DC, et al. North American Azathioprine Study Group Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn's disease. Gastroenterology. 1999;117:527–535
  5. Ardizzone S, Maconi G, Russo A, et al. Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut. 2006;55:47–53
  6. Feagan BG, Rochon J, Fedorak RN, et al. The North American Crohn's Study Group Investigators Methotrexate for the treatment of Crohn's disease. N Engl J Med. 1995;332:292–297
  7. Feagan BG, Fedorak RN, Irvine EJ, et al. North American Crohn's Study Group Investigators A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. N Engl J Med. 2000;342:1627–1632
  8. Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994;330:1841–1845
  9. Van Assche G, D'Haens G, Noman M, et al. Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology. 2003;125:1025–1031
  10. Moskovitz DN, Van Assche G, Maenhout B, et al. Incidence of colectomy during long-term follow-up after cyclosporine-induced remission of severe ulcerative colitis. Clin Gastroenterol Hepatol. 2006;4:760–765
  11. Sandborn WJ, Hanauer SB, Katz S, et al. Etanercept for active Crohn's disease: Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology. 2001;121:1088–1094
  12. Rutgeerts P, Sandborn WJ, Fedorak RN, et al. Onercept for moderate-to-severe Crohn's disease: a randomized, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2006;4:888–893
  13. Targan SR, Hanauer SB, van Deventer SJ, et al. Crohn's Disease cA2 Study Group A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. N Engl J Med. 1997;337:1029–1035
  14. 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
  15. Rutgeerts P, D'Haens G, Targan S, et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease. Gastroenterology. 1999;117:761–769
  16. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–1549
  17. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med. 2004;350:876–885
  18. Rutgeerts P, Feagan BG, Lichtenstein GR, et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn's disease. Gastroenterology. 2004;126:402–413
  19. Lichtenstein GR, Yan S, Bala M, et al. Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease. Gastroenterology. 2005;128:862–869
  20. Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology. 2007;132:863–873
  21. Borrelli O, Bascietto C, Viola F, et al. Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn's disease. Dig Liver Dis. 2004;36:342–347
  22. Thayu M, Leonard MB, Hyams JS, et al. Improvement in biomarkers of bone formation during infliximab therapy in pediatric Crohn's disease: results of the REACH study. Clin Gastroenterol Hepatol. 2008;6:1378–1384
  23. Sandborn WJ, Rutgeerts P, Reinisch W, et al. SONIC: a randomized, double-blind, controlled trial comparing infliximab and infliximab plus azathioprine to azathioprine in patients with Crohn's disease naive to immunomodulators and biologic therapy. Am J Gastroenterology. 2008;Abstract ACG
  24. Feagan B, McDonald JWD, Panaccione R, et al. A randomized, placebo-controlled study to evaluate the efficacy of infliximab in combination with methotrexate for the long-term treatment of Crohn's disease. Gastroenterology. 2008;135:294;(Abstract)
  25. Van Assche G, Magdelaine-Beuzelin C, D'Haens G, et al. Withdrawal of immunosuppression in Crohn's disease treated with scheduled infliximab maintenance: a randomized trial. Gastroenterology. 2008;134:1861–1868
  26. Schnitzler F, Fidder H, Ferrante M, et al. Long-term outcome of treatment with infliximab in 614 Crohn's disease patients: results from a single centre cohort. Gut. 2008;November (Epub ahead of print)
  27. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476
  28. Jarnerot G, Hertervig E, Friis-Liby I, et al. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005;128:1805–1811
  29. Baert F, Noman M, Vermeire S, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med. 2003;348:601–608
  30. Maser EA, Villela R, Silverberg MS, et al. Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn's disease. Clin Gastroenterol Hepatol. 2006;4:1248–1254
  31. Vermeire S, Noman M, Van Assche G, et al. Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn's disease. Gut. 2007;56:1226–1231
  32. Wu EQ, Mulani PM, Yu AP, et al. Loss of treatment response to infliximab maintenance therapy in Crohn's disease: a payor perspective. Value Health. 2008;May (Epub ahead of print)
  33. Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology. 2006;130:323–333
  34. Sandborn WJ, Hanauer SB, Rutgeerts P, et al. Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial. Gut. 2007;56:1232–1239
  35. 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;132:52–65
  36. Sandborn WJ, Rutgeerts P, Enns R, et al. Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med. 2007;146:829–838
  37. Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007;357:228–238
  38. Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007;357:239–250
  39. Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. Clin Gastroenterol Hepatol. 2006;4:621–630
  40. Fidder HH, Schnitzler F, Ferrante M, et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single center cohort study. Gut. 2008;November
  41. 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;371:660–667
  42. Sandborn WJ, Colombel JF, Enns R, et al. Natalizumab induction and maintenance therapy for Crohn's disease. N Engl J Med. 2005;353:1912–1925
  43. Targan SR, Feagan BG, Fedorak RN, et al. Natalizumab for the treatment of active Crohn's disease: results of the ENCORE Trial. Gastroenterology. 2007;132:1672–1683
  44. Van Assche G, van Ranst M, Sciot R, et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease. N Engl J Med. 2005;353:362–368
  45. Yousry TA, Major EO, Ryschkewitsch C, et al. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med. 2006;354:924–933
  46. Feagan BG, Greenberg GR, Wild G, et al. Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med. 2005;352:2499–2507
  47. Feagan BG, Greenberg GR, Wild G, et al. Treatment of active Crohn's disease with MLN0002, a humanized antibody to the alpha4beta7 integrin. Clin Gastroenterol Hepatol. 2008;6:1370–1371
  48. Mannon PJ, Fuss IJ, Mayer L, et al. Anti-interleukin-12 antibody for active Crohn's disease. N Engl J Med. 2004;351:2069–2079
  49. Sandborn WJ, Feagan BG, Fedorak RN, et al. Ustekinumab Crohn's Disease Study Group A randomized trial of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate to severe Crohn's disease. Gastroenterology. 2008;135:1130–1141
  50. Reinisch W, Hommes DW, Van Assche G, et al. A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease. Gut. 2006;55:1138–1144
  51. Hommes DW, Mikhajlova TL, Stoinov S, et al. Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease. Gut. 2006;55:1131–1137
  52. Ito H, Takazoe M, Fukuda Y, et al. A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease. Gastroenterology. 2004;126:947;989–996
  53. Steidler L, Hans W, Schotte L, et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science. 2000;289:1352–1355
  54. Braat H, Rottiers P, Hommes DW, et al. A phase 1 trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin Gastroenterol Hepatol. 2006;4:754–759
  55. Pena-Rossi C, Schreiber S, Golubovic G, et al. Clinical trial: a multicentre, randomized, double-blind, placebo-controlled, dose-finding, phase II study of subcutaneous interferon-beta-1a in moderately active ulcerative colitis. Aliment Pharmacol Ther. 2008;28:758–767
  56. Stronkhorst A, Radema S, Yong SL, et al. CD4 antibody treatment in patients with active Crohn's disease: a phase 1 dose finding study. Gut. 1997;40:320–327
  57. Plevy S, Salzberg B, Van Assche G, et al. A phase I study of visilizumab, a humanized anti-CD3 monoclonal antibody, in severe steroid-refractory ulcerative colitis. Gastroenterology. 2007;133:1414–1422
  58. Kasran A, Boon L, Wortel CH, et al. Safety and tolerability of antagonist anti-human CD40 Mab ch5D12 in patients with moderate to severe Crohn's disease. Aliment Pharmacol Ther. 2005;22:111–122
  59. Van Assche G, Dalle I, Noman M, et al. A pilot study on the use of the humanized anti-interleukin-2 receptor antibody daclizumab in active ulcerative colitis. Am J Gastroenterol. 2003;98:369–376
  60. Van Assche G, Sandborn WJ, Feagan BG, et al. Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial. Gut. 2006;55:1568–1574
  61. Creed TJ, Probert CS, Norman MN, et al. Basiliximab for the treatment of steroid-resistant ulcerative colitis: further experience in moderate and severe disease. Aliment Pharmacol Ther. 2006;23:1435–1442
  62. Korzenik JR, Dieckgraefe BK, Valentine JF, et al. Sargramostim for active Crohn's disease. N Engl J Med. 2005;352:2193–2201
  63. Feagan BG, Anderson F, Radford-Smith GL, et al. Efficacy and safety of sargramostim in moderate to severe Crohn's disease: results of N.O.V.E.L 4, a phase III multicenter study. Gastroenterology 132(Suppl 2):A103
  64. Sandborn WJ, Sands BE, Wolf DC, et al. Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial. Aliment Pharmacol Ther. 2003;17:1355–1364
  65. Sinha A, Nightingale J, West KP, et al. Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis. N Engl J Med. 2003;349:350–357
  66. Slonim AE, Bulone L, Damore MB, et al. A preliminary study of growth hormone therapy for Crohn's disease. N Engl J Med. 2000;342:1633–1637
  67. Hommes D, van den Blink B, Plasse T, et al. Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn's disease. Gastroenterology. 2002;122:7–14
  68. Schreiber S, Feagan B, D'Haens G, et al. Oral p38 mitogen-activated protein kinase inhibition with BIRB 796 for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2006;4:325–334
  69. Travis S, Yap LM, Hawkey C, et al. RDP58 is a novel and potentially effective oral therapy for ulcerative colitis. Inflamm Bowel Dis. 2005;11:713–719
  70. Lewis JD, Lichtenstein GR, Deren JJ, et al. Rosiglitazone for Ulcerative Colitis Study Group Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial. Gastroenterology. 2008;134:688–695
  71. Burakoff R, Barish CF, Riff D, et al. A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease. Inflamm Bowel Dis. 2006;12:558–565
  72. Keshav S, Wolf D, Katz S, et al. CCX282-B, an orally active inhibitor of chemokine receptor CCR9, in a randomized, double-blind, placebo-controlled phase 2 study in moderate to severe Crohn's disease. Gut. 2006;A22:OP-G-93
  73. Mackey AC, Green L, Liang LC, et al. Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007;44:265–267
  74. Feagan BG, Panaccione R, Sandborn WJ, et al. Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM study. Gastroenterology. 2008;135:1493–1499
  75. Lemann M, Mary JY, Duclos B, et al. Infliximab plus azathioprine for steroid-dependent Crohn's disease patients: a randomized placebo-controlled trial. Gastroenterology. 2006;130:1054–1061

 Conflicts of interest The authors disclose no conflicts.

 Funding Professor Rutgeerts consults, has received research support, and has lectured for Centocor, Schering Plough, Union Chimique Belge Brussels Belgium, and Abbott; and consulted for Elan-Biogen, PDL, Avidia, Bristol Myers Squibb, Millenium Pharmaceuticals, Genetech, Novimmune, and Cheocentrix. Dr Van Assche has received research support from Abbott; honoraria or speaking fees from UCB, Schering-Plough, and Abbott; and consulted for Novartis, Centocor, and Schering-Plough. Dr Vermeire has received research support from UCB (Chair); and honoraria/speaking fees from UCB, Abbott, and Schering-Plough.

PII: S0016-5085(09)00177-2

doi: 10.1053/j.gastro.2009.02.001

Gastroenterology
Volume 136, Issue 4 , Pages 1182-1197 , April 2009