Skip to main content

Biologics in Crohn’s Disease and Ulcerative Colitis: Focus on Tumor Necrosis Factor Antagonists

  • Chapter
Biologics in General Medicine
  • 1376 Accesses

Abstract

Elucidation of the cellular and molecular mediators of tissue injury in Crohn’s disease (CD) and ulcerative colitis (UC) has expanded the potential management options for these diseases. The discovery of immunologic and inflammatory mediators, in particular, has paved the way for clinical research with biologic agents in this area. Although conventional treatments remain viable options for some patients, those who are intolerant to these agents and those with more serious or refractory disease may require newer biologic therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anderson PJ (2005) Tumor necrosis factor inhibitors: clinical implications of their different immunogenicity profiles. Semin Arthritis Rheum 34(5 Suppl 1):19–22

    Article  PubMed  CAS  Google Scholar 

  • Baert F, Noman M, Vermeire S, et al. (2003) Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med 348:601–608

    Article  PubMed  CAS  Google Scholar 

  • Baert F, Vermeire S, Noman M, et al. (2004) Management of ulcerative colitis and Crohn’s disease. Acta Clin Belg 59:304–314

    PubMed  CAS  Google Scholar 

  • Barthel HR, Gille T, Halbsguth A, Kramer M (2005) Successful treatment with adalimumab in infliximab-resistant Crohn’s disease. J Gastroenterol Hepatol 20:1464–1465

    Article  PubMed  Google Scholar 

  • Bayless T, Talamini M, Kaufman H, et al. (2006) Digestive disease library: Colon & rectum, Crohn’s disease. Available at: http://hopkins-gi.nts.jhu.edu/pages/latin/templates/index.cfm?pg=disease1&organ=6&disease=21&lang_id=1. Accessed April 17, 2006

    Google Scholar 

  • Braegger CP, Nicholls S, Murch SH, et al. (1992) Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet 339:89–91

    Article  PubMed  CAS  Google Scholar 

  • Buhner S, Buning C, Genschel J, et al. (2006) Genetic basis for increased intestinal permeability in families with Crohn’s disease: role of CARD15 3020insC mutation? Gut 55:342–347

    Article  PubMed  CAS  Google Scholar 

  • Calenda KA, Schornagel IL, Sadeghi-Nejad A, Grand RJ (2005) Effect of recombinant growth hormone treatment on children with Crohn’s disease and short stature: a pilot study. Inflamm Bowel Dis 11:435–441

    Article  PubMed  Google Scholar 

  • Catrina AI, Trollmo C, af Klint E, et al. (2005) Evidence that anti-tumor necrosis factor therapy with both etanercept and infliximab induces apoptosis in macrophages, but not lymphocytes, in rheumatoid arthritis joints: extended report. Arthritis Rheum 52:61–72

    Article  PubMed  CAS  Google Scholar 

  • Colombel JF, Sandborn WJ, Rutgeerts P, et al. (2006) Adalimumab induces and maintains clinical response and remission in patients with active Crohn’s disease: results of the CHARM trial [abstract 686d]. Presented at Digestive Disease Week 2006, Los Angeles, California, May 23, 2006

    Google Scholar 

  • Cucchiara S, Romeo E, Viola F, et al. (2006) Infliximab as a first choice therapy in children with newly diagnosed Crohn’s disease (CD) promotes long-term sustained remission and alters the course of the disease [abstract 56]. Presented at Digestive Disease Week 2006, Los Angeles, California, May 21, 2006

    Google Scholar 

  • Dieckgraefe BK, Korzenik JR (2002) Treatment of active Crohn’s disease with recombinant human granulocyte-macrophage colony-stimulating factor. Lancet 360:1478–1480

    Article  PubMed  Google Scholar 

  • Dignass A, Targan S, Salzberg B, et al. (2004) Visilizumab, a humanized anti CD3 monoclonal antibody is active in the treatment of severe steroid refractory ulcerative colitis: preliminary results of a phase I-II study. Gut 52(SupplVI):A54

    Google Scholar 

  • Feagan BG, Greenberg G, Wild G, et al. (2003) Efficacy and safety of a humanized α4β7 antibody in active Crohn’s disease (CD). Gastroenterology 124(Suppl 1):A25 (Abstract 178)

    Article  Google Scholar 

  • Feagan BG, Greenberg GR, Wild G, et al. (2005) Treatment of ulcerative colitis with a humanized antibody to the α4β7 integrin. N Engl J Med 352:2499–2507

    Article  PubMed  CAS  Google Scholar 

  • Fossati G, Nesbitt AM (2005a) Effect of the anti-TNF agents, adalimumab, etanercept, infliximab, and certolizumab PEGOL (CDP870) on the induction of apoptosis in activated peripheral blood lymphocytes and monocytes. Am J Gastroenterol 100:S287

    Article  Google Scholar 

  • Fossati G, Nesbitt AM (2005b) In vitro complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by the anti-TNF agents adalimumab, etanercept, infliximab, and certolizumab pegol (CDP870). Am J Gastroenterol 100:S287

    Article  Google Scholar 

  • Ghosh S, Goldin E, Gordon FH, et al. (2003) Natalizumab for active Crohn’s disease. N Engl J Med 348:24–32

    Article  PubMed  CAS  Google Scholar 

  • Gordon FH, Lai CS, Hamilton MI, et al. (2001) A randomized placebo-controlled trial of a humanized monoclonal antibody to alpha4 integrin in active Crohn’s disease. Gastroenterology 121:268–274

    Article  PubMed  CAS  Google Scholar 

  • Granneman RG, Zhang Y, Noetersheuser PA, et al. (2003) Pharmacokinetic/pharmacodynamic (PK/PD) relationships of adalimumab (Humira™, Abbott) in rheumatoid arthritis patients during Phase II/III clinical trials [abstract]. Arthritis Rheum 48(Suppl):S140 (Poster 256)

    Google Scholar 

  • Hanauer SB, Feagan BG, Lichtenstein GR, et al. (2002) Maintenance infliximab for Crohn’s disease: the ACCENT I randomized trial. Lancet 359:1541–1549

    Article  PubMed  CAS  Google Scholar 

  • Hanauer SB, Present DH (2003) The state of the art in themanagement of inflammatory bowel disease. Rev Gastroenterol Dis 3:81–92

    Google Scholar 

  • Hanauer SB, Sandborn WJ, Rutgeerts P, et al. (2006) Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I Trial. Gastroenterology 130:323–333

    Article  PubMed  CAS  Google Scholar 

  • Hommes DW, Mikhajlova TL, Stoinov S, et al. (2006) Fontolizumab, a humanized anti-interferon-gamma antibody, demonstrates safety and potential clinical activity in patients with moderate-to-severe Crohn’s disease. Gut 0: gut.2005.079392v1 [Epub ahead of print]

    Google Scholar 

  • Hugot JP, Chamailard M, Zouali H, et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411:599–603

    Article  PubMed  CAS  Google Scholar 

  • Humira [prescribing information] (2005) Abbott Laboratories, North Chicago, IL

    Google Scholar 

  • Hyams J, Crandall W, Kugathasan S, et al. (2006) Maintenance therapy with infliximab every 8 weeks is superior to every 12 weeks in maintaining response and remission in pediatric patients with moderately to severely active Crohn’s disease [abstract 57]. Presented at Digestive Disease Week 2006, Los Angeles, California, May 21, 2006

    Google Scholar 

  • Ito H, Takazoe M, Fukuda Y, et al. (2004) A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn’s disease. Gastroenterology 126: 989–996

    Article  PubMed  CAS  Google Scholar 

  • Jarnerot G, Hertevig E, Friis-Liby I, et al. (2005) Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology 128:1805–1811

    Article  PubMed  CAS  Google Scholar 

  • Jerne NK (1974) Towards a network theory of the immune system. Ann d’Immunologie 125C:373–389

    CAS  Google Scholar 

  • Kobayashi KS, Chamaillard M, Ogura Y, et al. (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307:731–734

    Article  PubMed  CAS  Google Scholar 

  • Korzenik JR, Podolsky DK (2006) Evolving knowledge and therapy of inflammatory bowel disease. Nat Rev Drug Discov 5:197–209

    Article  PubMed  CAS  Google Scholar 

  • Korzenik JR, Dieckgraefe BK, Valentine JF, et al., for the Sargramostim in Crohn’s Disease Study Group (2005) Sargramostim for active Crohn’s disease. N Engl J Med 352:2193–2201

    Article  PubMed  CAS  Google Scholar 

  • Lakatos PL, Fischer S, Lakatos L, et al. (2006) Current concept on the pathogenesis of inflammatory bowel disease — crosstalk between genetic and microbial factors: pathogenic bacteria and altered bacterial sensing or changes in mucosal integrity take “toll”? World J Gastroenterol 12:1829–1841

    PubMed  CAS  Google Scholar 

  • Maini RN, Breedveld FC, Kalden JR, et al. (1998) Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 41:1552–1563

    Article  PubMed  CAS  Google Scholar 

  • Mannon PJ, Fuss IJ, Mayer L, et al; Anti-IL-12 Crohn’s Disease Study Group (2004) Anti-interleukin-12 antibody for active Crohn’s disease. N Engl J Med 351:2069–2079

    Article  PubMed  CAS  Google Scholar 

  • Miner P, Wedel M, Bane B, et al. (2004) An enema formulation of alicaforsen, an antisense inhibitor of intercellular adhesion molecule-1, in chronic intermitting pouchitis. Aliment Pharmacol Ther 19:281–286

    Article  PubMed  CAS  Google Scholar 

  • Mitoma H, Horiuchi T, Hatta N, et al. (2005) Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-[945]. Gastroenterology 128:376–392

    Article  PubMed  CAS  Google Scholar 

  • Murch SH, Braegger CP, Walker-Smith JA, MacDonald TT (1993) Location of tumour necrosis factor alpha by immunohistochemistry in chronic inflammatory bowel disease. Gut 34:1705–1709

    PubMed  CAS  Google Scholar 

  • Murch SH, Lamkin VA, Savage MO, et al. (1991) Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease. Gut 32:913–917

    PubMed  CAS  Google Scholar 

  • Musch E, Andus R, Malek M (2002) Induction and maintenance of clinical remission by interferon beta in patients with steroid-refractory active ulcerative colitis — an open long-term pilot trial. Aliment Pharmacol Ther 16:1233–1239

    Article  PubMed  CAS  Google Scholar 

  • Nayar M, Rhodes JM (2004) Management of inflammatory bowel disease. Postgrad Med J 80:206–213

    Article  PubMed  CAS  Google Scholar 

  • Nikolaus S, Rutgeerts P, Fedorak R, et al. (2003) Interferon beta-1a in ulcerative colitis: a placebo controlled, randomized, dose escalating study. Gut 52:1286–1290

    Article  PubMed  CAS  Google Scholar 

  • Noble C, Nimmo E, Gaya D, et al. (2006) Novel susceptibility genes in inflammatory bowel disease. World J Gastroenterol 12:1991–1999

    PubMed  CAS  Google Scholar 

  • Ogura Y, Bonen DK, Inohara N, et al. (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411:603–606

    Article  PubMed  CAS  Google Scholar 

  • Papadakis KA, Shaye OA, Vasiliauskas EA, et al. (2005) Safety and efficacy of adalimumab (D2E7) in Crohn’s disease patients with an attenuated response to infliximab. Am J Gastroenterol 100:75–79

    Article  PubMed  CAS  Google Scholar 

  • Peltekova VD, Wintle RF, Rubin LA, et al. (2004) Functional variants of OCTN cation transporter genes are associated with Crohn’s disease. Nat Genet 5:800–808

    Article  CAS  Google Scholar 

  • Reinisch W, Hommes DW, Van Assche G, et al. (2006) A dose-escalating, placebo-controlled, double-blind, single-dose and multi-dose, safety and tolerability study of fontolizumab, a humanized anti-interferon-gamma antibody, in patients with moderate-to-severe Crohn’s disease. Gut. Epub ahead of print. doi:10.1136/gut.2005.079434

    Google Scholar 

  • Remicade (infliximab) prescribing information (2006) Centocor, Inc. Malvern, PA, March, 2006

    Google Scholar 

  • Rutgeerts P (2002) Current dilemmas in the management of inflammatory bowel disease. Eur J Surg Suppl (587):58–61

    PubMed  Google Scholar 

  • Rutgeerts P, Feagan BG, Lichtenstein GR, et al. (2004a) Comparison of scheduled and episodic treatment strategies of infliximab in Crohn’s disease. Gastroenterology 126:402–413

    Article  PubMed  CAS  Google Scholar 

  • Rutgeerts P, Fedorak RN, Rachmilevich D, et al., for the Onercept Study Group (2004b) Onercept (recombinant human p55 tumour necrosis factor receptor) treatment in patients with active Crohn’s disease: randomized, placebo-controlled, dose-finding phase II study (abstract). Gut 53(Suppl VI):A47

    Google Scholar 

  • Rutgeerts P, Sandborn WJ, Feagan BG, et al. (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353:2462–2476

    Article  PubMed  CAS  Google Scholar 

  • Sandborn WJ, Hanauer SB, Katz S, et al. (2001) Etanercept for active Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology 121:1088–1094

    Article  PubMed  CAS  Google Scholar 

  • Sandborn WJ, Hanauer S, Loftus EV Jr, et al. (2004a) An open-label study of the human anti-TNF monoclonal antibody adalimumab in subjects with prior loss of response or intolerance to infliximab for Crohn’s disease. AmJ Gastroenterol 99:1984–1989

    Article  CAS  Google Scholar 

  • Sandborn WJ, Feagan BG, Radford-Smith G, et al. (2004b) CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn’s disease: a randomised, double-blind, placebo-controlled trial. Gut 53:1485–1493

    Article  PubMed  CAS  Google Scholar 

  • Sandborn W, Hanauer S, Lukas M, et al. (2005a) Induction and maintenance of clinical remission and response in subjects with Crohn’s disease treated during a 6-month open-label period with fully human anti-TNF-α monoclonal antibody adalimumab (Humira®). Gastroenterology 128(4 Suppl 2):A-111 (presentation 723)

    Google Scholar 

  • Sandborn WJ, Hanauer S, Enns R, et al. (2005b) Maintenance of remission over 1 year in patients with active Crohn’s disease treated with adalimumab: results of CLASSIC II, a blinded, placebo-controlled study. Gut 54(SupplVII):A81–2 (oral presentation OP-G-353)

    Google Scholar 

  • Sandborn WJ, Hanauer S, Lukas M, et al. (2005c) Clinical remission and response in patients with Crohn’s disease treated with open-label for 1 year with fully human anti-TNF-α monoclonal antibody adalimumab. Gut 54(Suppl VII):A18 (oral presentation OP-G-78)

    Google Scholar 

  • Sandborn WJ, Colombel JF, Enns R, et al., for the International Efficacy of Natalizumab as Active Crohn’s Therapy ENACT-1 Trial Group and the Evaluation of Natalizumab as Continuous Therapy ENACT-2 Trial Group (2005d) Natalizumab induction and maintenance therapy for Crohn’s disease. N Engl J Med 353:1912–1925

    Article  PubMed  CAS  Google Scholar 

  • Sandborn WJ, Feagan BG, Stoinov S, et al. (2006) Certolizumab pegol administered subcutaneously is effective and well tolerated in patients with active Crohn’s disease: results from a 26-week, placebo-controlled phase III study (PRECiSE 1). Presented at Digestive Disease Week 2006, Los Angeles, California, May 23, 2006

    Google Scholar 

  • Sands BE, Anderson FH, Bernstein CN, et al. (2004) Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 350:876–885

    Article  PubMed  CAS  Google Scholar 

  • Scallon BJ, Moore MA, Trinh H, et al. (1995) Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine 7:251–259

    Article  PubMed  CAS  Google Scholar 

  • Schmidt C, Giese T, Ludwig B, Mueller-Molaian I, et al. (2005) Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn’s disease but not in ulcerative colitis. Inflamm Bowel Dis 11:16–23

    Article  PubMed  Google Scholar 

  • Schreiber S (2005) Certolizumab pegol, a humanised anti-tnf pegylated fab’ fragment, is safe and effective in the maintenance of response and remission following induction in active Crohn’s disease: a phase III study (PRECiSE). Presented at the 13th United European Gastroenterology Week, Copenhagen, Denmark, October 18, 2005

    Google Scholar 

  • Schreiber S (2006) Slipping the barrier: how variants in CARD15 could alter permeability of the intestinal wall and population health. Gut 55:308–309

    Article  PubMed  CAS  Google Scholar 

  • Schreiber S, Rutgeerts P, Fedorak RN, et al.; CDP870 Crohn’s Disease Study Group (2005) A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn’s disease. Gastroenterology 129:807–818

    Article  PubMed  CAS  Google Scholar 

  • Shen C, Assche GV, Colpaert S, et al. (2005) Adalimumab induces apoptosis of human monocytes: a comparative study with infliximab and etanercept. Aliment Pharmacol Ther 21:251–258

    Article  PubMed  CAS  Google Scholar 

  • Slonim AE, Bulone L, Damore MB, et al. (2000) A preliminary study of growth hormone therapy for Crohn’s disease. N Engl J Med 342:1633–1637

    Article  PubMed  CAS  Google Scholar 

  • Stallmach A, Giese T, Schmidt C, et al. (2004) Severe anaphylactic reaction to infliximab: successful treatment with adalimumab — report of a case. Eur J Gastroenterol Hepatol 16:627–630

    Article  PubMed  CAS  Google Scholar 

  • Stoll M, Corneliussen B, Costello CM, et al. (2004) Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat Genet 36:476–480

    Article  PubMed  CAS  Google Scholar 

  • Targan SR, Hanauer SB, van Deventer SJ, et al., for the Crohn’s Disease cA2 Study Group (1997) A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. N Engl J Med 337:1029–1035

    Article  PubMed  CAS  Google Scholar 

  • Van Assche G, Vermeire S, Rutgeerts P (2005) Medical treatment of inflammatory bowel diseases. Curr Opin Gastroenterol 21:443–447

    PubMed  Google Scholar 

  • van den Brande JM, Braat H, van den Brink GR, et al. (2003) Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn’s disease. Gastroenterology 124:1774–1785

    Article  PubMed  CAS  Google Scholar 

  • van Deventer SJ (2003) New biological therapies in inflammatory bowel disease. Best Pract Res Clin Gastroenterol 17: 119–130

    Article  PubMed  CAS  Google Scholar 

  • van Deventer SJ, Tami JA, Wedel MK, et al. (2004) An enema formulation of alicaforsen, an antisense inhibitor of intercellular adhesion molecule-1 in active ulcerative colitis. Gut 53:1646–1651

    Article  PubMed  CAS  Google Scholar 

  • Vermeire S, Rutgeerts P (2006) The changing face of treatment for Crohn’s disease. Br J Surg 93:385–386

    Article  PubMed  CAS  Google Scholar 

  • Wehkamp J, Harder J, Weichenthal M, et al. (2004) NOD2 (CARD15) mutations in Crohn’s disease are associated with diminished mucosal alpha-defensin expression. Gut 53: 1658–1664

    Article  PubMed  CAS  Google Scholar 

  • Youdim A, Vasikiauskas EA, Targan SR, et al. (2004) A pilot study of adalimumab in infliximab-allergic patients. Inflamm Bowel Dis 10:333–338

    Article  PubMed  Google Scholar 

  • Zhou H, Buckwalter M, Boni J, et al. (2004) Population-based pharmacokinetics of the soluble TNFr etanercept: a clinical study in 43 patients with ankylosing spondylitis compared with post hoc data from patients with rheumatoid arthritis. Int J Clin Pharmacol Ther 42:267–276

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Salfeld, J., Rutgeerts, P. (2007). Biologics in Crohn’s Disease and Ulcerative Colitis: Focus on Tumor Necrosis Factor Antagonists. In: Boehncke, WH., Radeke, H.H. (eds) Biologics in General Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-29018-6_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-29018-6_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-29017-9

  • Online ISBN: 978-3-540-29018-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics