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Vol. 30, Suppl. 3, 2012
Issue release date: January 2013
Dig Dis 2012;30(suppl 3):121–133

Biological Treatment of Crohn’s Disease

Nielsen O.H. · Bjerrum J.T. · Seidelin J.B. · Nyberg C. · Ainsworth M.
Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

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Introduction of biological agents for the treatment of Crohn’s disease (CD) has led to a transformation of the treatment paradigm. Several biological compounds have been approved for patients with CD refractory to conventional treatment: infliximab, adalimumab and certolizumab pegol (and natalizumab in several countries outside the European Union). However, despite the use of biologics for more than a decade, questions still remain about the true efficacy and the best treatment regimens – especially about when to discontinue treatment. Furthermore, a need for optimizing treatment with biologics still exists, as 20–40% of patients with CD (depending on selection criteria) do not have any relevant response to the current biological agents (i.e. primary failures). A better patient selection might maximize the clinical outcome while minimizing the complications associated with this type of therapy. However, the clinical tools capable of identifying such patients are still unavailable, and the trough level strategy may help the clinician to optimize therapy and to avoid loss of response and/or immunogenicity (i.e. a low but measurable antibody level exists just before the periodic administration of the biological agent). On the other hand, peak levels and average levels should not exceed concentrations associated with increased toxicity. Randomized, controlled studies focusing on trough levels and antibodies towards the biological agent in routine clinical situations may add important pieces to the puzzle for a more rational treatment algorithm of CD patients. In some situations, the risks (i.e. immunogenicity, serious infections and the promotion of neoplasia) may, however, not outweigh the benefits of biological treatment.

Copyright / Drug Dosage

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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. Ordas I, Feagan BG, Sandborn WJ: Early use of immunosuppressives or TNF antagonists for the treatment of Crohn’s disease: time for a change. Gut 2011;60:1754–1763.
  2. Ford AC, Sandborn WJ, Khan KJ, Hanauer SB, Talley NJ, Moayyedi P: Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol 2011;106:644–659.
  3. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P: Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002;359:1541–1549.
  4. Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T, DeWoody KL, Schaible TF, Rutgeerts PJ: A short-term 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.
  5. Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh D, Panaccione R, Wolf D, Pollack P: Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology 2006;130:323–333.
  6. Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Colombel JF, Panaccione R, D’Haens G, Li J, Rosenfeld MR, Kent JD, Pollack PF: Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med 2007;146:829–838.
  7. Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, Bloomfield R, Schreiber S: Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med 2007;357:228–238.
  8. Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OO, Hanauer SB, McColm J, Bloomfield R, Sandborn WJ: Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med 2007;357:239–250.
  9. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, Podolsky DK, Sands BE, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ: Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999;340:1398–1405.
  10. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ: Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004;350:876–885.
  11. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D’Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P: Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 2010;362:1383–1395.
  12. D’Haens G, Baert F, van AG, Caenepeel P, Vergauwe P, Tuynman H, De VM, van DS, Stitt L, Donner A, Vermeire S, Van de Mierop FJ, Coche JC, van der WJ, Ochsenkuhn T, van Bodegraven AA, Van Hootegem PP, Lambrecht GL, Mana F, Rutgeerts P, Feagan BG, Hommes D: Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet 2008;371:660–667.
  13. Feagan B, McDonald JW, Panaccione R, Enns RA, Bernstein CN, Ponich TP, Greenberg GR: A randomized trial of methotrexate in combination with infliximab for the treatment of Crohn’s disease. Gastroenterology 2008;135:294–295.

    External Resources

  14. Lemann M, Mary JY, Duclos B, Veyrac M, Dupas JL, Delchier JC, Laharie D, Moreau J, Cadiot G, Picon L, Bourreille A, Sobahni I, Colombel JF: Infliximab plus azathioprine for steroid-dependent Crohn’s disease patients: a randomized placebo-controlled trial. Gastroenterology 2006;130:1054–1061.
  15. Sokol H, Seksik P, Carrat F, Nion-Larmurier I, Vienne A, Beaugerie L, Cosnes J: Usefulness of co-treatment with immunomodulators in patients with inflammatory bowel disease treated with scheduled infliximab maintenance therapy. Gut 2010;59:1363–1368.
  16. Nielsen OH, Seidelin JB, Munck LK, Rogler G: Use of biological molecules in the treatment of inflammatory bowel disease. J Intern Med 2011;270:15–28.
  17. Regueiro M, Schraut W, Baidoo L, Kip KE, Sepulveda AR, Pesci M, Harrison J, Plevy SE: Infliximab prevents Crohn’s disease recurrence after ileal resection. Gastroenterology 2009;136:441–450.
  18. De Cruz P, Kamm MA, Hamilton AI, Ritchie KJ, Gorelik A, Liew D, Lawrence IC, Desmond P: Adalimumab prevents post-operative Crohn’s disease recurrence, and is superior to thiopurines. Early results from the POCER study. Gastroenterology 2012;142(suppl 5):S-212.
  19. Cosnes J, Carbonnel F, Beaugerie L, Le QY, Gendre JP: Effects of cigarette smoking on the long-term course of Crohn’s disease. Gastroenterology 1996;110:424–431.
  20. Mahid SS, Minor KS, Soto RE, Hornung CA, Galandiuk S: Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clin Proc 2006;81:1462–1471.
  21. Reese GE, Nanidis T, Borysiewicz C, Yamamoto T, Orchard T, Tekkis PP: The effect of smoking after surgery for Crohn’s disease: a meta-analysis of observational studies. Int J Colorectal Dis 2008;23:1213–1221.
  22. Johnson GJ, Cosnes J, Mansfield JC: Review article: smoking cessation as primary therapy to modify the course of Crohn’s disease. Aliment Pharmacol Ther 2005;21:921–931.
  23. Cosnes J, Beaugerie L, Carbonnel F, Gendre JP: Smoking cessation and the course of Crohn’s disease: an intervention study. Gastroenterology 2001;120:1093–1099.
  24. Nielsen OH, Bjerrum JT, Csillag C, Nielsen FC, Olsen J: Influence of smoking on colonic gene expression profile in Crohn’s disease. PLoS One 2009;4:e6210.
  25. Parsi MA: Does smoking decrease the response to infliximab in patients with Crohn’s disease? Inflamm Bowel Dis 2008;14(suppl 2):S18–S19.
  26. Larsen S, Bendtzen K, Nielsen OH: Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann Med 2010;42:97–114.
  27. Bernstein M, Irwin S, Greenberg GR: Maintenance infliximab treatment is associated with improved bone mineral density in Crohn’s disease. Am J Gastroenterol 2005;100:2031–2035.
  28. Miheller P, Muzes G, Racz K, Blazovits A, Lakatos P, Herszenyi L, Tulassay Z: Changes of OPG and RANKL concentrations in Crohn’s disease after infliximab therapy. Inflamm Bowel Dis 2007;13:1379–1384.
  29. Machado P, Landewe R, Lie E, Kvien TK, Braun J, Baker D, van der HD: Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores. Ann Rheum Dis 2011;70:47–53.
  30. Rebelo A, Leite S, Cotter J: Association of ankylosing spondylitis and Crohn’s disease successfully treated with infliximab. Bio Drugs 2010;24(suppl 1):37–39.
  31. Quin A, Kane S, Ulitsky O: A case of fistulizing Crohn’s disease and erythema nodosum managed with adalimumab. Nat Clin Pract Gastroenterol Hepatol 2008;5:278–281.
  32. Mooij JE, van R, Mekkes JR: Six patients with pyoderma gangrenosum successfully treated with infliximab. Int J Dermatol 2012, E-pub ahead of print.
  33. Karamlou K, Gorn AH: Refractory sweet syndrome with autoimmune organizing pneumonia treated with monoclonal antibodies to tumor necrosis factor. J Clin Rheumatol 2004;10:331–335.
  34. Diaz-Llopis M, Salom D, Garcia-de-Vicuna C, Cordero-Coma M, Ortega G, Ortego N, Suarez-de-Figueroa M, Rio-Pardo MJ, Fernandez-Cid C, Fonollosa A, Blanco R, Garcia-Aparicio AM, itez-Del-Castillo JM, Olea JL, Arevalo JF: Treatment of refractory uveitis with adalimumab: a prospective multicenter study of 131 patients. Ophthalmology 2012;119:1575–1581.
  35. Balkwill F: Tumour necrosis factor and cancer. Nat Rev Cancer 2009;9:361–371.
  36. Ding T, Ledingham J, Luqmani R, Westlake S, Hyrich K, Lunt M, Kiely P, Bukhari M, Abernethy R, Bosworth A, Ostor A, Gadsby K, McKenna F, Finney D, Dixey J, Deighton C: BSR and BHPR rheumatoid arthritis guidelines on safety of anti-TNF therapies. Rheumatology (Oxford) 2010;49:2217–2219.
  37. Dixon WG, Watson KD, Lunt M, Mercer LK, Hyrich KL, Symmons DP: Influence of anti-tumor necrosis factor therapy on cancer incidence in patients with rheumatoid arthritis who have had a prior malignancy: results from the British Society for Rheumatology Biologics Register. Arthritis Care Res (Hoboken) 2010;62:755–763.
  38. Pham T, Bachelez H, Berthelot JM, Blacher J, Bouhnik Y, Claudepierre P, Constantin A, Fautrel B, Gaudin P, Goeb V, Gossec L, Goupille P, Guillaume-Czitrom S, Hachulla E, Huet I, Jullien D, Launay O, Lemann M, Maillefert JF, Marolleau JP, Martinez V, Masson C, Morel J, Mouthon L, Pol S, Puechal X, Richette P, Saraux A, Schaeverbeke T, Soubrier M, Sudre A, Tran TA, Viguier M, Vittecoq O, Wendling D, Mariette X, Sibilia J: TNF alpha antagonist therapy and safety monitoring. Joint Bone Spine 2011;78(suppl 1):15–185.
  39. van Assche G, Lewis JD, Lichtenstein GR, Loftus EV, Ouyang Q, Panes J, Siegel CA, Sandborn WJ, Travis SP, Colombel JF: The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organisation: safety. Am J Gastroenterol 2011;106:1594–1602.
  40. Tubach F, Salmon D, Ravaud P, Allanore Y, Goupille P, Breban M, Pallot-Prades B, Pouplin S, Sacchi A, Chichemanian RM, Bretagne S, Emilie D, Lemann M, Lortholary O, Mariette X: Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: the three-year prospective French Research Axed on Tolerance of Biotherapies registry. Arthritis Rheum 2009;60:1884–1894.
  41. Aberra FN: Comparison of interferon-gamma release assay versus tuberculin skin test for tuberculosis screening in inflammatory bowel disease. Gastroenterology 2009;136:1453–1455.
  42. Wallis RS: Biologics and infections: lessons from tumor necrosis factor blocking agents. Infect Dis Clin North Am 2011;25:895–910.
  43. Gisbert JP, Chaparro M, Esteve M: Review article: prevention and management of hepatitis B and C infection in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2011;33:619–633.
  44. Brunasso AM, Puntoni M, Gulia A, Massone C: Safety of anti-tumour necrosis factor agents in patients with chronic hepatitis C infection: a systematic review. Rheumatology (Oxford) 2011;50:1700–1711.
  45. Beltran B, Nos P, Bastida G, Iborra M, Hoyos M, Ponce J: Safe and effective application of anti-TNF-alpha in a patient infected with HIV and concomitant Crohn’s disease. Gut 2006;55:1670–1671.
  46. Fiorino G, Peyrin-Biroulet L, Naccarato P, Szabo H, Sociale OR, Vetrano S, Fries W, Montanelli A, Repici A, Malesci A, Danese S: Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis 2012;18:1042–1047.
  47. Harpaz R, Ortega-Sanchez IR, Seward JF: Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008;57:1–30.

    External Resources

  48. Rahier JF, Yazdanpanah Y, Colombel JF, Travis S: The European (ECCO) Consensus on Infection in IBD: what does it change for the clinician? Gut 2009;58:1313–1315.
  49. Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, Mitton S, Orchard T, Rutter M, Younge L, Lees C, Ho GT, Satsangi J, Bloom S: Guidelines for the management of inflammatory bowel disease in adults. Gut 2011;60:571–607.
  50. Gisbert JP, Menchen L, Garcia-Sanchez V, Marin I, Villagrasa JR, Chaparro M: Comparison of the effectiveness of two protocols for vaccination (standard and double dosage) against hepatitis B virus in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2012;35:1379–1385.
  51. Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT: Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the Anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 2003;107:3133–3140.
  52. Lees CW, Ali AI, Thompson AI, Ho GT, Forsythe RO, Marquez L, Cochrane CJ, Aitken S, Fennell J, Rogers P, Shand AG, Penman ID, Palmer KR, Wilson DC, Arnott ID, Satsangi J: The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up. Aliment Pharmacol Ther 2009;29:286–297.
  53. Grijalva CG, Chen L, Delzell E, Baddley JW, Beukelman T, Winthrop KL, Griffin MR, Herrinton LJ, Liu L, Ouellet-Hellstrom R, Patkar NM, Solomon DH, Lewis JD, Xie F, Saag KG, Curtis JR: Initiation of tumor necrosis factor-alpha antagonists and the risk of hospitalization for infection in patients with autoimmune diseases. JAMA 2011;306:2331–2339.
  54. Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Chen DM, Pritchard ML, Sandborn WJ: Serious infections and mortality in association with therapies for Crohn’s disease: TREAT registry. Clin Gastroenterol Hepatol 2006;4:621–630.
  55. Lichtenstein GR, Rutgeerts P, Sandborn WJ, Sands BE, Diamond RH, Blank M, Montello J, Tang L, Cornillie F, Colombel JF: A pooled analysis of infections, malignancy, and mortality in infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease. Am J Gastroenterol 2012;107: 1051–1063.
  56. Schneeweiss S, Korzenik J, Solomon DH, Canning C, Lee J, Bressler B: Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections. Aliment Pharmacol Ther 2009;30:253–264.
  57. Kelesidis T, Salhotra A, Fleisher J, Uslan DZ: Listeria endocarditis in a patient with psoriatic arthritis on infliximab: are biologic agents as treatment for inflammatory arthritis increasing the incidence of Listeria infections? J Infect 2010;60:386–396.
  58. Bakleh M, Tleyjeh I, Matteson EL, Osmon DR, Berbari EF: Infectious complications of tumor necrosis factor-alpha antagonists. Int J Dermatol 2005;44:443–448.
  59. Shale MJ, Seow CH, Coffin CS, Kaplan GG, Panaccione R, Ghosh S: Review article: chronic viral infection in the anti-tumour necrosis factor therapy era in inflammatory bowel disease. Aliment Pharmacol Ther 2010;31:20–34.
  60. Beaugerie L, Brousse N, Bouvier AM, Colombel JF, Lemann M, Cosnes J, Hebuterne X, Cortot A, Bouhnik Y, Gendre JP, Simon T, Maynadie M, Hermine O, Faivre J, Carrat F: Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 2009;374:1617–1625.
  61. Biancone L, Petruzziello C, Orlando A, Kohn A, Ardizzone S, Daperno M, Angelucci E, Castiglione F, D’Inca R, Zorzi F, Papi C, Meucci G, Riegler G, Sica G, Rizzello F, Mocciaro F, Onali S, Calabrese E, Cottone M, Pallone F: Cancer in Crohn’s disease patients treated with infliximab: a long-term multicenter matched pair study. Inflamm Bowel Dis 2011;17:758–766.
  62. Herrinton LJ, Liu L, Weng X, Lewis JD, Hutfless S, Allison JE: Role of thiopurine and anti-TNF therapy in lymphoma in inflammatory bowel disease. Am J Gastroenterol 2011;106:2146–2153.
  63. Peyrin-Biroulet L, Khosrotehrani K, Carrat F, Bouvier AM, Chevaux JB, Simon T, Carbonnel F, Colombel JF, Dupas JL, Godeberge P, Hugot JP, Lemann M, Nahon S, Sabate JM, Tucat G, Beaugerie L: Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease. Gastroenterology 2011;141:1621–1628.
  64. Lichtenstein GR, Cohen PR, Feagan BG, Sandborn WJ, Salzberg B, Chen DM, Turner M, Mink D, Broussard DL, Diamond R: Safety of infliximab and other Crohn’s disease therapies: TREAT registry data with nearly 20,000 patient-years of follow-up. Gastroenterology 2007;132(suppl 2):A-178.
  65. Siegel CA, Marden SM, Persing SM, Larson RJ, Sands BE: Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn’s disease: a meta-analysis. Clin Gastroenterol Hepatol 2009;7:874–881.
  66. Kotlyar DS, Osterman MT, Diamond RH, Porter D, Blonski WC, Wasik M, Sampat S, Mendizabal M, Lin MV, Lichtenstein GR: A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2011;9:36–41.
  67. Food and Drug Administration: WARNING: Serious infections and malignancy.
  68. Steenholdt C, Svenson M, Bendtzen K, Thomsen OO, Brynskov J, Ainsworth MA: Severe infusion reactions to infliximab: aetiology, immunogenicity and risk factors in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2011;34:51–58.
  69. Lichtenstein GR, Diamond RH, Wagner CL, Fasanmade AA, Olson AD, Marano CW, Johanns J, Lang Y, Sandborn WJ: Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials. Aliment Pharmacol Ther 2009;30:210–226.
  70. Rivkin A: Certolizumab pegol for the management of Crohn’s disease in adults. Clin Ther 2009;31:1158–1176.
  71. Katz L, Gisbert JP, Manoogian B, Lin K, Steenholdt C, Mantzaris GJ, Atreja A, Ron Y, Swaminath A, Shah S, Hart A, Lakatos PL, Ellul P, Israeli E, Svendsen MN, van der Woude CJ, Katsanos KH, Yun L, Tsianos EV, Nathan T, Abreu M, Dotan I, Lashner B, Brynskov J, Terdiman JP, Higgins PD, Chaparro M, Ben-Horin S: Doubling the infliximab dose versus halving the infusion intervals in Crohn’s disease patients with loss of response. Inflamm Bowel Dis 2012.
  72. Hanauer SB, Panes J, Colombel JF, Bloomfield R, Schreiber S, Sandborn WJ: Clinical trial: impact of prior infliximab therapy on the clinical response to certolizumab pegol maintenance therapy for Crohn’s disease. Aliment Pharmacol Ther 2010;32:384–393.
  73. Afif W, Loftus EV Jr, Faubion WA, Kane SV, Bruining DH, Hanson KA, Sandborn WJ: Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol 2010;105:1133–1139.
  74. Ordas I, Mould DR, Feagan BG, Sandborn WJ: Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms. Clin Pharmacol Ther 2012;91:635–646.
  75. D’Haens GR, Panaccione R, Higgins PD, Vermeire S, Gassull M, Chowers Y, Hanauer SB, Herfarth H, Hommes DW, Kamm M, Lofberg R, Quary A, Sands B, Sood A, Watermayer G, Lashner B, Lemann M, Plevy S, Reinisch W, Schreiber S, Siegel C, Targan S, Watanabe M, Feagan B, Sandborn WJ, Colombel JF, Travis S: The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response? Am J Gastroenterol 2011;106:199–212.
  76. Bendtzen K, Ainsworth M, Steenholdt C, Thomsen OO, Brynskov J: Individual medicine in inflammatory bowel disease: monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies. Scand J Gastroenterol 2009;44:774–781.
  77. Steenholdt C, Svenson M, Ainsworth MA, Thomsen OO, Brynskov J, Bendtzen K: Comparison of techniques for monitoring infliximab bioavailability and immunogenicity in Crohn’s disease. Gastroenterology 2012;142(suppl 1):S-781.
  78. Baert F, Noman M, Vermeire S, van Assche G, D’Haens G, Carbonez A, Rutgeerts P: Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med 2003;348:601–608.
  79. Rutgeerts P, Vermeire S, van Assche G: Predicting the response to infliximab from trough serum levels. Gut 2010;59:7–8.
  80. Steenholdt C, Bendtzen K, Brynskov J, Thomsen OO, Ainsworth MA: Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn’s disease. Scand J Gastroenterol 2011;46:310–318.
  81. Ainsworth MA, Bendtzen K, Brynskov J: Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn’s disease. Am J Gastroenterol 2008;103:944–948.
  82. Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, Schreiber S, Byczkowski D, Li J, Kent JD, Pollack PF: Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology 2007;132:52–65.
  83. Sandborn WJ, Colombel JF, Enns R, Feagan BG, Hanauer SB, Lawrance IC, Panaccione R, Sanders M, Schreiber S, Targan S, van DS, Goldblum R, Despain D, Hogge GS, Rutgeerts P: Natalizumab induction and maintenance therapy for Crohn’s disease. N Engl J Med 2005;353:1912–1925.
  84. Marehbian J, Arrighi HM, Hass S, Tian H, Sandborn WJ: Adverse events associated with common therapy regimens for moderate-to-severe Crohn’s disease. Am J Gastroenterol 2009;104:2524–2533.
  85. van Assche G, Magdelaine-Beuzelin C, D’Haens G, Baert F, Noman M, Vermeire S, Ternant D, Watier H, Paintaud G, Rutgeerts P: Withdrawal of immunosuppression in Crohn’s disease treated with scheduled infliximab maintenance: a randomized trial. Gastroenterology 2008;134:1861–1868.
  86. Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I, van AG, Hoffman I, Van SK, Vermeire S, Rutgeerts P: Long-term outcome of treatment with infliximab in 614 patients with Crohn’s disease: results from a single-centre cohort. Gut 2009;58:492–500.
  87. Louis E, Mary JY, Vernier-Massouille G, Grimaud JC, Bouhnik Y, Laharie D, Dupas JL, Pillant H, Picon L, Veyrac M, Flamant M, Savoye G, Jian R, Devos M, Porcher R, Paintaud G, Piver E, Colombel JF, Lemann M: Maintenance of remission among patients with Crohn’s disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology 2012;142:63–70.
  88. Mahadevan U, Cucchiara S, Hyams JS, Steinwurz F, Nuti F, Travis SP, Sandborn WJ, Colombel JF: The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organisation: pregnancy and pediatrics. Am J Gastroenterol 2011;106:214–223.
  89. Kane SV, Acquah LA: Placental transport of immunoglobulins: a clinical review for gastroenterologists who prescribe therapeutic monoclonal antibodies to women during conception and pregnancy. Am J Gastroenterol 2009;104:228–233.
  90. Simister NE: Placental transport of immunoglobulin G. Vaccine 2003;21:3365–3369.
  91. Mahadevan U, Terdiman JF, Church JA, Vasiliauskas E, Gitis A, Dubinsky MC: Infliximab levels in infants born to women with inflammatory bowel disease. Gastroenterology 2007;132(suppl 2):A-144.
  92. Vasiliauskas EA, Church JA, Silverman N, Barry M, Targan SR, Dubinsky MC: Case report: evidence for transplacental transfer of maternally administered infliximab to the newborn. Clin Gastroenterol Hepatol 2006;4:1255–1258.
  93. Mahadevan U, Miller JK, Wolf DC: Adalimumab levels detected in cord blood and infants exposed in utero. Gastroenterology 2011;140(suppl 1):S61–S62.

    External Resources

  94. Mahadevan U, Abreau MT: Certolizumab use in pregnancy: low levels detected in cord blood. Gastroenterology 2009;136(suppl 1):A-146.
  95. Katz JA, Antoni C, Keenan GF, Smith DE, Jacobs SJ, Lichtenstein GR: Outcome of pregnancy in women receiving infliximab for the treatment of Crohn’s disease and rheumatoid arthritis. Am J Gastroenterol 2004;99:2385–2392.
  96. Hudson M, Flett G, Sinclair TS, Brunt PW, Templeton A, Mowat NA: Fertility and pregnancy in inflammatory bowel disease. Int J Gynaecol Obstet 1997;58:229–237.
  97. Lichtenstein GR, Cohen RD, Feagan BG, Sandborn WJ, Salzberg BA, Chen DM, Diamond RH: Safety of infliximab in Crohn’s disease: data from the 5,000-patient TREAT registry. Gastroenterology 2004;126(suppl 1):A-54.
  98. Schnitzler F, Fidder H, Ferrante M, Ballet V, Noman M, van AG, Spitz B, Hoffman I, Van SK, Vermeire S, Rutgeerts P: Outcome of pregnancy in women with inflammatory bowel disease treated with antitumor necrosis factor therapy. Inflamm Bowel Dis 2011;17:1846–1854.
  99. Mahadevan U, Martin CF, Sandler RS, Kane SV, Dubinsky M, Lewis JD, Sandborn WJ, Sands B: PIANO: A 1,000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy. Gastroenterology 2012;142(suppl 1):S-149.
  100. Peltier M, James D, Ford J, Wagner C, Davis H, Hanauer S: Infliximab levels in breast-milk of a nursing Crohn’s patient. Am J Gastroenterol 2001;96(suppl 1):S312.

    External Resources

  101. Ben-Horin S, Yavzori M, Kopylov U, Picard O, Fudim E, Eliakim R, Chowers Y, Lang A: Detection of infliximab in breast milk of nursing mothers with inflammatory bowel disease. J Crohns Colitis 2011;5:555–558.
  102. Kane S, Ford J, Cohen R, Wagner C: Absence of infliximab in infants and breast milk from nursing mothers receiving therapy for Crohn’s disease before and after delivery. J Clin Gastroenterol 2009;43:613–616.
  103. Ben-Horin S, Yavzori M, Katz L, Picard O, Fudim E, Chowers Y, Lang A: Adalimumab level in breast milk of a nursing mother. Clin Gastroenterol Hepatol 2010;8:475–476.
  104. Cheent K, Nolan J, Shariq S, Kiho L, Pal A, Arnold J: Case report: fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn’s disease. J Crohns Colitis 2010;4:603–605.
  105. Marchioni RM, Blonski W, Lichtenstein GR: Anti-TNF inhibitor therapy and fetal risk: a systematic literature review. Gastroenterology 2012;142(suppl 1):S-248.
  106. Paschou S, Voulgari PV, Vrabie IG, Saougou IG, Drosos AA: Fertility and reproduction in male patients with ankylosing spondylitis treated with infliximab. J Rheumatol 2009;36:351–354.
  107. Sato A, Naganuma M, Asakura K, Nishiwaki Y, Yajima T, Hisamatsu T, Iwao Y, Takebayashi T, Watanabe M, Hibi T: Conception outcomes and opinions about pregnancy for men with inflammatory bowel disease. J Crohns Colitis 2010;4:183–188.
  108. Mahadevan U, Terdiman JP, Aron J, Jacobsohn S, Turek P: Infliximab and semen quality in men with inflammatory bowel disease. Inflamm Bowel Dis 2005;11:395–399.
  109. Plevy SE, Targan SR: Future therapeutic approaches for inflammatory bowel diseases. Gastroenterology 2011;140:1838–1846.

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