Gastroenterology
Volume 133, Issue 1 , Pages 312-339 , July 2007

American Gastroenterological Association Consensus Development Conference on the Use of Biologics in the Treatment of Inflammatory Bowel Disease, June 21–23, 2006

  • Michael Clark

      Affiliations

    • Department of Pathology, Cambridge University, Cambridge, England
  • ,
  • Jean-Frederic Colombel

      Affiliations

    • Clin Des Maladies De L Apparei, Hopital Huriez Chru, Lille, France
  • ,
  • Brian C. Feagan

      Affiliations

    • Robarts Clinical Trials, London, England
  • ,
  • Richard N. Fedorak

      Affiliations

    • Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
  • ,
  • Stephen B. Hanauer

      Affiliations

    • Medicine/Gastroenterology & Nutrition, The University of Chicago, Chicago, Illinois
    • Corresponding Author InformationAddress requests for reprints to: Stephen B. Hanauer, MD, and Paul Rutgeerts, MD, C/O of the AGA Institute National Office, 4930 Del Ray Avenue, Bethesda, Maryland 20814. Fax: (301) 654-5920.
  • ,
  • Michael A. Kamm

      Affiliations

    • St. Mark’s Hospital, Harrow, England
  • ,
  • Lloyd Mayer

      Affiliations

    • Center for Immunology, Mount Sinai Medical Center, New York, New York
  • ,
  • Carol Regueiro

      Affiliations

    • Freelance Medical Writer, Pittsburgh, Pennsylvania
  • ,
  • Paul Rutgeerts

      Affiliations

    • University Hospital Gasthuisberg, Leuven, Belgium
  • ,
  • William J. Sandborn

      Affiliations

    • IBD Interest Group, Mayo Clinic, Gastroenterology and Hepatology, Rochester, Minnesota
  • ,
  • Bruce E. Sands

      Affiliations

    • Clinical Research, Massachusetts General Hospital, Andover, Massachusetts
  • ,
  • Stefan Schreiber

      Affiliations

    • Department of General Internal Medicine, Christian-Albrechts-University, Kiel, Germany
  • ,
  • Stephan Targan

      Affiliations

    • Division of Gastroenterology & IBD Center, Cedars-Sinai Medical Center, Los Angeles, California
  • ,
  • Simon Travis

      Affiliations

    • John Radcliffe Hospital, Gastroenterology Unit, Oxford, England
  • ,
  • Severine Vermeire

      Affiliations

    • University Hospital Gasthuisberg, Leuven, Belgium

References 

  1. Centre for Evidence Based Medicine. Levels of evidence and grades of recommendation. Available at: http://www.cebm.net/levels_of_evidence.asp#levels. Accessed August 3, 2006.
  2. Sands BE, Arsenault JE, Rosen MJ, Alsahli M, Bailen L, Banks P, et al. Risk of early surgery for Crohn’s disease: implications for early treatment strategies. Am J Gastroenterol. 2003;98:2712–2718
  3. Wolters FL, Russel MG, Stockbrugger RW. Systematic review: has disease outcome in Crohn’s disease changed during the last four decades?. Aliment Pharmacol Ther. 2004;20:483–496
  4. Gregor JC, McDonald JW, Klar N. An evaluation of utility measurement in Crohn’s disease. Inflamm Bowel Dis. 1997;3:265–276
  5. 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
  6. United States Food and Drug Administration. About the Center for Biologics Evaluation and Research (CBER). 2005;Available at: http://www.fda.gov/cber/about.htm. December 30. Accessed December 28, 2006.
  7. Scallon BJ, Moore MA, Trinh H, Knight DM, Ghrayeb J. Chimeric anti-TNF monoclonal effector functions. Cytokine. 1995;7:251–259
  8. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52:3381–3390
  9. Hommes D, Baert F, van Assche G, et al. Management of recent onset Crohn’s disease: a controlled, randomized trial comparing step-up and top-down therapy (abstr). Gastroenterology. 2005;129:370
  10. U.S. Food and Drug Administration. Center for Drug Evaluation and Research. Questions and answers on Remicade/FDA action. 2006;May 19. Available at: http://www.fda.gov/cder/drug/infopage/infliximab/qa.htm. Accessed August 1, 2006.
  11. Tysabri (natalizumab) full prescribing information. Available at: http://www.tysabri.com/TYSABRI-pi.pdf. Accessed August 3, 2006.
  12. Hanauer SB, Sandborn WJ Practice Parameters Committee of the American College of Gastroenterology. Management of Crohn’s disease in adults. Am J Gastroenterol. 2001;96:635–643
  13. Van den Brande JM, Bratt H, van den Brink GR, Versteeg HH, Bauer CA, Hoedemaeker I, et al. Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn’s disease. Gastroenterology. 2003;124:1774–1785
  14. Targan SR, Hanauer SB, van Deventer SJH, Mayer L, Present DH, Braakman T, 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;337:1029–1035
  15. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–1549
  16. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999;340:1398–1405
  17. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350:876–885
  18. Sands BE, Blank MA, Patel K, van Deventer SJ. ACCENT II Study. Long-term treatment of rectovaginal fistulas in Crohn’s disease: response to infliximab in the ACCENT II Study. Clin Gastroenterol Hepatol. 2004;2:912–920
  19. Hyams JS, 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
  20. Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476
  21. Jarnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlen P, Granno C, et al. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005;128:1805–1811
  22. Herfarth H, Obermeier F, Andus T, Rogler G, Nikolaus S, Kuehbacher T, et al. Improvement of arthritis and arthralgia after treatment with infliximab (Remicade) in a German prospective, open-label, multicenter trial in refractory Crohn’s disease. Am J Gastroenterol. 2002;97:2688–2690
  23. Generini S, Giacomelli R, Fedi R, Fulminis A, Pignone A, Frieri G, et al. Infliximab in spondyloarthropathy associated with Crohn’s disease: an open study on the efficacy of inducing and maintaining remission of musculoskeletal and gut manifestations. Ann Rheum Dis. 2004;63:1664–1669
  24. Brooklyn TN, Dunnill MG, Shetty A, Bowden JJ, Williams JD, Griffiths CE, et al. Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut. 2006;55:505–509
  25. Fries W, Giofre MR, Catanoso M, Lo Gullo R. Treatment of acute uveitis associated with Crohn’s disease and sacroileitis with infliximab. Am J Gastroenterol. 2002;97:499–500
  26. Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh D, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006;130:323–333
  27. Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132:52–65
  28. Sandborn WJ, Rutgeerts P, Enns RA, Hanauer SB, Colombel JF, Panaccione R, et al. Adalimumab rapidly induces clinical remission and response in patients with moderate to severe Crohn’s disease who had secondary failure to infliximab therapy: results of the GAIN study (abstr). Am J Gastroenterol. 2006;101:S448
  29. Nesbitt AM, Henry AJ. High affinity and potency of the pegylated FAB’ fragment CDP870 – a direct comparison with other anti-TNF agents (abstr). Am J Gastroenterol. 2004;99:S253
  30. Fossati G, Nesbitt A. 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. 2005;100(Suppl):S298–S299
  31. Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, McColm JA, et al. Certolizumab pegol administered subcutaneously is effective and well tolerated in patients with active Crohn’s disease: results from a 26-week, placebo-controlled phase II study (PRECiSE 1) (abstr). Gastroenterology. 2006;130(Suppl 2):A-107
  32. Schreiber S, Khaliq-Kareemi M, Lawrance I, Hanauer S, McColm J, Bloomfield R, et al. Certolizumab pegol, a humanized 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) (abstr). Gut. 2005;54(Suppl VII):A82
  33. Ghosh S, Goldin E, Gordon FH, Malchow HA, Rask-Madsen J, Rutgeerts P, et al. Natalizumab for active Crohn’s disease. N Engl J Med. 2003;348:24–32
  34. Sandborn WJ, Colombel JF, Enns R, Feagan BG, Hanauer SB, Lawrance IC, et al. Natalizumab induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2005;353:1912–1925
  35. Targan SR, Feagan B, Fedorak R, Lashner B, Panacionne R, Present D, et al. Natalizumab induces sustained response and remission in patients with active Crohn’s disease: results from the Encore trial (abstr). Gastroenterology. 2006;130(Suppl 2):A108
  36. Kleinschmidt-DeMasters BK, Tyler KL. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med. 2005;353:369–374
  37. Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med. 2005;353:375–381
  38. Van Assche G, Van Ranst M, Sciot R, Dubois B, Vermeire S, Noman M, et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med. 2005;353:362–368
  39. Yousry TA, Major EO, Ryschkewitsch C, Fahle G, Fischer S, Hou J, et al. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med. 2006;354:924–933
  40. Sands BE, Kozarek R, Spainhour J, Barish CF, Becker S, Goldberg L, et al. Safety and tolerability of concurrent natalizumab treatment for patients with Crohn’s disease not in remission while receiving infliximab. Inflamm Bowel Dis. 2007;13:2–11
  41. Korzenik JR, Dieckgraefe BK, Valentine JF, Hausman DF, Gilbert MJ Sargramostim in Crohn’s Disease Study Group. Sargramostim for active Crohn’s disease. N Engl J Med. 2005;352:2193–2201
  42. Su C, Lichtenstein GR, Krok K, Brensinger CM, Lewis JD. A meta-analysis of the placebo rates of remission and response in clinical trials of active Crohn’s disease. Gastroenterology. 2004;126:1257–1269
  43. Best WR, Becktel JM, Singleton JW, Kern F. Development of a Crohn’s disease activity index (National Cooperative Crohn’s Disease Study). Gastroenterology. 1976;70:439–444
  44. Harvey RF, Bradshaw JM. A simple index of Crohn’s-disease activity. Lancet. 1980;1:514
  45. Myren J, Bouchier IA, Watkinson G, Softley A, Clamp SE, de Dombal FT. The O.M.G.E. Multinational Inflammatory Bowel Disease Survey 1976-1982. A further report on 2,657 cases. Scand J Gastroenterol Suppl. 1984;95:1–27
  46. Wright JP, Marks IN, Parfitt A. A simple clinical index of Crohn’s disease activity—the Cape Town index. S Afr Med J. 1985;68:502–503
  47. van Hees PA, van Elteren PH, van Lier HJ, van Tongeren JH. An index of inflammatory activity in patients with Crohn’s disease. Gut. 1980;21:279–286
  48. Present DH, Korelitz BI, Wisch N, Glass JL, Sachar DB, Pasternack BS. Treatment of Crohn’s disease with 6-mercaptopurine (A long-term, randomized, double-blind study). N Engl J Med. 1980;302:981–987
  49. Sands BE, Steinhart AH, Lewis JD, Hanauer SB, Persson T, Sandborn WJ. Optimal Crohn’s disease activity index (CDAI) response criteria is defined by decrease ≥ 100 points (abstr). Gastroenterology. 2003;124(Suppl):A206
  50. Sandborn WJ, Feagan BG, Hanauer SB, Lochs H, Lofberg R, Modigliani R, et al. A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with Crohn’s disease. Gastroenterology. 2002;122:512–530
  51. Will M, Nikolaus S, Freitag S, et al. Placebo response in the therapy of Crohn’s disease: a comprehensive analysis of primary data from 733 patients from 13 randomized, controlled trials. Gastroenterology. 2005;128(Suppl 2):A-48
  52. Feagan B, Rutgeerts P, Schreiber S, et al. Low baseline CRP correlates with a high placebo remission rate in Crohn’s disease (CD) clinical trial at 12 weeks. Gastroenterology. 2005;128(Suppl 2):A-307
  53. Mary JY, Modigliani R. Development and validation of an endoscopic index of the severity for Crohn’s disease: a prospective multicentre study. Groupe d’Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut. 1989;30:983–989
  54. Daperno M, D’Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al. Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc. 2004;60:505–512
  55. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990;99:956–963
  56. Cellier C, Sahmoud T, Froguel E, Adenis A, Belaiche J, Bretagne JF, et al. Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn’s disease. A prospective multicentre study of 121 cases. The Groupe d’Etudes Therapeutiques des Affections Inflammatoires Digestives. Gut. 1994;35:231–235
  57. Powell-Tuck J, Day DW, Buckell NA, Wadsworth J, Lennard-Jones JE. Correlations between defined sigmoidoscopic appearances and other measures of disease activity in ulcerative colitis. Dig Dis Sci. 1982;27:533–537
  58. Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. BMJ. 1989;298:82–86
  59. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis (A randomized study). N Engl J Med. 1987;317:1625–1629
  60. Baron JH, Connell AM, Lennard-Jones JE. Variation between observers in describing mucosal appearances in proctocolitis. BMJ. 1964;1:89–92
  61. D’Haens G, Sandborn WJ, Feagan BG, Geboes K, Hanauer SB, Irvine EJ, et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007;132:763–786
  62. Seo M, Okada M, Yao T, Matake H, Maeda K. Evaluation of the clinical course of acute attacks in patients with ulcerative colitis through the use of an activity index. J Gastroenterol. 2002;37:29–34
  63. Lindgren SC, Flood LM, Kilander AF, Lofberg R, Persson TB, Sjodahl RI. Early predictors of glucocorticoid treatment failure in severe and moderately severe attacks of ulcerative colitis. Eur J Gastroenterol Hepatol. 1998;10:831–835
  64. Travis SPL, Farrant JM, Ricketts C, Kettlewell MGW, Mortensen NJ, Jewell DP. Predicting outcome in severe ulcerative colitis. Gut. 1996;38:905–910
  65. Lionetti P, Bronzini F, Salvestrini C, Bascietto C, Canani RB, De Angelis GL, et al. Response to infliximab is related to disease duration in paediatric Crohn’s disease. Aliment Pharmacol Ther. 2003;18:425–431
  66. Kugathasan S, Werlin SL, Martinez A, Rivera MT, Heikenen JB, Binion DG. Prolonged duration of response to infliximab in early but not late pediatric Crohn’s disease. Am J Gastroenterol. 2000;95:3189–3194
  67. Schreiber S, Reinisch W, Colombel JF, Sandborn WJ, Hommes DW, Li J, et al. Early Crohn’s disease shows high levels of remission to therapy with adalimumab: sub-analysis of CHARM (abstr). Gastroenterology. 2007;132:A932
  68. Sandborn WJ, Colombel JF, Panes J, Scholmerich J, McColm JA, Schreiber S. Higher remission and maintenance of response rates with subcutaneous monthly certolizumab pegol in patients with recent-onset Crohn’s disease: data from PRECiSE 2 (abstr 1109). Am J Gastroenterol. 2006;101:S434–S435
  69. Lichtenstein GR. Treatment of Fistulizing Crohn’s disease. Gastroenterology. 2000;119:1132–1147
  70. Laharie D, Salzmann M, Boubekeur H, Richy F, Amouretti M, Quinton A, et al. Predictors of response to infliximab in luminal Crohn’s disease. Gastroenterol Clin Biol. 2005;29:145–149
  71. Arnott ID, McNeill G, Satsangi J. An analysis of factors influencing short-term and sustained response to infliximab treatment for Crohn’s disease. Aliment Pharmacol Ther. 2003;17:1451–1457
  72. Parsi MA, Achkar JP, Richardson S, Katz J, Hammel JP, Lashner BA, et al. Predictors of response to infliximab in patients with Crohn’s disease. Gastroenterology. 2002;123:707–713
  73. Maini RN, Breedveld FC, Kalden JR, Smolen JS, Davis D, Macfarlane JD, et al. 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. 1998;41:1552–1563
  74. Vermeire S, Louis E, Carbonez A, Van Assche G, Noman M, Belaiche J, et al. Demographic and clinical parameters influencing the short-term outcome of anti-tumor necrosis factor (infliximab) treatment in Crohn’s disease. Am J Gastroenterol. 2002;97:2357–2363
  75. Baert F, Noman M, Vermeire S, Van Assche G, D’ Haens G, Carbonez A, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med. 2003;348:601–608
  76. Roblin X, Serre-Debeauvais F, Phelip JM, Bessard G, Bonaz B. Drug interaction between infliximab and azathioprine in patients with Crohn’s disease. Aliment Pharmacol Ther. 2003;18:917–925
  77. Louis E, El Ghoul Z, Vermeire S, Dall’Ozzo S, Rutgeerts P, Paintaud G, et al. Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn’s disease. Aliment Pharmacol Ther. 2004;19:511–519
  78. Hlavaty T, Pierik M, Henckaerts L, Ferrante M, Joossens S, van Schuerbeek N, et al. Polymorphisms in apoptosis genes predict response to infliximab therapy in luminal and fistulizing Crohn’s disease. Aliment Pharmacol Ther. 2005;22:613–626
  79. Lugering A, Schmidt M, Lugering N, Pauels HG, Domschke W, Kucharzik T. Infliximab induces apoptosis in monocytes from patients with chronic active Crohn’s disease by using a caspase-dependent pathway. Gastroenterology. 2001;121:1145–1157
  80. ten Hove T, van Montfrans C, Peppelenbosch MP, van Deventer SJ. Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn’s disease. Gut. 2002;50:206–211
  81. Di Sabatino A, Ciccocioppo R, Cinque B, Millimaggi D, Morera R, Ricevuti L, et al. Defective mucosal T cell death is sustainably reverted by infliximab in a caspase dependent pathway in Crohn’s disease. Gut. 2004;53:70–77
  82. Taylor KD, Plevy SE, Yang H, Landers CJ, Barry MJ, Rotter JI, et al. ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn’s disease. Gastroenterology. 2001;120:1347–1355
  83. Mascheretti S, Hampe J, Croucher PJ, Nikolaus S, Andus T, Schubert S, et al. Response to infliximab treatment in Crohn’s disease is not associated with mutations in the CARD15 (NOD2) gene: an analysis in 534 patients from two multicenter, prospective GCP-level trials. Pharmacogenetics. 2002;12:509–515
  84. Pierik M, Vermeire S, Steen KV, Joossens S, Claessens G, Vlietinck R, et al. Tumour necrosis factor-alpha receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab. Aliment Pharmacol Ther. 2004;20:303–310
  85. Vermeire S, Louis E, Rutgeerts P, De Vos M, Van Gossum A, Belaiche J, et al. NOD2/CARD15 does not influence response to infliximab in Crohn’s disease. Gastroenterology. 2002;123:106–111
  86. Louis E, Vermeire S, Rutgeerts P, De Vos M, Van Gossum A, Pescatore P, et al. A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism. Scand J Gastroenterol. 2002;37:818–824
  87. Schreiber S, Rutgeerts P, Fedorak RN, Khaliq-Kareemi M, Kamm MA, Boivin M, et al. A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn’s disease. Gastroenterology. 2005;129:807–818
  88. Esters N, Vermeire S, Joossens S, Noman M, Louis E, Belaiche J, et al. Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn’s disease. Am J Gastroenterol. 2002;97:1458–1462
  89. Kavanaugh AF, Schulze-Koops H, Davis LS, Lipsky PE. Repeat treatment of rheumatoid arthritis patients with a murine anti-intercellular adhesion molecule 1 monoclonal antibody. Arthritis Rheum. 1997;40:849–853
  90. Bell S, Kamm M. Antibodies to tumour necrosis factor alpha as treatment for Crohn’s disease. Lancet. 2000;355:858–860
  91. Rutgeerts P, D’Haens G, Targan S, Vasiliauskas E, Hanauer SB, Present DH, 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
  92. Hanauer SB, Rutgeerts P, D’Haens G, et al. Delayed hypersensitivity to infliximab (Remicade) re-infusion after a 2-4 year interval without treatment (abstr). Gastroenterology. 1999;116:A731
  93. Routledge EG, Gorman SD, Clark M. Protein engineering of antibody molecules for prophylactic and therapeutic applications in man. In:  Clark M editors. Reshaping antibodies for therapy. Nottingham, England: Academic Titles; 1993;p. 13–44
  94. Clark MA. Antibody humanisation for therapeutic applications. Available at: http://www.path.cam.ac.uk/~mrc7/humanisation/. Accessed August 3, 2006.
  95. Candon S, Mosca A, Ruemmele F, Goulet O, Chatenoud L, Cezard JP. Clinical and biological consequences of immunization to infliximab in pediatric Crohn’s disease. Clin Immunol. 2006;118:11–19
  96. Elliott MJ, Maini RN, Feldmann M, Long-Fox A, Charles P, Bijl H, et al. Repeated therapy with monoclonal antibody to tumour necrosis factor alpha (CA2) in patients with rheumatoid arthritis. Lancet. 1994;344:1125–1127
  97. Rutgeerts P, Sandborn WJ, Fedorak RN, Rachmilewitz D, Tarabar D, Gibson P, et al. Onercept for moderate-to-severe Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2006;4:888–893
  98. Sandborn WJ, Hanauer SB, Katz S, Safdi M, Wolf DG, Baerg RD, et al. Etanercept for active Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology. 2001;121:1088–1094
  99. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA. 2002;287:2215–2220
  100. Begaud B, Evreux JC, Jouglard J, Lagier G. [Imputation of the unexpected or toxic effects of drugs (Actualization of the method used in France]). Therapie. 1985;40:111–118
  101. Colombel JF, Loftus EV, Tremaine WJ, Egan LJ, Harmsen WS, Schleck CD, et al. The safety profile of infliximab in patients with Crohn’s disease: the Mayo clinic experience in 500 patients. Gastroenterology. 2004;126:19–31
  102. Toruner M, Loftus EV, Colombel JF, Orenstein R, Harmsen WS, Zinsmeister AR, et al. Risk factors for opportunistic infections in inflammatory bowel disease: a case-control study (abstr). Gastroenterology. 2006;130(Suppl 2):A-71
  103. Keystone EC. Safety of biologic therapies—an update. J Rheumatol Suppl. 2005;74:8–12
  104. Ellerin T, Rubin RH, Weinblatt ME. Infections and anti-tumor necrosis factor alpha therapy. Arthritis Rheum. 2003;48:3013–3022
  105. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295:2275–2285
  106. Khanna D, McMahon M, Furst DE. Safety of tumour necrosis factor-α antagonists. Drug Saf. 2004;27:307–324
  107. Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Chen DM, et al. Serious infections and mortality in association with therapies for Crohn’s disease: TREAT registry. Clin Gastroenterol Hepatol. 2006;4:621–630
  108. Vermeire S, Noman M, Van Assche G, Baert F, Van Steen K, Esters N, et al. Autoimmunity associated with anti-tumor necrosis factor alpha treatment in Crohn’s disease: a prospective cohort study. Gastroenterology. 2003;125:32–39
  109. Sandborn WJ, Hanauer SB, Lukas M, Wolf DC, Isaacs KL, MacIntosh DG, et al. Maintenance of remission over 1 year in patients with active Crohn’s disease treated with adalimumab: results of a blinded, placebo-controlled study. Am J Gastroenterol. 2005;100(Suppl S):S311
  110. Siegel CA, Levy C, Mackenzie TA, Sands BE. Patient perceptions of the risks and benefits of infliximab for the treatment of inflammatory bowel disease (abstr). 2006;Presented at: Annual Scientific Meeting and Postgraduate Course, American College of Gastroenterology, Las Vegas, NV, October 20–25
  111. Sands B, Siegel C, Hass S, et al. Crohn’s disease patients’ willingness to accept the risks of serious adverse events in exchange for clinical benefits (abstr). 2006;Presented at Digestive Diseases Week, Los Angeles, CA, May 20–25
  112. Hanauer SB. Top-down versus step-up approaches to chronic inflammatory bowel disease: presumed innocent or presumed guilty. Nat Clin Pract Gastroenterol Hepatol. 2005;2:493
  113. Markowitz J, Hyams J, Mack D, Leleiko N, Evans J, Kugathasan S, et al. Corticosteroid therapy in the age of infliximab: acute and 1-year outcomes in newly diagnosed children with Crohn’s disease. Clin Gastroenterol Hepatol. 2006;4:1124–1129

 Participants in the conference have indicated they have the following financial relationships with companies that market drugs and devices to gastroenterologists:

Michael Clark, PhD—Consultant: BioTie Therapies Corp, BTG Plc, Cambridge University Technical Services (CUTS) Ltd, Celltech Therapeutics Ltd, Centocor, Inc

Jean-Frederic Colombel, MD—Consultant: Boehringer-Ingelheim, Otsuka Pharmaceuticals, Protein Design Labs, Gruenenthal GMBH, Pharmion, UCB Pharmaceuticals/Celltech Therapeutics Ltd, Berlex/Schering-Plough, Centocor, Inc, Schering-Plough Corp, Elan Pharmaceuticals, Abbott Laboratories; Lectures: Centocor, Inc, Schering-Plough Corp, Abbott Laboratories, Elan Pharmaceuticals, Ferring USA; Grant Support: Giuliani, AstraZeneca Pharmaceuticals, Ferring USA, Danisco, Sanofi, Ferring France

Brian C. Feagan, MD—Grant/Research Support: Schering-Plough Corp, Otsuka Pharmaceuticals, Millenium Pharmaceuticals, Tillotts, Abbott Laboratories, Protein Design Labs, Boehringer-Ingelheim, Novartis, Centocor, Inc, Berlex; Consultant: Synta Pharmaceuticals, Millenium Pharmaceuticals, Schering Canada, Celltech Therapeutics Ltd, Centocor, Inc, Elan/Biogen, Serono, Janssen-Ortho, Protein Design Labs, Isis, Teva Pharmaceuticals, Santarus, Inc, Schering-Plough Corp; Speakers’ Bureau: AstraZeneca Pharmaceuticals; Member, Scientific Advisory Board: Protein Design Labs, AstraZeneca Pharmaceuticals, Elan/Biogen, Celltech, Synta Pharmaceuticals, Schering Canada; Stock Shareholder: Santarus, Inc

Richard N. Fedorak, MD—Consultant, Speakers’ Bureau, or Grant Funding: Abbott, Schering, Elan, USB, BMS, Centocor

Stephen B. Hanauer, MD—Consultant: Centocor, Abbott Laboratories, UCB Pharma, Elan Pharmaceuticals, PDL Biopharma, Millenium Pharmaceuticals, Berlex Laboratories, Bristol-Meyers-Squibb; Research Support: Centocor, Abbott Laboratories, UCB Pharma, Elan Pharmaceuticals, PDL Biopharma, BMS; Lecture Honorarium: Centocor, Abbott Laboratories, UCB Pharma, Elan Pharmaceuticals, PDL Biopharma

Michael A. Kamm, MD, PhD—Consultant: Abbott, Elan, Schering-Plough, UCB

Lloyd Mayer, MD—Consultant: Centocor, Inc, Abbott Laboratories, Protein Design Labs, Prometheus Labs, Salix

Carol Regueiro, MD—No financial relationships to disclose.

Paul Rutgeerts, MD—Speakers’ Bureau: Biogen Idec, Centocor, Inc, Elan Pharmaceuticals, Schering-Plough Corp; Advisor: Centocor, Inc, Schering-Plough Corp; Consultant: Millenium Pharmaceuticals, Protein Design Labs, Centocor, Schering-Plough, UCB Pharma, Abbott Laboratories, Bristol-Myers Squibb; Research support: Centocor, Schering-Plough, Abbott, UCB; Lecture honorarium: Centocor, Inc, Schering-Plough Corporation, UCB Pharma, Abbott Laboratories, Protein Design Labs.

William J. Sandborn, MD—Research Support: Centocor, Abbott Laboratories, UCB Pharma, Elan Pharmaceuticals, PDL Biopharma; Consultant: Centocor, Abbott Laboratories, UCB Pharma, Elan Pharmaceuticals, PDL Biopharma, Millenium Pharmaceuticals, Cerimon Pharmaceuticals, Isis Pharmaceuticals, Berlex Laboratories; Continuing Medical Education Unrestricted Grants: Centocor Abbott Laboratories, UCB Pharma, Elan Pharmaceuticals, PDL Biopharma

Bruce E. Sands, MD—Consultant: Centocor, Biogen/IDEC, Elan, Abbott Laboratories, Prometheus Laboratories, Shire Pharmaceuticals, Berlex, Protein Design Laboratories Biopharma, Otsuka America Pharmaceuticals Inc, Solvay Pharmaceuticals, Procter & Gamble Pharmaceuticals, Synta Pharmaceuticals, Avidia, Cerimon Pharmaceuticals, Bristol-Myers Squibb, Osiris, Millenium Pharmaceuticals; Research Support: Centocor, Elan, Abbott Laboratories, Prometheus Laboratories, Berlex, Otsuka, Synta Pharmaceuticals, Millenium Pharmaceuticals; Lectures: Centocor, Abbott Laboratories, Shire Pharmaceuticals, Berlex, Otsuka America Pharmaceuticals Inc, Procter & Gamble Pharmaceuticals

Stefan Schreiber, MD—Grant/Research Support: Centocor, Inc, Schering-Plough Corp, UCB Pharmaceuticals; Consultant: UCB Pharmaceuticals, Schering-Plough Corp, Elan Pharmaceuticals, Abbott Laboratories, Teva Pharmaceuticals, Boehringer-Ingelheim; Major Stock Shareholder: Conan’s AG

Stephan Targan, MD—Consultant: Scientific Advisory Board, Santarus, Inc, Protein Design Labs; Major Stock Shareholder: Prometheus Labs, Santarus, Inc; Other: Member, Board of Directors, Prometheus Labs

Simon Travis, MD—Adviser, Lecturer, Unrestricted Educational Grants, or Research Support: Abbott, Centocor, Schering Plough, UCB

Severine Vermeire, MD, PhD—Grants/Research Support: UCB; Consultancy: Astra-Zeneca, Ferring; Speakers’ Bureau: Schering-Plough, Abbott, Ferring, UCB; Advisory Committee: Shire, Ferring

PII: S0016-5085(07)00988-2

doi: 10.1053/j.gastro.2007.05.006

Gastroenterology
Volume 133, Issue 1 , Pages 312-339 , July 2007