• 1
    Peyrin-Biroulet L, Deltenre P, Suray ND, et al. Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol. 2008; 6: 644652.
  • 2
    REMICADE [prescribing information]. Malvern, PA: Centocor Ortho Biotech, Inc.; 2011.
  • 3
    HUMIRA [prescribing information]. North Chicago, IL: Abbott Laboratories; 2011.
  • 4
    CIMZIA [prescribing information]. Smyrna, GA: UCB; 2009.
  • 5
    Allez M, Karmiris K, Louis E, et al. Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: definitions, frequency and pharmacological aspects. J Crohn's Colitis. 2010; 4: 355366.
  • 6
    Bendtzen K, Ainsworth M, Steenholdt C, et al. Individual medicine in inflammatory bowel disease: monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies. Scand J Gastroenterol. 2009; 44: 774781.
  • 7
    Afif W, Loftus EV, Faubion WA, et al. Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol. 2010; 105: 11331139.
  • 8
    Garimella T, Peng J, Beck K, et al. Pharmacokinetics of adalimumab in a long-term investigation of the induction and maintenance of remission in patients with Crohn's disease (CLASSIC I and CLASSIC II). Gastroenterology. 2006; 130( 4 suppl 2): A481.
  • 9
    St. Clair EW, Wagner CL, Fasanmade AA, et al. The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis. Arthritis Rheum. 2002; 46: 14511459.
  • 10
    Keizer RJ, Huitema ADR, Schellens JHM, et al. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010; 48: 493507.
  • 11
    Mould D, Green B. Pharmacokinetics and pharmacodynamics of monoclonal antibodies: concepts and lessons for drug development. Biodrugs. 2010; 24: 2339.
  • 12
    Raghavan M, Bjorkman P. Fc receptors and their interactions with immunoglobulins. Annu Rev Cell Dev Biol. 1996; 12: 181220.
  • 13
    Tabrizi M, Tseng C-M, Roskos L. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006; 11: 8188.
  • 14
    Fiers W. Tumor necrosis factor: characterization at the molecular, cellular and in vivo level. FEBS Lett. 1991; 285: 195212.
  • 15
    Murch S, Lamkin V, Savage M, et al. Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease. Gut. 1991; 32: 913917.
  • 16
    Murch S, Braegger C, Walker-Smith J, et al. Location of tumour necrosis factor alpha by immunohistochemistry in chronic inflammatory bowel disease. Gut. 1993; 34: 17051709.
  • 17
    Vermeire S, Van Assche G, Rutgeerts P. C-reactive protein as a marker for inflammatory bowel disease. Inflamm Bowel Dis. 2004; 10: 661665.
  • 18
    Colombel JF, Solem CA, Sandborn WJ, et al. Quantitative measurement and visual assessment of ileal Crohn's disease activity by computed tomography enterography: correlation with endoscopic severity and C reactive protein. Gut. 2006; 55: 15611567.
  • 19
    Fasanmade AA, Adedokun OJ, Ford J, et al. Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis. Eur J Pharmacol. 2009; 65: 12111228.
  • 20
    Wolbink GJ, Voskuyl AE, Lems WF, et al. Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2005; 64: 704707.
  • 21
    Fasanmade AA, Adedokun OJ, Olson A, et al. Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis. Int J Clin Pharmacol Ther. 2010; 48: 297308.
  • 22
    Moran A, Jones A, Asquith P. Laboratory markers of colonoscopic activity in ulcerative colitis and Crohn's colitis. Scand J Gastroenterol. 1995; 30: 356360.
  • 23
    Champman AP. PEGylated antibodies and antibody fragments for improved therapy: a review. Adv Drug Del Rev. 2002; 54: 531545.
  • 24
    Nestorov I. Clinical pharmacokinetics of tumor necrosis factor antagonists. J Rheumatol. 2005; 32( suppl): 1318.
  • 25
    Ternant D, Aubourg A, Magdelaine-Beuzelin C, et al. Infliximab pharmacokinetics in inflammatory bowel disease patients. Ther Drug Monit. 2008; 30: 523529.
  • 26
    Weisman MH, Moreland LW, Furst DE, et al. Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study. Clin Ther. 2003; 25: 17001721.
  • 27
    Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor á monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. 1998; 41: 15521563.
  • 28
    Farrell RJ, Alsahli M, Jeen YT, et al. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial. Gastroenterology. 2003; 124: 917924.
  • 29
    Karmiris K, Paintaud G, Noman M, et al. Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn's disease. Gastroenterology. 2009; 137: 16281640.
  • 30
    Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010; 362: 13831395.
  • 31
    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: 18611868.
  • 32
    Van Assche G. Immunogenicity of anti-TNF antibodies. Has the veil been lifted? Gut. 2011; 60: 285286.
  • 33
    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: 601608.
  • 34
    Lichtenstein G, Thomsen O, Schreiber S, et al. Continuous therapy with certolizumab pegol maintains remission of patients with Crohn's disease for up to 18 months. Clin Gastroenterol Hepatol. 2010; 8: 600609.
  • 35
    Sandborn WJ, Schreiber S, Hanauer SB, et al. Reinduction with certolizumab pegol in patients with relapsed Crohn's disease: results from the PRECiSE 4 study. Clin Gastroenterol Hepatol. 2010; 8: 696702.
  • 36
    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: 944948.
    Direct Link:
  • 37
    Cassinotti A, Travis S. Incidence and significance of immunogenicity to infliximab in Crohn's disease: a critical systematic review. Inflamm Bowel Dis. 2009; 15: 12641275.
  • 38
    Wang S, Ohrmund L, Ling N, et al. Analysis of anti-drug antibodies (ADA) to adalimumab in patient serum using a novel homogeneous mobility shift assay. Am J Gastroenterol. 2010; 105( suppl 1): S444S445.
  • 39
    Wang S, Ohrmund L, Singh S. Measurement of human anti-chimeric antibodies (HACA) and infliximab levels in patient serum using a novel homoegeous assay. Gastroenterology. 2010; 138( 5 suppl 1): S684S685.
  • 40
    Van Schouwenburg P, Bartelds G, Hart M, et al. A novel method for the detection of antibodies to adalimumab in the presence of drug reveals “hidden” immunogenicity in rheumatoid arthritis. J Immunol Methods. 2010; 362: 8288.
  • 41
    Sandborn W, Feagan B, Hanauer S, 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: 512530.
  • 42
    Bruining DA, Sandborn WJ. Do not assume symptoms indicate failure of anti-tumor necrosis factor therapy in Crohn's disease. Clin Gastroenterol Hepatol. 2011; 9: 395399.
  • 43
    Fasanmade A, Olson A, Bag W, et al. Relationship between infliximab pharmacokinetics and improvement in Crohn's disease. Gastroenterology. 2002; 122( suppl 4): A617A618.
  • 44
    Fasanmade AA, Marsters P, Munsanje E, et al. Infliximab pharmacokinetics and improvement in fistulizing Crohn's disease. Gastroenterology. 2003; 124( 4 suppl 1): A61.
  • 45
    Feagan BG, McDonald JW, Panaccione R, et al. Methotrexate for the prevention of antibodies to infliximab in patients with Crohn's disease. Gastroenterology. 2010; 138( 5 suppl 1): S167S168.
  • 46
    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: 12481254.
  • 47
    Van Moerkercke W, Ackaert C, Compernolle G, et al. High infliximab trough levels are associated with mucosal healing in Crohn's disease. Gastroenterology. 2010; 5( suppl 1): S60.
  • 48
    Seow CH, Newman A, Irwin SP, et al. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010; 59: 4954.
  • 49
    Li J, Chiu Y, Robinson A, et al. Evaluation of potential correlations between serum adalimumab concentration and remission in patients with Crohn's disease in CLASSIC I and II. J Crohn's Colitis. 2010; 4( suppl): S73.
  • 50
    Schreiber S, Khaliq-Kareemi M, Lawrance I, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007; 357: 239250.
  • 51
    Sandborn WJ, Abreu MT, D'Haens G, et al. Certolizumab pegol in patients with moderate to severe Crohn's disease and secondary failure to infliximab. Clin Gastroenterol Hepatol. 2010; 8: 688695.
  • 52
    Hanauer SB, Wagner CL, Bala M, et al. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn's disease. Clin Gastroenterol Hepatol. 2004; 2: 542553.
  • 53
    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: 12261231.
  • 54
    Ben-Horin S, Yavzori M, Katz L, et al. The immunogenic part of infliximab is the F(ab')2, but measuring antibodies to the intact infliximab molecule is more clinically useful. Gut. 2011; 60: 4148.
  • 55
    West RL, Zelinkova Z, Wolbink GJ, et al. Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn's disease. Aliment Pharmacol Ther. 2008; 28: 11221126.
  • 56
    Sandborn W, Hanauer S, Rutgeerts P, et al. Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial. Gut. 2007; 56: 12321239.
  • 57
    Bartelds GM, Krieckaert CLM, Nurmohamed MT, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment tailure during long-term follow-up. JAMA. 2011; 305: 14601468.
  • 58
    Sandborn W, Feagan B, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007; 257: 228238.
  • 59
    Spector R, Park G, Johnson G, et al. Therapeutic drug monitoring. Clin Pharmacol Ther. 1988; 43: 345353.
  • 60
    Reynolds D, Aronson J. Making the most of plasma drug concentration measurements. BMJ. 1993; 306: 4851.
  • 61
    Serum infliximab/HACA data sheet. San Diego, CA: Prometheus Laboratories; 2006.
  • 62
    Vermeire S, Gabriels F, Ballet V, et al. The effect of dose escalation on trough levels in patients who lost response to infliximab. Gut. 2010; 59( suppl III): A81.
  • 63
    Pariente B, Pineton de Chambrun G, Krysiek R, et al. Clinical significance of infliximab and human antichimeric antibodies concentrations in patients with inflammatory bowel disease who lost response to infliximab therapy. Inflamm Bowel Dis. 2011, DOI: 10.1002/ibd.21839.
  • 64
    Bartelds GM, Wijbrandts CA, Nurmohamed MT, et al. Clinical response to adalimumab: relationship to antiadalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis. 2007; 66: 921926.
  • 65
    Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002; 359: 15411549.
  • 66
    Colombel J-F, 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: 5265.
  • 67
    Westhovens R, Yocum D, Han J, et al. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities. Arthritis Rheum. 2006; 54: 10751086.
  • 68
    Cleynen I, Van Moerkercke, W, Juergens M, et al. Anti-TNF induced cutaneous lesions in IBD patients: characterization and search for predisposing factors. Gut. 2010; 59( suppl III): A1.
  • 69
    Finckh A, Dudler J, Wermelinger F, et al. Influence of anti-infliximab antibodies and residual infliximab concentrations on the occurrence of acquired drug resistance to infliximab in rheumatoid arthritis patients. Joint Bone Spine. 2010; 4: 313318.
  • 70
    Rea R, Blair C. Optimizing use of aminoglycosides in the critically ill. Semin Respir Crit Care Med. 2007; 28: 596603.