Pharmaceutical Research

, Volume 34, Issue 8, pp 1556–1563 | Cite as

Therapeutic Drug Monitoring of Golimumab in the Treatment of Ulcerative Colitis

  • Niels Vande CasteeleEmail author
  • Reena Khanna
Expert Review


Ulcerative colitis (UC) is a relapsing-remitting chronic inflammatory disorder affecting the mucosal surface in a continuous manner from the rectum through part of, or the entire, colon. Patients with severe disease and those who become refractory or intolerant to corticosteroids and/or immunosuppressants, require treatment with biologic agents that target tumor necrosis factor-α (TNF). Golimumab, a fully human monoclonal antibody, is the latest TNF antagonist to get approved for the treatment of moderate-to-severe UC. Subcutaneously administered golimumab induces and maintains clinical response, remission, and mucosal healing. Serum concentrations of golimumab are associated with response to therapy, as patients with higher drug exposure are more likely to achieve these outcomes. Since various patient and disease-related factors were shown to influence the pharmacokinetics of TNF antagonists, drug exposure may be variable over time and between patients, affecting success of therapy. A major contributing factor is immunogenicity, with development of anti-drug antibodies (ADAb) and an accelerated clearance of drug as a result. Although there is a growing body of evidence to support therapeutic drug monitoring (TDM) for infliximab and adalimumab, two other TNF antagonists, only limited data is available for golimumab. In addition, the clinically important drug exposure thresholds are not widely known, which has limited the use of TDM for golimumab in clinical practice. This review summarizes available data regarding the use of golimumab for UC, with emphasis on the pharmacokinetics, exposure-response relationship, and the role of TDM in optimizing therapy.

Key Words

anti drug antibodies anti-TNF immunogenicity inflammatory bowel disease pharmacokinetics 





C-reactive protein


Enzyme-linked immune-sorbent assay


Homogenous mobility shift assay


High pressure liquid chromatography


Inflammatory bowel disease






Reticuloendothelial system




Receiver operating characteristic




Therapeutic drug monitoring


Target mediated drug disposition


Tumor necrosis factor-α


Ulcerative colitis


Variable number tandem repeat


  1. 1.
    Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46–54. e42; quiz e30CrossRefPubMedGoogle Scholar
  2. 2.
    Ordas I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet. 2012;380(9853):1606–19.CrossRefPubMedGoogle Scholar
  3. 3.
    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(23):2462–76.CrossRefPubMedGoogle Scholar
  4. 4.
    Sandborn WJ, van Assche G, Reinisch W, Colombel JF, D'Haens G, Wolf DC, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142(2):257–65. e1–3CrossRefPubMedGoogle Scholar
  5. 5.
    Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, et al. Subcutaneous Golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(1):85–95.CrossRefPubMedGoogle Scholar
  6. 6.
    Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(1):96–109. e1CrossRefPubMedGoogle Scholar
  7. 7.
    Allez M, Vermeire S, Mozziconacci N, Michetti P, Laharie D, Louis E, et al. The efficacy and safety of a third anti-TNF monoclonal antibody in Crohn's disease after failure of two other anti-TNF antibodies. Aliment Pharmacol Ther. 2010;31(1):92–101.CrossRefPubMedGoogle Scholar
  8. 8.
    Gisbert JP, Panes J. Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review. Am J Gastroenterol. 2009;104(3):760–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Adedokun OJ, Sandborn WJ, Feagan BG, Rutgeerts P, Xu Z, Marano CW, et al. Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. Gastroenterology. 2014;147(6):1296–307. e5CrossRefPubMedGoogle Scholar
  10. 10.
    Paul S, Del Tedesco E, Marotte H, Rinaudo-Gaujous M, Moreau A, Phelip JM, et al. Therapeutic drug monitoring of infliximab and mucosal healing in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis. 2013;19(12):2568–76.CrossRefPubMedGoogle Scholar
  11. 11.
    Yanai H, Lichtenstein L, Assa A, Mazor Y, Weiss B, Levine A, et al. Levels of drug and antidrug antibodies are associated with outcome of interventions after loss of response to infliximab or adalimumab. Clin Gastroenterol Hepatol. 2015;13(3):522–30. e2CrossRefPubMedGoogle Scholar
  12. 12.
    Roblin X, Marotte H, Rinaudo M, Del Tedesco E, Moreau A, Phelip JM, et al. Association between pharmacokinetics of adalimumab and mucosal healing in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2014;12(1):80–4. e2CrossRefPubMedGoogle Scholar
  13. 13.
    Ternant D, Aubourg A, Magdelaine-Beuzelin C, Degenne D, Watier H, Picon L, et al. Infliximab pharmacokinetics in inflammatory bowel disease patients. Ther Drug Monit. 2008;30(4):523–9.PubMedGoogle Scholar
  14. 14.
    Ungar B, Chowers Y, Yavzori M, Picard O, Fudim E, Har-Noy O, et al. The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab. Gut. 2014;63(8):1258–64.CrossRefPubMedGoogle Scholar
  15. 15.
    Vande Casteele N, Gils A, Singh S, Ohrmund L, Hauenstein S, Rutgeerts P, et al. Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am J Gastroenterol. 2013;108(6):962–71.CrossRefPubMedGoogle Scholar
  16. 16.
    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(4):635–46.CrossRefPubMedGoogle Scholar
  17. 17.
    Bortlik M, Duricova D, Malickova K, Machkova N, Bouzkova E, Hrdlicka L, et al. Infliximab trough levels may predict sustained response to infliximab in patients with Crohn's disease. J Crohns Colitis. 2013;7(9):736–43.CrossRefPubMedGoogle Scholar
  18. 18.
    Hibi T, Sakuraba A, Watanabe M, Motoya S, Ito H, Sato N, et al. C-reactive protein is an indicator of serum infliximab level in predicting loss of response in patients with Crohn's disease. J Gastroenterol. 2014;49(2):254–62.CrossRefPubMedGoogle Scholar
  19. 19.
    Levesque BG, Greenberg GR, Zou G, Sandborn WJ, Singh S, Hauenstein S, et al. A prospective cohort study to determine the relationship between serum infliximab concentration and efficacy in patients with luminal Crohn's disease. Aliment Pharmacol Ther. 2014;39(10):1126–35.CrossRefPubMedGoogle Scholar
  20. 20.
    Vande Casteele N, Khanna R, Levesque BG, Stitt L, Zou GY, Singh S, et al. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease. Gut. 2015;64(10):1539–45.CrossRefPubMedGoogle Scholar
  21. 21.
    Yarur AJ, Jain A, Hauenstein SI, Quintero MA, Barkin JS, Deshpande AR, et al. Higher adalimumab levels are associated with histologic and endoscopic remission in patients with Crohn's disease and ulcerative colitis. Inflamm Bowel Dis. 2016;22(2):409–15.CrossRefPubMedGoogle Scholar
  22. 22.
    Mazor Y, Almog R, Kopylov U, Ben Hur D, Blatt A, Dahan A, et al. Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn's disease. Aliment Pharmacol Ther. 2014;40(6):620–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Arias MT, Vande Casteele N, Vermeire S, de Buck van Overstraeten A, Billiet T, Baert F, et al. A panel to predict long-term outcome of infliximab therapy for patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2015;13(3):531–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Cornillie F, Hanauer SB, Diamond RH, Wang J, Tang KL, Xu Z, et al. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial. Gut. 2014;63(11):1721–7.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Baert F, Noman M, Vermeire S, Van Assche G. G DH, Carbonez A, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med. 2003;348(7):601–8.Google Scholar
  26. 26.
    Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial. Gastroenterology. 2003;124(4):917–24.CrossRefPubMedGoogle Scholar
  27. 27.
    Nanda KS, Cheifetz AS, Moss AC. Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (IBD): a meta-analysis. Am J Gastroenterol. 2013;108(1):40–7. quiz 8CrossRefPubMedGoogle Scholar
  28. 28.
    Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010;362(15):1383–95.CrossRefPubMedGoogle Scholar
  29. 29.
    Adedokun OJ, Xu Z, Marano CW, Strauss R, Zhang H, Johanns J, et al. Pharmacokinetics and exposure-response relationship of Golimumab in patients with moderately-to-severely active ulcerative colitis: results from phase 2/3 PURSUIT induction and maintenance studies. J Crohns Colitis. 2017;11(1):35–46.CrossRefPubMedGoogle Scholar
  30. 30.
    Papamichael K, Gils A, Rutgeerts P, Levesque BG, Vermeire S, Sandborn WJ, et al. Role for therapeutic drug monitoring during induction therapy with TNF antagonists in IBD: evolution in the definition and management of primary nonresponse. Inflamm Bowel Dis. 2015;21(1):182–97.CrossRefPubMedGoogle Scholar
  31. 31.
    Khanna R, Sattin BD, Afif W, Benchimol EI, Bernard EJ, Bitton A, et al. Review article: a clinician's guide for therapeutic drug monitoring of infliximab in inflammatory bowel disease. Aliment Pharmacol Ther. 2013;38(5):447–59.CrossRefPubMedGoogle Scholar
  32. 32.
    Afif W, Loftus Jr EV, Faubion WA, Kane SV, Bruining DH, Hanson KA, et al. Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol. 2010;105(5):1133–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Fallingborg J, Christensen LA, et al. Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut. 2014;63(6):919–27.CrossRefPubMedGoogle Scholar
  34. 34.
    Vande Casteele N, Ferrante M, Van Assche G, Ballet V, Compernolle G, Van Steen K, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148(7):1320–9. e3CrossRefPubMedGoogle Scholar
  35. 35.
    Shealy DJ, Cai A, Staquet K, Baker A, Lacy ER, Johns L, et al. Characterization of golimumab, a human monoclonal antibody specific for human tumor necrosis factor alpha. MAbs. 2010;2(4):428–39.CrossRefPubMedGoogle Scholar
  36. 36.
    Kay J, Matteson EL, Dasgupta B, Nash P, Durez P, Hall S, et al. Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum. 2008;58(4):964–75.CrossRefPubMedGoogle Scholar
  37. 37.
    Keystone E, Genovese MC, Klareskog L, Hsia EC, Hall S, Miranda PC, et al. Golimumab in patients with active rheumatoid arthritis despite methotrexate therapy: 52-week results of the GO-FORWARD study. Ann Rheum Dis. 2010;69(6):1129–35.CrossRefPubMedGoogle Scholar
  38. 38.
    Emery P, Fleischmann RM, Moreland LW, Hsia EC, Strusberg I, Durez P, et al. Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis Rheum. 2009;60(8):2272–83.CrossRefPubMedGoogle Scholar
  39. 39.
    Smolen JS, Kay J, Doyle MK, Landewe R, Matteson EL, Wollenhaupt J, et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009;374(9685):210–21.CrossRefPubMedGoogle Scholar
  40. 40.
    Braun J, Deodhar A, Inman RD, van der Heijde D, Mack M, Xu S, et al. Golimumab administered subcutaneously every 4 weeks in ankylosing spondylitis: 104-week results of the GO-RAISE study. Ann Rheum Dis. 2012;71(5):661–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Kavanaugh A, van der Heijde D, McInnes IB, Mease P, Krueger GG, Gladman DD, et al. Golimumab in psoriatic arthritis: one-year clinical efficacy, radiographic, and safety results from a phase III, randomized, placebo-controlled trial. Arthritis Rheum. 2012;64(8):2504–17.CrossRefPubMedGoogle Scholar
  42. 42.
    Rutgeerts P, Feagan BG, Marano CW, Padgett L, Strauss R, Johanns J, et al. Randomised clinical trial: a placebo-controlled study of intravenous golimumab induction therapy for ulcerative colitis. Aliment Pharmacol Ther. 2015;42(5):504–14.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004;93(11):2645–68.CrossRefPubMedGoogle Scholar
  44. 44.
    Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008;84(5):548–58.CrossRefPubMedGoogle Scholar
  45. 45.
    Billiet T, Dreesen E, Cleynen I, Wollants WJ, Ferrante M, Van Assche G, et al. A genetic variation in the neonatal fc-receptor affects anti-TNF drug concentrations in inflammatory bowel disease. Am J Gastroenterol. 2016;111(10):1438–45.CrossRefPubMedGoogle Scholar
  46. 46.
    Xu Z, Wang Q, Zhuang Y, Frederick B, Yan H, Bouman-Thio E, et al. Subcutaneous bioavailability of golimumab at 3 different injection sites in healthy subjects. J Clin Pharmacol. 2010;50(3):276–84.CrossRefPubMedGoogle Scholar
  47. 47.
    Zhou H, Jang H, Fleischmann RM, Bouman-Thio E, Xu Z, Marini JC, et al. Pharmacokinetics and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis. J Clin Pharmacol. 2007;47(3):383–96.CrossRefPubMedGoogle Scholar
  48. 48.
    Zhuang Y, Xu Z, Frederick B, de Vries DE, Ford JA, Keen M, et al. Golimumab pharmacokinetics after repeated subcutaneous and intravenous administrations in patients with rheumatoid arthritis and the effect of concomitant methotrexate: an open-label, randomized study. Clin Ther. 2012;34(1):77–90.CrossRefPubMedGoogle Scholar
  49. 49.
    Xu Z, Vu T, Lee H, Hu C, Ling J, Yan H, et al. Population pharmacokinetics of golimumab, an anti-tumor necrosis factor-alpha human monoclonal antibody, in patients with psoriatic arthritis. J Clin Pharmacol. 2009;49(9):1056–70.CrossRefPubMedGoogle Scholar
  50. 50.
    Rutgeerts P, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn's disease. Gastroenterology. 2004;126(2):402–13.CrossRefPubMedGoogle Scholar
  51. 51.
    Maser EA, Villela R, Silverberg MS, Greenberg GR. Association of Trough Serum Infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease. Clin Gastroenterol Hepatol. 2006;4(10):1248–54.CrossRefPubMedGoogle Scholar
  52. 52.
    Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010;59(1):49–54.CrossRefPubMedGoogle Scholar
  53. 53.
    Schellekens H, Casadevall N. Immunogenicity of recombinant human proteins: causes and consequences. J Neurol. 2004;251 Suppl 2:Ii4–Ii9.Google Scholar
  54. 54.
    Hommes DW, van Deventer SJ. Infliximab therapy in Crohn's disease: safety issues. Neth J Med. 2003;61(4):100–4.PubMedGoogle Scholar
  55. 55.
    Gamarra RM, McGraw SD, Drelichman VS, Maas LC. Serum sickness-like reactions in patients receiving intravenous infliximab. J Emerg Med. 2006;30(1):41–4.CrossRefPubMedGoogle Scholar
  56. 56.
    Fasanmade AA, Adedokun OJ, Ford J, Hernandez D, Johanns J, Hu C, et al. Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis. Eur J Clin Pharmacol. 2009;65(12):1211–28.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Fasanmade AA, Adedokun OJ, Blank M, Zhou H, Davis HM. Pharmacokinetic properties of infliximab in children and adults with Crohn's disease: a retrospective analysis of data from 2 phase III clinical trials. Clin Ther. 2011;33(7):946–64.CrossRefPubMedGoogle Scholar
  58. 58.
    Wolbink GJ, Voskuyl AE, Lems WF, de Groot E, Nurmohamed MT, Tak PP, 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(5):704–7.CrossRefPubMedGoogle Scholar
  59. 59.
    Mould DR, Green B. Pharmacokinetics and pharmacodynamics of monoclonal antibodies: concepts and lessons for drug development. BioDrugs. 2010;24(1):23–39.CrossRefPubMedGoogle Scholar
  60. 60.
    Tabrizi MA, Tseng CM, Roskos LK. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006;11(1–2):81–8.CrossRefPubMedGoogle Scholar
  61. 61.
    Rosario M, Dirks NL, Gastonguay MR, Fasanmade AA, Wyant T, Parikh A, et al. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease. Aliment Pharmacol Ther. 2015;42(2):188–202.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Brandse JF, Mathot RA, van der Kleij D, Rispens T, Ashruf Y, Jansen JM, et al. Pharmacokinetic features and presence of antidrug antibodies associate with response to infliximab induction therapy in patients with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol. 2016;14(2):251–8. e1–2CrossRefPubMedGoogle Scholar
  63. 63.
    Zhu X, Meng G, Dickinson BL, Li X, Mizoguchi E, Miao L, et al. MHC class I-related neonatal fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. J Immunol. 2001;166(5):3266–76.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Brambell FW, Hemmings WA, Morris IG. A theoretical model of gamma-globulin catabolism. Nature. 1964;203:1352–4.CrossRefPubMedGoogle Scholar
  65. 65.
    Beeken WL, Busch HJ, Sylwester DL. Intestinal protein loss in Crohn's disease. Gastroenterology. 1972;62(2):207–15.PubMedGoogle Scholar
  66. 66.
    Brandse JF, van den Brink GR, Wildenberg ME, van der Kleij D, Rispens T, Jansen JM, et al. Loss of infliximab into feces is associated with lack of response to therapy in patients with severe ulcerative colitis. Gastroenterology. 2015;149(2):350–5. e2CrossRefPubMedGoogle Scholar
  67. 67.
    Peyrin-Biroulet L, Chamaillard M, Gonzalez F, Beclin E, Decourcelle C, Antunes L, et al. Mesenteric fat in Crohn's disease: a pathogenetic hallmark or an innocent bystander? Gut. 2007;56(4):577–83.CrossRefPubMedGoogle Scholar
  68. 68.
    Ungar B, Kopylov U, Engel T, Yavzori M, Fudim E, Picard O, et al. Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab. Aliment Pharmacol Ther. 2017;45:276–82.Google Scholar
  69. 69.
    Detrez I, Dreesen E, Van Stappen T, de Vries A, Brouwers E, Van Assche G, et al. Variability in Golimumab exposure: A 'Real-Life' observational study in active ulcerative colitis. J Crohns Colitis. 2016;10(5):575–81.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Martin S, del Agua AR, Torres N, Pascual-Salcedo D, Plasencia C, Ruiz-Arguello B, et al. Comparison study of two commercially available methods for the determination of golimumab and anti-golimumab antibody levels in patients with rheumatic diseases. Clin Chem Lab Med. 2015;53(11):e297–9.CrossRefPubMedGoogle Scholar
  71. 71.
    Jurado T, Plasencia C, Martin S, Navarro R, Bonilla G, Villalba A, et al. FRI0138 Comparison of Golimumab levels detected by two different enzyme-linked immunosorbent assays: Promonitor VS Sanquin. Ann Rheum Dis. 2015;74(Suppl 2):471.CrossRefGoogle Scholar
  72. 72.
    Van Stappen T, Brouwers E, Vermeire S, Gils A. Validation of a sample pretreatment protocol to convert a drug-sensitive into a drug-tolerant anti-infliximab antibody immunoassay. Drug Test Anal. 2017;9:243–7.CrossRefPubMedGoogle Scholar
  73. 73.
    Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, Bryant RV, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110(9):1324–38.CrossRefPubMedGoogle Scholar
  74. 74.
    Cooney RM, Warren BF, Altman DG, Abreu MT, Travis SP. Outcome measurement in clinical trials for ulcerative colitis: towards standardisation. Trials. 2007;8:17.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    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(2):763–86.CrossRefPubMedGoogle Scholar
  76. 76.
    Floren CH, Benoni C, Willen R. Histologic and colonoscopic assessment of disease extension in ulcerative colitis. Scand J Gastroenterol. 1987;22(4):459–62.CrossRefPubMedGoogle Scholar
  77. 77.
    Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126(2):451–9.CrossRefPubMedGoogle Scholar
  78. 78.
    Xu Z, Seitz K, Fasanmade A, Ford J, Williamson P, Xu W, et al. Population pharmacokinetics of infliximab in patients with ankylosing spondylitis. J Clin Pharmacol. 2008;48(6):681–95.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of MedicineUniversity of California San DiegoCaliforniaUSA
  2. 2.Robarts Clinical Trials Inc.Robarts Research InstituteLondonCanada
  3. 3.Department of MedicineUniversity of Western OntarioLondonCanada

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