Anti-TNF levels and anti-drug antibodies, immunosuppressants and clinical outcomes in inflammatory bowel disease

Expert Review of Gastroenterology and Hepatology

Volumn 9, Issue 4, 2015, Pages 497-505

  Ha, Christina ^a   Mathur, Jagrati ^b   Kornbluth, Asher ^c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Anti drug antibodies; Anti tumor necrosis factor agents; Crohn's disease; Immunogenicity; Immunosuppressants; Therapeutic drug levels; Ulcerative colitis

Indexed keywords

6 MERCAPTOPURINE DERIVATIVE; 6 METHYLTHIOINOSINE; ADALIMUMAB; ALLOPURINOL; AZATHIOPRINE; CERTOLIZUMAB PEGOL; DRUG ANTIBODY; GOLIMUMAB; IMMUNOSUPPRESSIVE AGENT; INFLIXIMAB; MERCAPTOPURINE; THIOGUANOSINE; TIOGUANINE; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; ANTIBODY; TUMOR NECROSIS FACTOR ALPHA;

ALLERGIC REACTION; ANTIBODY BLOOD LEVEL; BONE MARROW SUPPRESSION; CROHN DISEASE; DRUG BLOOD LEVEL; DRUG CONTRAINDICATION; DRUG MONITORING; DRUG SAFETY; DRUG WITHDRAWAL; HEADACHE; HEPATITIS B; HUMAN; HYPERSENSITIVITY; IMMUNOGENICITY; IMMUNOSUPPRESSIVE TREATMENT; INFLAMMATORY BOWEL DISEASE; LEUKOPENIA; LIVER TOXICITY; LUPUS LIKE SYNDROME; LYMPHOMA; LYMPHOPROLIFERATIVE DISEASE; MULTICENTER STUDY (TOPIC); NAUSEA; NEUROLOGIC DISEASE; OPPORTUNISTIC INFECTION; PANCREATITIS; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REMISSION; REVIEW; SKIN CANCER; ULCERATIVE COLITIS; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; COLITIS, ULCERATIVE; IMMUNOLOGY; PREDICTIVE VALUE; PROCEDURES; TIME; TREATMENT OUTCOME;

ANIMALS; ANTIBODIES; COLITIS, ULCERATIVE; CROHN DISEASE; DRUG MONITORING; HUMANS; IMMUNOSUPPRESSIVE AGENTS; PREDICTIVE VALUE OF TESTS; REMISSION INDUCTION; TIME FACTORS; TREATMENT OUTCOME; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84924404416     PISSN: 17474124     EISSN: 17474132     Source Type: Journal    
DOI: 10.1586/17474124.2015.983079     Document Type: Review

References (92)

1. Timmer A, McDonald JW, Macdonald JK. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2007;CD000478
2. Prefontaine E, Sutherland LR, Macdonald JK, et al. Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2009;CD000067
3. Prefontaine E, Macdonald JK, Sutherland LR. Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2009;CD000545
4. George J, Present DH, Pou R, et al. The long-term outcome of ulcerative colitis treated with 6-mercaptopurine. Am J Gastroenterol 1996;91:1711-14
5. D'Haens G, Baert F, van Assche G, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomized trial. Lancet 2008;371:660-7
6. Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for crohn's disease. N Engl J Med 2010;362:1383-95
7. Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology 2014;146:392-400.e3
8. 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;56:1226-31
9. Ordas I, Feagan BG, Sandborn WJ. Therapeutic drug monitoring of tumor necrosis factor antagonists in inflammatory bowel disease. Clin Gastroenterol Hepatol 2012;10:1079-87.quiz e85-6
10. Siegel CA, Marden SM, Persing SM, et al. 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;7:874-81
11. Toruner M, Loftus EV, Harmsen WS, et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008;134:929-36
12. Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infection and mortality in patients with crohn's disease: more than 5 years of follow-up in the TREAT registry. Am J Gastroenterol 2012;107:1409-22
13. Sahasranaman S, Howard D, Roy S. Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol 2008;64:753-67
14. Lichtenstein GR, Hanauer SB, Sandborn WJ. Management of Crohn's disease in adults. Am J Gastroenterol 2009;104:465-83
15. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010;105:501-23
16. Terdiman JP, Gruss CB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute guideline on the use of thiopurines, methotrexate, and anti-TNF-alpha biologic drugs for the induction and maintenance of remission in inflammatory Crohn's disease. Gastroenterology 2013;145:1459-63
17. Panes J, Lopez-Sanroman A, Bermejo F, et al. Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn's disease. Gastroenterology 2013;145:766-74.e1
18. Cosnes J, Bourrier A, Laharie D, et al. Early administration of azathioprine vs conventional management of Crohn's Disease: a randomized controlled trial. Gastroenterology 2013;145:758-65.e2 quiz e14-5
19. Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980;32:651-62
20. Gardiner SJ, Gearry RB, Begg EJ, et al. Thiopurine dose in intermediate and normal metabolizers of thiopurine methyltransferase may differ three-fold. Clin gastroenterol Hepatol 2008;6:654-60.quiz 604
21. Ansari A, Arenas M, Greenfield SM, et al. Prospective evaluation of the pharmacogenetics of azathioprine in the treatment of inflammatory bowel disease. Aliment Pharmacol Ther 2008;28:973-83
22. Osterman MT, Kundu R, Lichtenstein GR, et al. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology 2006;130:1047-53
23. Sparrow MP, Irving PM, Hanauer SB. Optimizing conventional therapies for inflammatory bowel disease. Curr Gastroenterol Rep 2009;11:496-503
24. Sparrow MP, Hande SA, Friedman S, et al. Effect of allopurinol on clinical outcomes in inflammatory bowel disease nonresponders to azathioprine or 6-mercaptopurine. Clin Gastroenterol Hepatol 2007;5:209-14
25. Leung Y, Sparrow MP, Schwartz M, et al. Long term efficacy and safety of allopurinol and azathioprine or 6-mercaptopurine in patients with inflammatory bowel disease. J Crohn Colitis 2009;3:162-7
26. Ansari A, Patel N, Sanderson J, et al. Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2010;31:640-7
27. Chevaux JB, Peyrin-Biroulet L, Sparrow MP. Optimizing thiopurine therapy in inflammatory bowel disease. Inflamm Bowel Dis 2011;17:1428-35
28. Siegel CA, Sands BE. Review article: practical management of inflammatory bowel disease patients taking immunomodulators. Aliment Pharmacol Ther 2005;22:1-16
29. Chaparro M, Ordas I, Cabre E, et al. Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients. Inflamm Bowel Dis 2013;19:1404-10
30. Kandiel A, Fraser AG, Korelitz BI, et al. Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut 2005;54:1121-5
31. Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 2009;374:1617-25
32. Rutgeerts P, Van Assche G, Vermeire S. Optimizing anti-TNF treatment in inflammatory bowel disease. Gastroenterology 2004;126:1593-610
33. Lichtenstein GR, Yan S, Bala M, et al. Remission in patients with Crohn's disease is associated with improvement in employment and quality of life and a decrease in hospitalizations and surgeries. Am J Gastroenterol 2004;99:91-6
34. Alzafiri R, Holcroft CA, Malolepszy P, et al. Infliximab therapy for moderately severe Crohn's disease and ulcerative colitis: a retrospective comparison over 6 years. Clin Exp Gastroenterol 2011;4:9-17
35. Munkholm P, Langholz E, Davidsen M, et al. Frequency of glucocorticoid resistance and dependency in Crohn's disease. Gut 1994;35:360-2
36. Kirman I, Whelan RL, Nielsen OH. Infliximab: mechanism of action beyond TNF-alpha neutralization in inflammatory bowel disease. Eur J Gastroenterol Hepatol 2004;16:639-41
37. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002;359:1541-9
38. Rutgeerts P, Diamond RH, Bala M, et al. Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease. Gastrointest Endosc 2006;63:433-42
39. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 1999;340:1398-405
40. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462-76
41. Colombel JF, 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;132:52-65
42. Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 2012;142:257-65.e1-3
43. Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut 2011;60:780-7
44. Lichtenstein GR. Comprehensive review: antitumor necrosis factor agents in inflammatory bowel disease and factors implicated in treatment response. Therap Adv Gastroenterol 2013;6:269-93
45. Lichtenstein GR, Thomsen OO, 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(7):600-9
46. Schreiber S, Colombel JF, Bloomfield R, et al. Increased response and remission rates in short-duration Crohn's disease with subcutaneous certolizumab pegol: an Analysis of PRECiSE 2 randomized maintenance trial data. Am J Gastroenterol 2010
47. Schreiber S, Rutgeerts P, Fedorak RN, et al. A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease. Gastroenterology 2005;129:807-18
48. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology 2014;146:96-109.e1
49. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 2014;146:85-95.quiz e14-5
50. Siegel CA, Hur C, Korzenik JR, et al. Risks and benefits of infliximab for the treatment of Crohn's disease. Clin Gastroenterol Hepatol 2006;4:1017-24.quiz 976
51. Long MD, Martin CF, Pipkin CA, et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology 2012;143:390-9.e1
52. Fellermann K. Adverse events of tumor necrosis factor inhibitors. Dig Dis 2013;31:374-8
53. Gisbert JP, Panes J. Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review. Am J Gastroenterol 2009;104:760-7
54. 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;348:601-8
55. Cornillie F, Hanauer S, Diamond R, et al. Early serum infliximab trough level, clinical disease activity and CRP as markers of sustained benefit of infliximab treatment in Crohn's disease: a post-hoc analysis of the ACCENT1 trial. Am J Gastroenterol 2011;106:S462-3
56. Reinisch W, Feagan B, Rutgeerts P, et al. Infliximab concentration and clinical outcome in patients with ulcerative colitis. Gastroenerology 2012;142:S114
57. 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;4:1248-54
58. 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;134:1861-8
59. 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;59:49-54
60. Vande Casteele N, Compernolle G, Ballet V, et al. Results on the optimisation phase of the prospective controlled trough level adapted infliximab treatment (TAXIT) trial. Gastroenerology 2012;142:S211-12
61. van Moerkercke W, Ackaert C, Compernolle G, et al. High infliximab trough levels are associated with mucosal healing in Crohn's disease. Gastroenerology 2010;138:S-60
62. 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;105:1133-9
63. 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;137:1628-40
64. Roblin X, Marotte H, Rinaudo M, et al. Association between pharmacokinetics of adalimumab and mucosal healing in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2014;12:80-4.e2
65. Roblin X, Rinaudo M, Del Tedesco E, et al. Development of an algorithm incorporating pharmacokinetics of adalimumab in inflammatory bowel diseases. Am J Gastroenterol 2014;109(8):1250-6
66. Colombel JF, Sandborn WJ, Allez M, et al. Association between plasma concentrations of certolizumab pegol and endoscopic outcomes of patients with Crohn's disease. Clin Gastroenterol Hepatol 2014;12:423-31.e1
67. 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 Crohns Colitis 2010;4:355-66
68. Bartelds GM, Krieckaert CL, Nurmohamed MT, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA 2011;305:1460-8
69. 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;2:542-53
70. Harding FA, Stickler MM, Razo J, et al. The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs 2010;2:256-65
71. Fasanmade AA, Adedokun OJ, Ford J, et al. Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis. Eur J Clin Pharmacol 2009;65:1211-28
72. Fasanmade AA, Adedokun OJ, Blank M, et al. 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;33:946-64
73. 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;124:917-24
74. Baert F, Lockton S, Hauenstein S, et al. Antibodies to adalimumab predict inflammation in Crohn's patients on maintenance adalimumab therapy. Gastroenterology 2014;146:S242
75. West RL, Zelinkova Z, Wolbink GJ, et al. Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn's disease. Aliment Pharmacol Ther 2008;28:1122-6
76. 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;8:688-95.e2
77. Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med 2007;357:228-38
78. Sandborn WJ, Hanauer SB, Rutgeerts P, et al. Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial. Gut 2007;56:1232-9
79. Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med 2007;357:239-50
80. Feagan BG, McDonald JW, Panaccione R, et al. Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn's disease. Gastroenterology 2014;146:681-8.e1
81. Baert F, Drobne D, Gils A, et al. Early trough levels and antibodies to infliximab predict safety and success of reinitiation of infliximab therapy. Clin Gastroenterol Hepatol 2014;12(9):1474-81.e2
82. Vande Casteele N, Gils A, Singh S, et al. Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am J Gastroenterol 2013;108:962-71
83. 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;103:944-8
84. Wang SL, Ohrmund L, Hauenstein S, et al. Development and validation of a homogeneous mobility shift assay for the measurement of infliximab and antibodies-to-infliximab levels in patient serum. J Immunol Methods 2012;382:177-88
85. Steenholdt C, Al-khalaf M, Brynskov J, et al. Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease. Inflamm Bowel Dis 2012;18:2209-17
86. Velayos F, Sheibani S, Lockton S, et al. Prevalence of antibodies to adalimumab (ATA) and correlation between ATA and low serum drug concentration and clinical symptoms in a prospective sample of IBD patients. Gastroenerology 2013;144:S91
87. Feagan B, Greenberg GR, Singh S, et al. Novel infliximab and antibody to infliximab (ATI) assays are predictive of disease activity in patients with Crohn's disease. Gastroenterology 2012;142:S114
88. Steenholdt C, Bendtzen K, Brynskov J, et al. Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn's disease. Scand J Gastroenterol 2011;46:310-18
89. Oussalah A, Chevaux JB, Fay R, et al. Predictors of infliximab failure after azathioprine withdrawal in Crohn's disease treated with combination therapy. Am J Gastroenterol 2010;105:1142-9
90. Steenholdt C, Brynskov J, Thomsen OO, 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
91. Velayos FS, Kahn JG, Sandborn WJ, et al. A test-based strategy is more cost effective than empiric dose escalation for patients with Crohn's disease who lose responsiveness to infliximab. Clin Gastroenterol Hepatol 2013;11:654-66
92. Rubin DT, Uluscu O, Sederman R. Response to biologic therapy in Crohn's disease is improved with early treatment: an analysis of health claims data. Inflamm Bowel Dis 2012;18:2225-31