Stopping anti-TNF agents in patients with crohn's disease in remission: Is it a feasible long-term strategy?

Inflammatory Bowel Diseases

Volumn 20, Issue 4, 2014, Pages 757-766

  Sorrentino, Dario ^a,b,c   Nash, Peter ^d   Viladomiu, Monica ^b   Hontecillas, Raquel ^b   Bassaganya Riera, Josep ^b  

^a VIRGINIA TECH CARILION SCHOOL OF MEDICINE   (United States)

^b VIRGINIA BIOINFORMATICS INSTITUTE   (United States)

^c UNIVERSITY OF UDINE   (Italy)

^d UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

Anti TNF agents; Crohn's disease; Immunomodulators; Long term therapy; Stopping biologics

Indexed keywords

ADALIMUMAB; AZATHIOPRINE; BIOLOGICAL PRODUCT; CERTOLIZUMAB PEGOL; CORTICOSTEROID; INFLIXIMAB; MERCAPTOPURINE; METHOTREXATE; STEROID; TUMOR NECROSIS FACTOR ANTIBODY; TUMOR NECROSIS FACTOR INHIBITOR; MONOCLONAL ANTIBODY; NONSTEROID ANTIINFLAMMATORY AGENT; TUMOR NECROSIS FACTOR ALPHA;

COLONOSCOPY; CROHN DISEASE; CROHN DISEASE ACTIVITY INDEX; DISEASE CONTROL; DRUG EFFICACY; DRUG WITHDRAWAL; HUMAN; LONG TERM CARE; PRIORITY JOURNAL; RECURRENCE RISK; RELAPSE; REMISSION; REVIEW; TREATMENT WITHDRAWAL; ANTAGONISTS AND INHIBITORS; IMMUNOLOGY; PROCEDURES; RECURRENT DISEASE; RISK FACTOR;

ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTIBODIES, MONOCLONAL; CROHN DISEASE; HUMANS; LONG-TERM CARE; RECURRENCE; REMISSION INDUCTION; RISK FACTORS; TUMOR NECROSIS FACTOR-ALPHA; WITHHOLDING TREATMENT;

EID: 84898721366     PISSN: 10780998     EISSN: 15364844     Source Type: Journal    
DOI: 10.1097/01.MIB.0000442680.47427.bf     Document Type: Review

References (70)

1. Nathan C. Points of control in inflammation. Nature. 2002;420:846-852.
2. Targan SR, Hanauer SB, van Deventer SJ, et al. 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.
3. Danese S, Colombel JF, Reinisch W, et al. Review article: infliximab for Crohn's disease treatment-shifting therapeutic strategies after 10 years of clinical experience. Aliment Pharmacol Ther. 2011;33:857-869.
4. Lichtenstein GR. Comprehensive review: antitumor necrosis factor agents in inflammatory bowel disease and factors implicated in treatment response. Therap Adv Gastroenterol. 2013;6:269-293.
5. Nash PT, Florin TH. Tumour necrosis factor inhibitors. Med J Aust. 2005; 183:205-208.
6. Colombel JF, Sandborn WJ, Reinisch W, et al; SONIC Study Group. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010;362:1383-1395.
7. D'Haens GR, Panaccione R, Higgins PD, et al. 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.
8. Rutgeerts P, D'Haens G, Targan S, 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.
9. 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; 348:601-608.
10. Hanauer SB. Risks and benefits of combining immunosuppressives and biological agents in inflammatory bowel disease: is the synergy worth the risk? Gut. 2007;56:1181-1183.
11. Louis E, Mary JY, Vernier-Massouille G, et al. Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology. 2012;142:63-70.
12. Waugh AW, Garg S, Matic K, et al. Maintenance of clinical benefit in Crohn's disease patients after discontinuation of infliximab: long-term follow-up of a single centre cohort. Aliment Pharmacol Ther. 2010;32: 1129-1134.
13. Steenholdt C, Molazahi A, Ainsworth MA, et al. Outcome after discontinuation of infliximab in patients with inflammatory bowel disease in clinical remission: an observational Danish single center study. Scand J Gastroenterol. 2012;47:518-527.
14. Rismo R, Olsen T, Cui G, et al. Normalization of mucosal cytokine gene expression levels predicts long-term remission after discontinuation of anti-TNF therapy in Crohn's disease. Scand J Gastroenterol. 2013;48: 311-319.
15. Molnár T, Lakatos PL, Farkas K, et al. Predictors of relapse in patients with Crohn's disease in remission after 1 year of biological therapy. Aliment Pharmacol Ther. 2013;37:225-233.
16. Farkas K, Lakatos PL, Nagy F, et al. Predictors of relapse in patients with ulcerative colitis in remission after one-year of infliximab therapy. Scand J Gastroenterol. 2013;48:1394-1398.
17. Schnitzler F, Fidder H, Ferrante M, et al. Long-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a singlecentre cohort. Gut. 2009;58:492-500.
18. 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 randomised trial. Lancet. 2008;371:660-667.
19. Baert F, Moortgat L, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. Gastroenterology. 2010;138:463-468.
20. Sorrentino D, Paviotti A, Terrosu G, et al. Low dose maintenance therapy with infliximab prevents postsurgical recurrence of Crohn's disease. Clin Gastroenterol Hepatol. 2010;8:591-599.
21. Regueiro M, Kip KE, Schraut WH, et al. 4.5 Yr follow-up of patients enrolled in the randomized controlled trial (RCT) of infliximab (Inf) for prevention of postoperative Crohn's Disease (CD). Gastroenterology. 2010;138:S694.
22. Sorrentino D, Radford-Smith G. Maintenance of remission after stopping infliximab in Crohn's disease. Is all that glitters true gold? Gastroenterology. 2012;142:17-19.
23. De Suray N, Salleron J, Vernier-Massouille G, et al. Close monitoring of CRP and fecal calprotectin is able to predict clinical relapse in patients with Crohn's disease in remission after infliximab withdrawal. A subanalysis of the Stori study. Gastroenterology. 2012;142:S-149.
24. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, 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. 2008;58:S126-S135.
25. Felson DT, Smolen JS, Wells G, et al; American College of Rheumatology; European League Against Rheumatism. American College of Rheumatology/ European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 2011; 63:573-586.
26. Felson DT, Smolen JS, Wells G, et al. American College of Rheumatology/ European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis. 2011;70:404-413.
27. Frey O, Reichel A, Bonhagen K, et al. Regulatory T cells control the transition from acute into chronic inflammation in glucose-6-phosphate isomerase-induced arthritis. Ann Rheum Dis. 2010;69:1511-1518.
28. Saleem B, Keen H, Goeb V, et al. Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped? Ann Rheum Dis. 2010;69:1636-1642.
29. Harry RA, Anderson AE, Isaacs JD, et al. Generation and characterisation of therapeutic tolerogenic dendritic cells for rheumatoid arthritis. Ann Rheum Dis. 2010;69:2042-2050.
30. Roord ST, de Jager W, Boon L, et al. Autologous bone marrow transplantation in autoimmune arthritis restores immune homeostasis through CD4+CD25+Foxp3+ regulatory T cells. Blood. 2008;111:5233-5241.
31. Radbruch A, Thiel A. Cell therapy for autoimmune diseases: does it have a future? Ann Rheum Dis. 2004;63(suppl 2):ii96-ii101.
32. Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003;3:521-533.
33. Barnes MJ, Powrie F. Regulatory T cells reinforce intestinal homeostasis. Immunity. 2009;31:401-411.
34. Sartor RB. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390-407.
35. Itoh J, de La Motte C, Strong SA, et al. Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease. Gut. 2001;49:35-39.
36. Van den Brande JM, Braat H, van den Brink GR, et al. Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Gastroenterology. 2003;124:1774-1785.
37. Peake ST, Bernardo D, Peake ST, et al. Mechanisms of action of antitumor necrosis factor a agents in Crohn's disease. Inflamm Bowel Dis. 2013;19:1546-1555.
38. Danese S. Mechanisms of action of infliximab in inflammatory bowel disease: an anti-inflammatory multitasker. Dig Liver Dis. 2008;40:S225-S228.
39. Hölttä V, Sipponen T, Westerholm-Ormio M, et al. In Crohn's disease, anti-TNF-a treatment changes the balance between mucosal IL-17, FOXP3, and CD4 Cells. ISRN Gastroenterol. 2012;2012:505432.
40. Suenaert P, Bulteel V, Lemmens L, et al. Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease. Am J Gastroenterol. 2002;97:2000-2004.
41. Di Sabatino A, Pender SL, Jackson CL, et al. Functional modulation of Crohn's disease myofibroblasts by anti-tumor necrosis factor antibodies. Gastroenterology. 2007;133:137-149.
42. Di Sabatino A, Biancheri P, Piconese S, et al. Peripheral regulatory T cells and serum transforming growth factor-b: relationship with clinical response to infliximab in Crohn's disease. Inflamm Bowel Dis. 2010;16: 1891-1897.
43. Frøslie KF, Jahnsen J, Moum BA, et al. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133:412-422.
44. Ha C, Kornbluth A. Mucosal healing in inflammatory bowel disease: where do we stand? Curr Gastroenterol Rep. 2010;12:471-478.
45. 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;18:2225-2231.
46. Liu C, Xia X, Wu W, et al. Anti-tumour necrosis factor therapy enhances mucosal healing through down-regulation of interleukin-21 expression and T helper type 17 cell infiltration in Crohn's disease. Clin Exp Immunol. 2013;173:102-111.
47. McLeod RS, Wolff BG, Steinhart AH, et al. Risk and significance of endoscopic/radiological evidence of recurrent Crohn's disease. Gastroenterology. 1997;113:1823-1827.
48. Benevento G, Avellini C, Terrosu G, et al. Diagnosis and assessment of Crohn's disease: the present and the future. Expert Rev Gastroenterol Hepatol. 2010;4:757-766.
49. Munkholm P, Langholz E, Davidsen M, et al. Disease activity courses in a regional cohort of Crohn's disease patients. Scand J Gastroenterol. 1995;30:699-706.
50. Solberg IC, Vatn MH, Høie O, et al. Clinical course in Crohn's disease: results of a Norwegian population-based ten-year follow-up study. Clin Gastroenterol Hepatol. 2007;5:1430-1438.
51. Pariente B, Cosnes J, Danese S, et al. Development of the Crohn's disease digestive damage score, the Lémann score. Inflamm Bowel Dis. 2011;17: 1415-1422.
52. Andersen O. Disease mechanisms in multiple sclerosis: phases of disease improvement unrelated to relapses. Nat Rev Neurol. 2012;8:596-598.
53. Gisbert JP, Panés J. Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review. Am J Gastroenterol. 2009; 104:760-767.
54. Ordás I, Feagan BG, Sandborn WJ. Therapeutic drug monitoring of tumor necrosis factor antagonists in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2012;10:1079-1087.
55. REMICADE (infliximab) Prescribing Information 2012. Available at: www.remicade.com. Accessed November 5, 2013.
56. Hanauer SB, Feagan BG, Lichtenstein GR, et al; ACCENT I Study Group. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002;359:1541-1549.
57. Peyrin-Biroulet L, Bigard MA, Malesci A, et al. Step-up and top-down approaches to the treatment of Crohn's disease: early may already be too late. Gastroenterology. 2008;135:1420-1422.
58. Jois RN, Leeder J, Gibb A, et al. Low-dose infliximab treatment for ankylosing spondylitis-clinically- and cost-effective. Rheumatology. 2006;45:1566-1569.
59. van den Bemt BJF, den Broeder AA, Snijders GF, et al. Sustained effect after lowering high-dose infliximab in patients with rheumatoid arthritis: a prospective dose titration study. Ann Rheum Dis. 2008;67:1697-1701.
60. Beniwal P, Harrell L. The status of diagnostic markers for inflammatory bowel disease. Curr Gastroenterol Rep. 2010;12:479-484.
61. Ordás I, Mould DR, Feagan BG, et al. Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms. Clin Pharmacol Ther. 2012;91:635-646.
62. Sorrentino D, Hauenstein S, Marino M, et al. Low dose infliximab for prevention of postoperative recurrence of Crohn's disease: long term follow-up and impact of infliximab trough levels and antibodies to infliximab. Gastroenterology. 2013;144:S-777.
63. 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;46:310-318.
64. Cassinotti A, Travis S. Incidence and clinical significance of immunogenicity to infliximab in Crohn's disease: a critical systematic review. Inflamm Bowel Dis. 2009;15:1264-1275.
65. Sorrentino D. State of the art medical prevention of post-operative Crohn's disease. Nat Rev Gastroenterol Hepatol. 2013;10:413-422.
66. Andrews JM. Commentary: predicting relapse in Crohn's disease patients in remission with biologics. Aliment Pharmacol Ther. 2013;37: 497-498.
67. Peyrin-Biroulet L, Danese S. Stopping infliximab in Crohn's disease: still an ongoing STORI. Inflamm Bowel Dis. 2012;18:2201-2202.
68. Clarke K, Regueiro M. Stopping immunomodulators and biologics in inflammatory bowel disease patients in remission. Inflamm Bowel Dis. 2012;18:174-179.
69. Hashash JG, Regueiro MD. The great debate: stopping immunomodulators and biologics in Crohn's disease patients in remission. Expert Rev Gastroenterol Hepatol. 2013;7:501-503.
70. Pittet V, Froehlich F, Maillard MH, et al. When do we dare to stop biological or immunomodulatory therapy for Crohn's disease? Results of a multidisciplinary European expert panel. J Crohns Colitis. 2013;7: 820-826.