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Gastroenterology Research and Practice
Volume 2015 (2015), Article ID 832395, 18 pages
http://dx.doi.org/10.1155/2015/832395
Review Article

Optimal Endpoint of Therapy in IBD: An Update on Factors Determining a Successful Drug Withdrawal

First Department of Medicine, University of Szeged, Szeged 6720, Hungary

Received 15 April 2015; Accepted 27 May 2015

Academic Editor: Valérie Pittet

Copyright © 2015 Anita Annaházi and Tamás Molnár. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Burisch, “Crohn's disease and ulcerative colitis: occurrence, course and prognosis during the first year of disease in a European population-based inception cohort,” Danish Medical Journal, vol. 61, no. 1, p. B4778, 2014. View at Google Scholar · View at Scopus
  2. N. Svartz, “Salazopyrin, a new sulfanilamide preparation. A. Therapeutic Results in Rheumatic Polyarthritis. B. Therapeutic Results in Ulcerative Colitis. C. Toxic Manifestations in Treatment with Sulfanilamide Preparations,” Acta Medica Scandinavica, vol. 110, no. 6, pp. 577–598, 1942. View at Publisher · View at Google Scholar
  3. P. Miner Jr., S. Hanauer, M. Robinson, J. Schwartz, and S. Arora, “Safety and efficacy of controlled-release mesalamine for maintenance of remission in ulcerative colitis. Pentasa UC Maintenance Study Group,” Digestive Diseases and Sciences, vol. 40, no. 2, pp. 296–304, 1995. View at Publisher · View at Google Scholar · View at Scopus
  4. S. B. Hanauer, C. A. Sninsky, M. Robinson et al., “An oral preparation of mesalamine as long-term maintenance therapy for ulcerative colitis: a randomized, placebo-controlled trial,” Annals of Internal Medicine, vol. 124, no. 2, pp. 204–211, 1996. View at Publisher · View at Google Scholar
  5. J. P. Wright, E. A. O'Keefe, L. Cumming, and K. Jaskiewicz, “Olsalazine in maintenance of clinical remission in patients with ulcerative colsitis,” Digestive Diseases and Sciences, vol. 38, no. 10, pp. 1837–1842, 1993. View at Publisher · View at Google Scholar · View at Scopus
  6. G. Bresci, G. Parisi, and A. Capria, “Duration of remission and long-term prognosis according to the extent of disease in patients with ulcerative colitis on continuous mesalamine treatment,” Colorectal Disease, vol. 10, no. 8, pp. 814–817, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. A. K. Akobeng and E. Gardener, “Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn's disease,” Cochrane Database of Systematic Reviews, no. 1, Article ID CD003715, 2005. View at Google Scholar · View at Scopus
  8. A. Dignass, G. Van Assche, J. O. Lindsay et al., “The second European evidence-based consensus on the diagnosis and management of Crohn's disease: current management,” Journal of Crohn's and Colitis, vol. 4, no. 1, pp. 28–62, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. P. Riis, P. Anthonisen, H. R. Wulff, O. Folkenborg, O. Bonnevie, and V. Binder, “The prophylactic effect of salazosulphapyridine in ulcerative colitis during long-term treatment. A double-blind trial on patients asymptomatic for one year.,” Scandinavian Journal of Gastroenterology, vol. 8, no. 1, pp. 71–74, 1973. View at Google Scholar · View at Scopus
  10. A. S. Dissanayake and S. C. Truelove, “A controlled therapeutic trial of long term maintenance treatment of ulcerative colitis with sulphasalazine (Salazopyrin),” Gut, vol. 14, no. 12, pp. 923–926, 1973. View at Publisher · View at Google Scholar · View at Scopus
  11. S. Ardizzone, M. Petrillo, V. Imbesi, R. Cerutti, S. Bollani, and G. B. Porro, “Is maintenance therapy always necessary for patients with ulcerative colitis in remission?” Alimentary Pharmacology and Therapeutics, vol. 13, no. 3, pp. 373–379, 1999. View at Publisher · View at Google Scholar · View at Scopus
  12. A. B. Hawthorne, R. F. A. Logan, C. J. Hawkey et al., “Randomised controlled trial of azathioprine withdrawal in ulcerative colitis,” The British Medical Journal, vol. 305, no. 6844, pp. 20–22, 1992. View at Publisher · View at Google Scholar · View at Scopus
  13. D. P. O'Donoghue, A. M. Dawson, J. Powell-Tuck, R. L. Bown, and J. E. Lennard-Jones, “Double-blind withdrawal trial of azathioprine as maintenance treatment for Crohn's disease,” The Lancet, vol. 2, no. 8097, pp. 955–957, 1978. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Vilien, J. F. Dahlerup, L. K. Munck, P. Nørregaard, K. Grønbæk, and J. Fallingborg, “Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year,” Alimentary Pharmacology and Therapeutics, vol. 19, no. 11, pp. 1147–1152, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Lémann, J.-Y. Mary, J.-F. Colombel et al., “A randomized, double-blind, controlled withdrawal trial in Crohn's disease patients in long-term remission on azathioprine,” Gastroenterology, vol. 128, no. 7, pp. 1812–1818, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. Y. Bouhnik, M. Lémann, J.-Y. Mary et al., “Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine,” The Lancet, vol. 347, no. 8996, pp. 215–219, 1996. View at Publisher · View at Google Scholar · View at Scopus
  17. G. J. Mantzaris, A. Roussos, A. Christidou et al., “The long-term efficacy of azathioprine does not wane after four years of continuous treatment in patients with steroid-dependent luminal Crohn's disease,” Journal of Crohn's and Colitis, vol. 1, no. 1, pp. 28–34, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. X. Treton, Y. Bouhnik, J.-Y. Mary et al., “Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse,” Clinical Gastroenterology and Hepatology, vol. 7, no. 1, pp. 80–85, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. A. G. Fraser, D. Morton, D. McGovern, S. Travis, and D. P. Jewell, “The efficacy of methotrexate for maintaining remission in inflammatory bowel disease,” Alimentary Pharmacology & Therapeutics, vol. 16, no. 4, pp. 693–697, 2002. View at Publisher · View at Google Scholar · View at Scopus
  20. E. Domènech, J. Hinojosa, P. Nos et al., “Clinical evolution of luminal and perianal Crohn's disease after inducing remission with infliximab: how long should patients be treated?” Alimentary Pharmacology and Therapeutics, vol. 22, no. 11-12, pp. 1107–1113, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. F. Schnitzler, H. Fidder, M. Ferrante et al., “Long-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort,” Gut, vol. 58, no. 4, pp. 492–500, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. E. Louis, J.-Y. Mary, G. Verniermassouille et al., “Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped,” Gastroenterology, vol. 142, no. 1, pp. 63–70.e5, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. T. Molnár, P. L. Lakatos, K. Farkas et al., “Predictors of relapse in patients with Crohn's disease in remission after 1 year of biological therapy,” Alimentary Pharmacology and Therapeutics, vol. 37, no. 2, pp. 225–233, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. K. Farkas, P. L. Lakatos, F. Nagy et al., “Predictors of relapse in patients with ulcerative colitis in remission after one-year of infliximab therapy,” Scandinavian Journal of Gastroenterology, vol. 48, no. 12, pp. 1394–1398, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. J. George, D. H. Present, R. Pou, C. Bodian, and P. H. Rubin, “The long-term outcome of ulcerative colitis treated with 6-mercaptopurine,” The American Journal of Gastroenterology, vol. 91, no. 9, pp. 1711–1714, 1996. View at Google Scholar · View at Scopus
  26. A. G. Fraser, T. R. Orchard, and D. P. Jewell, “The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review,” Gut, vol. 50, no. 4, pp. 485–489, 2002. View at Publisher · View at Google Scholar · View at Scopus
  27. A. Cassinotti, G. C. Actis, P. Duca et al., “Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal,” American Journal of Gastroenterology, vol. 104, no. 11, pp. 2760–2767, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. P. S. Kim, J. Zlatanic, B. I. Korelitz, and G. W. Gleim, “Optimum duration of treatment with 6-mercaptopurine for Crohn's disease,” The American Journal of Gastroenterology, vol. 94, no. 11, pp. 3254–3257, 1999. View at Publisher · View at Google Scholar · View at Scopus
  29. M. H. Holtmann, F. Krummenauer, C. Claas et al., “Long-term effectiveness of azathioprine in IBD beyond 4 years: a european multicenter study in 1176 patients,” Digestive Diseases and Sciences, vol. 51, no. 9, pp. 1516–1524, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. C. Steenholdt, A. Molazahi, M. A. Ainsworth, J. Brynskov, O. Ø. Thomsen, and J. B. Seidelin, “Outcome after discontinuation of infliximab in patients with inflammatory bowel disease in clinical remission: an observational Danish single center study,” Scandinavian Journal of Gastroenterology, vol. 47, no. 5, pp. 518–527, 2012. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Farkas, P. L. Lakatos, M. Szucs et al., “Frequency and prognostic role of mucosal healing in patients with Crohn's disease and ulcerative colitis after one-year of biological therapy,” World Journal of Gastroenterology, vol. 20, no. 11, pp. 2995–3001, 2014. View at Publisher · View at Google Scholar · View at Scopus
  32. A. W. G. Waugh, S. Garg, K. Matic et al., “Maintenance of clinical benefit in Crohn's disease patients after discontinuation of infliximab: long-term follow-up of a single centre cohort,” Alimentary Pharmacology and Therapeutics, vol. 32, no. 9, pp. 1129–1134, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. P. Fockens, C. J. J. Mulder, G. N. J. Tytgat et al., “Comparison of the efficacy and safety of 1.5 compared with 3.0 g oral slow-release mesalazine (Pentasa) in the maintenance treatment of ulcerative colitis,” European Journal of Gastroenterology and Hepatology, vol. 7, no. 11, pp. 1025–1030, 1995. View at Publisher · View at Google Scholar · View at Scopus
  34. S. Ardizzone and G. B. Porro, “How long is it advisable to prolong maintenance treatment of patients with ulcerative colitis?” Inflammatory bowel diseases, vol. 14, supplement 2, pp. S238–S239, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. G. Bardazzi, G. D'Albasio, A. Bonanomi et al., “Intermittent versus continuous 5-aminosalicylic acid treatment for maintaining remission in ulcerative colitis,” Italian Journal of Gastroenterology, vol. 26, no. 7, pp. 334–337, 1994. View at Google Scholar · View at Scopus
  36. R. J. Dickinson, A. King, D. G. D. Wight, J. O. Hunter, and G. Neale, “Is continuous sulfasalazine necessary in the management of patients with ulcerative colitis? Results of a preliminary study,” Diseases of the Colon & Rectum, vol. 28, no. 12, pp. 929–930, 1985. View at Publisher · View at Google Scholar · View at Scopus
  37. T. Moshkovska and J. F. Mayberry, “Duration of treatment with 5-aminosalicylic acid compounds,” World Journal of Gastroenterology, vol. 13, no. 32, pp. 4310–4315, 2007. View at Google Scholar · View at Scopus
  38. K. W. Schroeder, “Review: is mesalamine safe?” Gastroenterology and Hepatology, vol. 3, no. 11, pp. 878–879, 2007. View at Google Scholar · View at Scopus
  39. J. H. Baron, A. M. Connell, J. E. Lennard-Jones, and F. Avery Jones, “Sulphasalazine and salicylazosulphadimidine in ulcerative colitis,” The Lancet, vol. 279, no. 7239, pp. 1094–1096, 1962. View at Publisher · View at Google Scholar · View at Scopus
  40. A. P. Dick, M. J. Grayson, R. G. Carpenter, and A. Petrie, “Controlled trial of sulphasalazine in the treatment of ulcerative colitis,” Gut, vol. 5, pp. 437–442, 1964. View at Publisher · View at Google Scholar · View at Scopus
  41. A. C. Moss and M. A. Peppercorn, “The risks and the benefits of mesalazine as a treatment for ulcerative colitis,” Expert Opinion on Drug Safety, vol. 6, no. 2, pp. 99–107, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. E. V. Loftus Jr., S. V. Kane, and D. Bjorkman, “Systematic review: short-term adverse effects of 5-aminosalicylic acid agents in the treatment of ulcerative colitis,” Alimentary Pharmacology and Therapeutics, vol. 19, no. 2, pp. 179–189, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Ham and A. C. Moss, “Mesalamine in the treatment and maintenance of remission of ulcerative colitis,” Expert Review of Clinical Pharmacology, vol. 5, no. 2, pp. 113–123, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. G. R. Lichtenstein, A. C. Barrett, E. Bortey, C. Paterson, and W. P. Forbes, “Long-term safety and tolerability of once-daily mesalamine granules in the maintenance of remission of ulcerative colitis,” Inflammatory Bowel Diseases, vol. 20, no. 8, pp. 1399–1406, 2014. View at Publisher · View at Google Scholar
  45. D. H. Present, B. I. Korelitz, N. Wisch, J. L. Glass, D. B. Sachar, and B. S. Pasternack, “Treatment of Crohn's disease with 6-mercaptopurine. A long-term, randomized, double-blind study,” The New England Journal of Medicine, vol. 302, no. 18, pp. 981–987, 1980. View at Publisher · View at Google Scholar · View at Scopus
  46. N. Chande, D. J. Tsoulis, and J. K. MacDonald, “Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease,” The Cochrane Database of Systematic Reviews, vol. 4, Article ID CD000545, 2013. View at Google Scholar · View at Scopus
  47. S. Candy, J. Wright, M. Gerber, G. Adams, M. Gerig, and R. Goodman, “A controlled double blind study of azathioprine in the management of Crohn's disease,” Gut, vol. 37, no. 5, pp. 674–678, 1995. View at Publisher · View at Google Scholar · View at Scopus
  48. D. C. Pearson, G. R. May, G. Fick et al., “Azathioprine for maintaining remission of Crohn's disease,” Cochrane Database of Systematic Reviews, no. 2, Article ID CD000067, 2000. View at Google Scholar
  49. J. P. Gisbert, P. M. Linares, A. G. McNicholl, J. Mate, and F. Gomollon, “Meta-analysis: the efficacy of azathioprine and mercaptopurine in ulcerative colitis,” Alimentary Pharmacology and Therapeutics, vol. 30, no. 2, pp. 126–137, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. A. Timmer, J. W. McDonald, D. J. Tsoulis, and J. K. Macdonald, “Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis,” The Cochrane Database of Systematic Reviews, vol. 9, Article ID CD000478, 2012. View at Publisher · View at Google Scholar
  51. A. Dignass, J. O. Lindsay, A. Sturm et al., “Second European evidence-based consensus on the diagnosis and management of ulcerative colitis. Part 2. current management,” Journal of Crohn's and Colitis, vol. 6, no. 10, pp. 991–1030, 2012. View at Publisher · View at Google Scholar · View at Scopus
  52. X. Roblin, F. Serre-Debeauvais, J.-M. Phelip et al., “6-tioguanine monitoring in steroid-dependent patients with inflammatory bowel diseases receiving azathioprine,” Alimentary Pharmacology and Therapeutics, vol. 21, no. 7, pp. 829–839, 2005. View at Publisher · View at Google Scholar · View at Scopus
  53. F. Bär, C. Sina, and K. Fellermann, “Thiopurines in inflammatory bowel disease revisited,” World Journal of Gastroenterology, vol. 19, no. 11, pp. 1699–1706, 2013. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Konidari and W. E. Matary, “Use of thiopurines in inflammatory bowel disease: safety issues,” The World Journal of Gastrointestinal Pharmacology and Therapeutics, vol. 5, pp. 63–76, 2014. View at Google Scholar
  55. W. R. Connell, M. A. Kamm, J. K. Ritchie, and J. E. Lennard-Jones, “Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience,” Gut, vol. 34, no. 8, pp. 1081–1085, 1993. View at Publisher · View at Google Scholar · View at Scopus
  56. M. Toruner, E. V. Loftus Jr., W. S. Harmsen et al., “Risk factors for opportunistic infections in patients with inflammatory bowel disease,” Gastroenterology, vol. 134, no. 4, pp. 929–936, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. R. Brem, F. Li, and P. Karran, “Reactive oxygen species generated by thiopurine/UVA cause irreparable transcription-blocking DNA lesions,” Nucleic Acids Research, vol. 37, no. 6, pp. 1951–1961, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. M. D. Long, H. H. Herfarth, C. A. Pipkin, C. Q. Porter, R. S. Sandler, and M. D. Kappelman, “Increased risk for non-melanoma skin cancer in patients with inflammatory bowel disease,” Clinical Gastroenterology and Hepatology, vol. 8, no. 3, pp. 268–274, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. A. Kandiel, A. G. Fraser, B. I. Korelitz, C. Brensinger, and J. D. Lewis, “Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine,” Gut, vol. 54, no. 8, pp. 1121–1125, 2005. View at Publisher · View at Google Scholar · View at Scopus
  60. L. Beaugerie, N. Brousse, A. M. Bouvier et al., “Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study,” The Lancet, vol. 374, no. 9701, pp. 1617–1625, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. N. Khan, A. M. Abbas, G. R. Lichtenstein, E. V. Loftus Jr., and L. A. Bazzano, “Risk of lymphoma in patients with ulcerative colitis treated with thiopurines: a nationwide retrospective cohort study,” Gastroenterology, vol. 145, no. 5, pp. 1007–1015.e3, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. C. W. Lees, J. Critchley, N. Chee et al., “Lack of association between cervical dysplasia and IBD: a large case-control study,” Inflammatory Bowel Diseases, vol. 15, no. 11, pp. 1621–1629, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. W. R. Connell, M. A. Kamm, M. Dickson, A. M. Balkwill, J. K. Ritchie, and J. E. Lennard-Jones, “Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease,” The Lancet, vol. 343, no. 8908, pp. 1249–1252, 1994. View at Publisher · View at Google Scholar · View at Scopus
  64. Y. Masunaga, K. Ohno, R. Ogawa, M. Hashiguchi, H. Echizen, and H. Ogata, “Meta-analysis of risk of malignancy with immunosuppressive drugs in inflammatory bowel disease,” Annals of Pharmacotherapy, vol. 41, no. 1, pp. 21–28, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. V. Patel, Y. Wang, J. K. MacDonald, J. W. McDonald, and N. Chande, “Methotrexate for maintenance of remission in Crohn's disease,” The Cochrane Database of Systematic Reviews, vol. 8, Article ID CD006884, 2014. View at Publisher · View at Google Scholar
  66. M. Lémann, T. Zenjari, Y. Bouhnik et al., “Methotrexate in Crohn's disease: long-term efficacy and toxicity,” The American Journal of Gastroenterology, vol. 95, no. 7, pp. 1730–1734, 2000. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Mañosa, V. García, L. Castro et al., “Methotrexate in ulcerative colitis: a Spanish multicentric study on clinical use and efficacy,” Journal of Crohn's and Colitis, vol. 5, no. 5, pp. 397–401, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Sosin and S. Handa, “Low dose methotrexate and bone marrow suppression,” British Medical Journal, vol. 326, no. 7383, pp. 266–267, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. N. Khan, A. M. Abbas, N. Whang, L. A. Balart, L. A. Bazzano, and T. N. Kelly, “Incidence of liver toxicity in inflammatory bowel disease patients treated with methotrexate: a meta-analysis of clinical trials,” Inflammatory Bowel Diseases, vol. 18, no. 2, pp. 359–367, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. P. L. Valentino, P. C. Church, P. S. Shah et al., “Hepatotoxicity caused by methotrexate therapy in children with inflammatory bowel disease: a systematic review and meta-analysis,” Inflammatory Bowel Diseases, vol. 20, no. 1, pp. 47–59, 2014. View at Publisher · View at Google Scholar · View at Scopus
  71. P. Barrera, R. F. J. M. Laan, P. L. C. M. van Riel, P. N. R. Dekhuijzen, A. M. T. Boerbooms, and L. B. A. van de Putte, “Methotrexate-related pulmonary complications in rheumatoid arthritis,” Annals of the Rheumatic Diseases, vol. 53, no. 7, pp. 434–439, 1994. View at Publisher · View at Google Scholar · View at Scopus
  72. A. G. Fraser, “Methotrexate: first-line or second-line immunomodulator?” European Journal of Gastroenterology and Hepatology, vol. 15, no. 3, pp. 225–231, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Ferrante, S. Vermeire, H. Fidder et al., “Long-term outcome after infliximab for refractory ulcerative colitis,” Journal of Crohn's and Colitis, vol. 2, no. 3, pp. 219–225, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. B. W. Behm and S. J. Bickston, “Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn's disease,” Cochrane Database of Systematic Reviews, no. 1, Article ID CD006893, 2008. View at Google Scholar · View at Scopus
  75. W. J. Sandborn, G. van Assche, W. Reinisch et al., “Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis,” Gastroenterology, vol. 142, no. 2, pp. 257–265.e3, 2012. View at Publisher · View at Google Scholar · View at Scopus
  76. J.-F. Colombel, W. J. Sandborn, P. Rutgeerts et al., “Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial,” Gastroenterology, vol. 132, no. 1, pp. 52–65, 2007. View at Publisher · View at Google Scholar · View at Scopus
  77. W. J. Sandborn, S. B. Hanauer, P. Rutgeerts et al., “Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial,” Gut, vol. 56, no. 9, pp. 1232–1239, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. R. Caviglia, M. Ribolsi, M. Rizzi, S. Emerenziani, M. L. Annunziata, and M. Cicala, “Maintenance of remission with infliximab in inflammatory bowel disease: efficacy and safety long-term follow-up,” World Journal of Gastroenterology, vol. 13, no. 39, pp. 5238–5244, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. J. P. Gisbert and J. Panés, “Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review,” The American Journal of Gastroenterology, vol. 104, no. 3, pp. 760–767, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. J. F. Colombel, W. J. Sandborn, S. Ghosh et al., “Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: data from ULTRA 1, 2, and 3,” The American Journal of Gastroenterology, vol. 109, no. 11, pp. 1771–1780, 2014. View at Publisher · View at Google Scholar
  81. D. Sorrentino and G. Radford-Smith, “Clinical remission after stopping infliximab in Crohn's Disease: is all that glitters true gold?” Gastroenterology, vol. 142, no. 5, article e17, 2012. View at Publisher · View at Google Scholar · View at Scopus
  82. G. R. Lichtenstein, B. G. Feagan, R. D. Cohen et al., “Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry,” Clinical Gastroenterology and Hepatology, vol. 4, no. 5, pp. 621–630, 2006. View at Publisher · View at Google Scholar · View at Scopus
  83. H. Fidder, F. Schnitzler, M. Ferrante et al., “Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study,” Gut, vol. 58, no. 4, pp. 501–508, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. W. S. Mow, M. T. Abreu-Martin, K. A. Papadakis, H. E. Pitchon, S. R. Targan, and E. A. Vasiliauskas, “High incidence of anergy in inflammatory bowel disease patients limits the usefulness of PPD screening before infliximab therapy,” Clinical Gastroenterology and Hepatology, vol. 2, no. 4, pp. 309–313, 2004. View at Publisher · View at Google Scholar · View at Scopus
  85. C. J. M. Williams, L. Peyrin-Biroulet, and A. C. Ford, “Systematic review with meta-analysis: malignancies with anti-tumour necrosis factor-α therapy in inflammatory bowel disease,” Alimentary Pharmacology and Therapeutics, vol. 39, no. 5, pp. 447–458, 2014. View at Publisher · View at Google Scholar · View at Scopus
  86. A. Theibich, L. Dreyer, M. Magyari, and H. Locht, “Demyelinizing neurological disease after treatment with tumor necrosis factor alpha-inhibiting agents in a rheumatological outpatient clinic: description of six cases,” Clinical Rheumatology, vol. 33, no. 5, pp. 719–723, 2014. View at Publisher · View at Google Scholar · View at Scopus
  87. S. Mazzuoli, F. W. Guglielmi, E. Antonelli, M. Salemme, G. Bassotti, and V. Villanacci, “Definition and evaluation of mucosal healing in clinical practice,” Digestive and Liver Disease, vol. 45, no. 12, pp. 969–977, 2013. View at Publisher · View at Google Scholar · View at Scopus
  88. R. Bryant, S. Winer, T. Spl, and R. Riddell, “Systematic review: histological remission in inflammatory bowel disease. Is ‘complete’ remission the new treatment paradigm? An IOIBD initiative,” Journal of Crohn's and Colitis, vol. 8, no. 12, pp. 1582–1597, 2014. View at Publisher · View at Google Scholar
  89. G. J. Devroede, W. F. Taylor, W. G. Sauer, R. J. Jackman, and G. B. Stickler, “Cancer risk and life expectancy of children with ulcerative colitis,” The New England Journal of Medicine, vol. 285, no. 1, pp. 17–21, 1971. View at Publisher · View at Google Scholar · View at Scopus
  90. E. Langholz, “Review: current trends in inflammatory bowel disease: the natural history,” Therapeutic Advances in Gastroenterology, vol. 3, no. 2, pp. 77–86, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. C. Canavan, K. R. Abrams, and J. Mayberry, “Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn's disease,” Alimentary Pharmacology & Therapeutics, vol. 23, no. 8, pp. 1097–1104, 2006. View at Publisher · View at Google Scholar · View at Scopus
  92. K. V. Winther, T. Jess, E. Langholz, P. Munkholm, and V. Binder, “Long-term risk of cancer in ulcerative colitis: a population-based cohort study from Copenhagen County,” Clinical Gastroenterology and Hepatology, vol. 2, no. 12, pp. 1088–1095, 2004. View at Publisher · View at Google Scholar · View at Scopus
  93. T. Jess, E. V. Loftus Jr., F. S. Velayos et al., “Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota,” Gastroenterology, vol. 130, no. 4, pp. 1039–1046, 2006. View at Publisher · View at Google Scholar · View at Scopus
  94. G. Margagnoni, C. Pagnini, F. Menasci, S. Festa, and G. D. Fave, “Critical review of the evidence on 5-aminosalicilate for chemoprevention of colorectal cancer in ulcerative colitis: a methodological question,” Current Clinical Pharmacology, vol. 9, no. 1, pp. 84–90, 2014. View at Publisher · View at Google Scholar · View at Scopus
  95. S. Sebastian, V. Hernández, P. Myrelid et al., “Colorectal cancer in inflammatory bowel disease: results of the 3rd ECCO pathogenesis scientific workshop (I),” Journal of Crohn's and Colitis, vol. 8, no. 1, pp. 5–18, 2014. View at Publisher · View at Google Scholar · View at Scopus
  96. U. Nieminen, A. Jussila, S. Nordling, H. Mustonen, and M. A. Färkkilä, “Inflammation and disease duration have a cumulative effect on the risk of dysplasia and carcinoma in IBD: a case-control observational study based on registry data,” International Journal of Cancer, vol. 134, no. 1, pp. 189–196, 2014. View at Publisher · View at Google Scholar · View at Scopus
  97. D. T. Rubin, D. Huo, J. A. Kinnucan et al., “Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study,” Clinical Gastroenterology and Hepatology, vol. 11, no. 12, pp. 1601–1608.e4, 2013. View at Publisher · View at Google Scholar · View at Scopus
  98. J. E. Baars, C. W. N. Looman, E. W. Steyerberg et al., “The risk of inflammatory bowel disease-related colorectal carcinoma is limited: results from a nationwide nested case-control study,” American Journal of Gastroenterology, vol. 106, no. 2, pp. 319–328, 2011. View at Publisher · View at Google Scholar · View at Scopus
  99. P. De Cruz, M. A. Kamm, L. Prideaux, P. B. Allen, and P. V. Desmond, “Postoperative recurrent luminal Crohn's disease: a systematic review,” Inflammatory Bowel Diseases, vol. 18, no. 4, pp. 758–777, 2012. View at Publisher · View at Google Scholar · View at Scopus
  100. J. Jones, R. Panaccione, M. L. Russell, and R. Hilsden, “Medical management of inflammatory bowel disease among Canadian gastroenterologists,” Canadian Journal of Gastroenterology, vol. 25, no. 10, pp. 565–569, 2011. View at Google Scholar · View at Scopus
  101. T. Molnár, K. Farkas, T. Nyári, F. Nagy, Z. Szepes, and T. Wittmann, “Every fourth patient with Crohn's disease has anti-TNF dependency,” Alimentary Pharmacology and Therapeutics, vol. 34, no. 3, pp. 400–401, 2011. View at Publisher · View at Google Scholar · View at Scopus
  102. C. Lu, A. Waugh, R. J. Bailey et al., “Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation,” World Journal of Gastroenterology, vol. 18, no. 36, pp. 5058–5064, 2012. View at Publisher · View at Google Scholar · View at Scopus