I. Ordas, B.G. Feagan, and W.J. Sandborn Early use of immunosuppressives or TNF antagonists for the treatment of Crohn's disease: time for a change Gut 60 2011 1754 1763
B.G. Levesque, W.J. Sandborn, J. Ruel, and et al. Converging goals of treatment of inflammatory bowel disease from clinical trials and practice Gastroenterology 148 2015 37 51.e1
J.F. Colombel, W.J. Sandborn, W. Reinisch, and et al. Infliximab, azathioprine, or combination therapy for Crohn's disease N Engl J Med 362 2010 1383 1395
R. Panaccione, S. Ghosh, S. Middleton, and et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis Gastroenterology 146 2014 392 400.e3
B. Pariente, J. Cosnes, S. Danese, and et al. Development of the Crohn's disease digestive damage score, the Lemann score Inflamm Bowel Dis 17 2011 1415 1422
Higgins JPT GSeCIHJ, and S. Green Chapter 8: assessing risk of bias in included studies. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 (updated March 2011) 2011 The Cochrane Collaboration http://www.cochranehandbook.org
Wells GA, Shea B, O'Connell D et al. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. http://www.ohri.ca/programs/clinical-epidemiology/oxford.asp. Accessed April 2015.
M. Lemann, J.Y. Mary, J.F. Colombel, and et al. A randomized, double-blind, controlled withdrawal trial in Crohn's disease patients in long-term remission on azathioprine Gastroenterology 128 2005 1812 1818
D.P. O'Donoghue, A.M. Dawson, and J. Powell-Tuck Double-blind withdrawal trial of azathioprine as maintenance treatment for Crohn's disease Lancet 2 1978 955 957
H.H. Wenzl, C. Primas, G. Novacek, and et al. Withdrawal of long-term maintenance treatment with azathioprine tends to increase relapse risk in patients with Crohn's disease Dig Dis Sci 60 2015 1414 1423
M. Vilien, J.F. Dahlerup, L.K. Munck, and et al. Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year Aliment Pharmacol Ther 19 2004 1147 1152
A.B. Hawthorne, R.F.A. Logan, C.J. Hawkey, and et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis BMJ 305 1992 20 22
J. George, D.H. Present, R. Pou, and et al. The long-term outcome of ulcerative colitis treated with 6-mercaptopurine Am J Gastroenterol 91 1996 1711 1714
Y. Bouhnik, M. Lemann, J.Y. Mary, and et al. Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine Lancet 347 1996 215 219
P.S. Kim, J. Zlatanic, B.I. Korelitz, and et al. Optimum duration of treatment with 6-mercaptopurine for Crohn's disease Am J Gastroenterol 94 1999 3254 3257
A.G. Fraser, D. Morton, D. McGovern, and et al. The efficacy of methotrexate for maintaining remission in inflammatory bowel disease Aliment Pharmacol Ther 16 2002 693 697
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 50 2002 485 489
E.Z. Lobel, B.I. Korelitz, M.A. Xuereb, and et al. A search for the optimal duration of treatment with 6-mercaptopurine for ulcerative colitis Am J Gastroenterol 99 2004 462 465
A. Cassinotti, G.C. Actis, P. Duca, and et al. Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal Am J Gastroenterol 104 2009 2760 2767
X. Treton, Y. Bouhnik, J. Mary, and et al. Azathioprine withdrawal in patients with crohn's disease maintained on prolonged remission: a high risk of relapse Clin Gastroenterol Hepatol 7 2009 80 85
C. Pratico, N. Capozzi, F. Rizzello, and et al. Prospective withdrawal trial of azathioprine (AZA) in ulcerative colitis (UC) (abstr) J Crohns Colitis 8 suppl 2014 S219 S220
E. Moreno-Rincón, F.J. Serrano-Ruiz, J.M. Benítez, and et al. Prognosis of patients with ulcerative colitis in remission after thiopurines withdrawal (abstr) J Crohns Colitis 9 suppl 1 2015 S355
Y. Qiu, R. Mao, B.I. Chen, and et al. Predictors of disease relapse of patients with Crohn's disease in deep remission: who and when can withdraw thiopurine maintenance therapy? (abstr) J Crohns Colitis 9 suppl 1 2015 S61
N.A. Kennedy, R. Kalla, B. Warner, and et al. Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients Aliment Pharmacol Ther 40 2014 1313 1323
H. Sokol, P. Seksik, I. Nion-Larmurier, and et al. Current smoking, not duration of remission, delays Crohn's disease relapse following azathioprine withdrawal Inflamm Bowel Dis 16 2010 362 363
G. Van Assche, C. Magdelaine-Beuzelin, G. D'Haens, and et al. Withdrawal of immunosuppression in Crohn's disease treated with scheduled infliximab maintenance: a randomized trial Gastroenterology 134 2008 1861 1868
J. Kierkus, B. Iwanczak, A. Wegner, and et al. Monotherapy with infliximab versus combination therapy in the maintenance of clinical remission in children with moderate to severe Crohn disease J Pediatr Gastroenterol Nutr 60 2015 580 585
H. Sokol, P. Seksik, I. Nion-Larmurier, and et al. Withdrawal of immunosuppression in inflammatory bowel disease treated with infliximab maintenance therapy (abstr) Gastroenterology 136 2009 A187 A188
D. Drobne, P. Bossuyt, C. Breynaert, and et al. Withdrawal of immunomodulators after co-treatment does not reduce trough level of infliximab in patients with Crohn's disease Clin Gastroenterol Hepatol 13 2015 514 521.e4
G.J. Choi, D.I. Park, J.H. Park, and et al. Withdrawal of azathioprine in luminal Crohn's disease treated with infliximab maintenance therapy: a retrospective case-control study (abstr) J Gastroenterol Hepatol 25 2010 A86
M. Fischer, S.C. Campbell, C.S. Johnson, and et al. Risk factors for rescue therapy in Crohn's patients on combination therapy after discontinuation of the immunomodulator (abstr) Gastroenterology 146 2014 S-450
A. Oussalah, J.B. Chevaux, R. Fay, and et al. Predictors of infliximab failure after azathioprine withdrawal in crohn's disease treated with combination therapy Am J Gastroenterol 105 2010 1142 1149
J. Filippi, D. Laharie, C. Michiels, and et al. Efficacy of sustained combination therapy for at least 6 months with thiopurines and infliximab in patients with ulcerative colitis in clinical remission: a retrospective multicenter French experience J Crohns Colitis 9 2015 252 258
G.J. Mantzaris, P. Karatzas, N. Kyriakos, and et al. Can we increase the dose interval of infliximab to 10 weeks without risking loss of response in patients with Crohn's disease? Prospective, single-center pilot study based on successive measurements of fecal calprotectin (abstr) Gastroenterology 146 2014 S-248
D. Sorrentino, A. Paviotti, G. Terrosu, and et al. Low-dose maintenance therapy with infliximab prevents postsurgical recurrence of Crohn's disease Clin Gastroenterol Hepatol 8 2010 591 599.e1
V. Ciria, P. Silva, E. Leo, and et al. Factors influencing recurrence following suspension of biological treatment. Importance of mucosal healing (abstr) J Crohns Colitis 8 suppl 2014 S270
A. Armuzzi, M. Marzo, C. Felice, and et al. Long-term scheduled therapy with infliximab in inflammatory bowel disease: a single-centre observational study (abstr) Gastroenterology 138 2010 S-691 S-692
C. Lane, S. Ramakrishnan, and J. Dougherty Outcomes of the use of infliximab and adalimumab in patients with Crohn's disease at a district general hospital (abstr) Gut 63 2014 A70
M. Iimuro, S. Nakamura, T. Sato, and et al. Long term outcome of top-down therapy in Crohn's disease: a single-center experience (abstr) Inflamm Bowel Dis 17 2011 S49 S50
E. Domenech, J. Hinojosa, P. Nos, and et al. Clinical evolution of luminal and perianal Crohn's disease after inducing remission with infliximab: how long should patients be treated? Aliment Pharmacol Ther 22 2005 1107 1113
A. Chauvin, A. Le Thuaut, M. Belhassan, and et al. Infliximab as a bridge to remission maintained by antimetabolite therapy in Crohn's disease: a retrospective study Dig Liver Dis 46 2014 695 700
J. Wynands, R. Belbouab, S. Candon, and et al. 12-month follow-up after successful infliximab therapy in pediatric crohn disease J Pediatr Gastroenterol Nutr 46 2008 293 298
T. Molnar, P.L. Lakatos, K. Farkas, and et al. Predictors of relapse in patients with Crohn's disease in remission after 1 year of biological therapy Aliment Pharmacol Ther 37 2013 225 233
T. Molnar, K. Farkas, P. Miheller, and et al. Is the efficacy of successful infliximab induction therapy maintained for one year lasting without retreatment in different behavior types of Crohn's disease? J Crohns Colitis 2 2008 322 326
V. Crombe, J. Salleron, G. Savoye, and et al. Long-term outcome of treatment with infliximab in pediatric-onset Crohn's disease: a population-based study Inflamm Bowel Dis 17 2011 2144 2152
F. Nuti, F. Conte, N. Cavallari, and et al. Long term efficacy of infliximab in inflammatory bowel disease at a single tertiary center Dig Liver Dis 42 2010 S326 S327
E. Louis, J.Y. Mary, G. Verniermassouille, and et al. Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped Gastroenterology 142 2012 63 70.e5
K. Papamichael, N. Vande Casteele, A. Gils, and et al. Long-term outcome of patients with Crohn's disease who discontinued infliximab therapy upon clinical remission Clin Gastroenterol Hepatol 13 2015 1103 1110
A.J. Brooks, S. Sebastian, S.S. Cross, and et al. Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn's disease in established remission J Crohns Colitis 2015 May 18 [Epub ahead of print]
R.J. Dart, N. Griffin, K. Taylor, and et al. Reassessment of Crohn' s disease treated with at least 12 months of anti-TNF therapy: how likely is treatment withdrawal? Frontline Gastroenterol 5 2014 176 182
R. Monterubbianesi, C. Papi, and A. Kohn Maintenance of clinical remission in Crohn's disease patients after discontinuation of antiTNF agents: results from a single centre cohort (abstr) J Crohns Colitis 9 suppl 1 2015 S345
C. Steenholdt, A. Molazahi, M.A. Ainsworth, and 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 47 2012 518 527
C. Dai, W.X. Liu, M. Jiang, and et al. Mucosal healing did not predict sustained clinical remission in patients with IBD after discontinuation of one-year infliximab therapy PLoS One 9 2014 e110797
N.A. Kennedy, B. Warner, E. Johnston, and et al. Anti-TNF withdrawal in IBD: Relapse and recapture rates and predictive factors from 160 patients in a pan-UK study (abstr) J Crohns Colitis 9 suppl 1 2015 S41 S42
M.J. Casanova, M. Chaparro, V. Garcia-Sanchez, and et al. Evolution after anti-TNF drug discontinuation in patients with inflammatory bowel disease (IBD): a multicenter long-term follow-up study (abstr) J Crohns Colitis 9 suppl 1 2015 S329
L. Ramos, A. Hernandez Camba, M. Carrillo Palau, and et al. Outcome of treatment with biological agents in Crohn's disease: 117 patients in 5 years from a tertiary referral center (abstr) J Crohns Colitis 8 suppl 2014 S231
D. Duricová, M. Bortlik, N. Machkova, and et al. Deep remission in Crohn's disease does not prevent disease relapse after withdrawal of anti-TNFa therapy (abstr) Gastroenterology 148 suppl 1 2015 S-61
I. Luppino, R. Spagnuolo, R. Marasco, and et al. Withdrawal of infliximab (IFX) after achieving remission: outcome in a cohort of inflammatory bowel disease (IBD) patients Dig Liver Dis 45 2013 S100 S101
E. Zucchi, M. Fabbro, E. Pinese, and et al. Outcome of infliximab discontinuation in IBD patients and therapy rechallenging in relapsers: single centre preliminary data Dig Liver Dis 46 2014 S31
A.W.G. Waugh, S. Garg, K. Matic, and 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 32 2010 1129 1134
F. Schnitzler, H. Fidder, M. Ferrante, and et al. Long-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort Gut 58 2009 492 500
A. Echarri, V. Ollero, J.A. Rodriguez, and et al. Predictors of relapse after discontinuing anti-TNF therapy in Crohn's disease patients on deep remission J Crohns Colitis 7 suppl 2013 S171
R. Rismo, T. Olsen, G. Cui, and 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 48 2013 311 319
P. Molander, M. Farkkila, K. Salminen, and et al. Outcome after discontinuation of TNFalpha-blocking therapy in patients with inflammatory bowel disease in deep remission Inflamm Bowel Dis 20 2014 1021 1028
N. De Suray, J. Salleron, G. Vernier-Massouille, and et al. Close monitoring of CRP and fecal calprotectin is able to predict clinical relapse in patients with crohn's disease in remission after infiximab withdrawal. A sub-analysis of the stori study Gastroenterology 142 suppl 1 2012 S-149
P. Molander, M. Farkkila, A. Ristimaki, and et al. Does fecal calprotectin predict short-term relapse after stopping TNFalpha-blocking agents in inflammatory bowel disease patients in deep remission? J Crohns Colitis 9 2015 33 40
G. Fanjiang, G.H. Russell, and A.J. Katz Short- and long-term response to and weaning from infliximab therapy in pediatric ulcerative colitis J Pediatr Gastroenterol Nutr 44 2007 312 317
C. Munoz Villafranca, M.T. Bravo Rodriguez, J. Ortiz De Zarate, and et al. Mucosal healing in patients with ulcerative colitis treated with infliximab. What happens after treatment is discontinued? J Crohns Colitis 8 suppl 2014 S234 S235
R. Caviglia, M. Ribolsi, M. Rizzi, and et al. Maintenance of remission with infliximab in inflammatory bowel disease: efficacy and safety long-term follow-up World J Gastroenterol 13 2007 5238 5244
K. Farkas, P.L. Lakatos, F. Nagy, and et al. Predictors of relapse in patients with ulcerative colitis in remission after one-year of infliximab therapy Scand J Gastroenterol 48 2013 1394 1398
K. Farkas, P.L. Lakatos, M. Szucs, and 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 J Gastroenterol 20 2014 2995 3001
Z. Zelinkova, C. van der Ent, K.F. Bruin, and et al. Effects of discontinuing anti-tumor necrosis factor therapy during pregnancy on the course of inflammatory bowel disease and neonatal exposure Clin Gastroenterol Hepatol 11 2013 318 321
A. de Lima, Z. Zelinkova, C. van der Ent, and et al. Tailored anti-TNF therapy during pregnancy in patients with IBD: maternal and fetal safety Gut 2015 May 12 [Epub ahead of print]
M. Seirafi, X. Treton, B. De Vroey, and et al. Anti-TNF therapy and pregnancy in inflammatory bowel disease: a prospective cohort study from the GETAID Gastroenterology 140 suppl 1 2011 S-175
D. Sorrentino, P. Nash, M. Viladomiu, and et al. Stopping anti-TNF agents in patients with Crohn's disease in remission: is it a feasible long-term strategy? Inflamm Bowel Dis 20 2014 757 766
K. Papamichael, and S. Vermeire Withdrawal of anti-tumour necrosis factor alpha therapy in inflammatory bowel disease World J Gastroenterol 21 2015 4773 4778
M.E. van der Valk, M.J. Mangen, M. Leenders, and et al. Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFalpha therapy: results from the COIN study Gut 63 2014 72 79
N. Khan, A.M. Abbas, G.R. Lichtenstein, and et al. Risk of lymphoma in patients with ulcerative colitis treated with thiopurines: a nationwide retrospective cohort study Gastroenterology 145 2013 1007 1015.e3
L. Beaugerie, N. Brousse, A.M. Bouvier, and et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study Lancet 374 2009 1617 1625
J. Kirchgesner, F. Carrat, J. Cosnes, and et al. Withdrawing or continuing maintenance treatment with thiopurines in patients with Crohn's disease in sustained clinical remission: a lifetime risk-benefit analysis (abstr) Gastroenterology 148 suppl 1 2015 S-231
J.S. Smolen, P. Emery, R. Fleischmann, and et al. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial Lancet 383 2014 321 332
M.L. Annunziata, L.G. Papparella, I. Sansoni, and et al. Normalized wall thickness at MRE predicts clinical remission in crohn's disease after infliximab discontinuation: a 5 years' follow-up study Gastroenterology 146 suppl 1 2014 S-246
K. Papamichael, K. Claes, M. de Bruyn, and et al. Serology panel for prediction relapse after discontinuation of infliximab in patients with Crohn's disease achieving clinical remission J Crohns Colitis 9 suppl 1 2015 S295 S296
