Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn’s Disease

Abstract Background & Aims Crohn’s disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. Methods We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. Results The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. Conclusions Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

[1]  Inge Christoffer Olsen,et al.  Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial , 2017, The Lancet.

[2]  M. Cottone,et al.  Tolerability profile of thiopurines in inflammatory bowel disease: a prospective experience , 2017, Scandinavian journal of gastroenterology.

[3]  M. Ingham,et al.  Predicting Pre-emptive Discussions of Biologic Treatment: Results from an Openness and Preference Survey of Inflammatory Bowel Disease Patients and Their Prescribers , 2017, Advances in Therapy.

[4]  N. Borruel,et al.  Patient preferences for inflammatory bowel disease treatment objectives. , 2017, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[5]  S. Eichner,et al.  Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in patients with Crohn's disease or ulcerative colitis who had failed conventional therapy , 2016, Alimentary pharmacology & therapeutics.

[6]  M. Silverberg,et al.  Development of the Harvey-Bradshaw Index-pro (HBI-PRO) Score to Assess Endoscopic Disease Activity in Crohn’s Disease , 2016, Journal of Crohn's & colitis.

[7]  A. Kaser,et al.  Long-term Efficacy of Vedolizumab for Crohn’s Disease , 2016, Journal of Crohn's & colitis.

[8]  M. Cvancarova,et al.  Switching from Remicade® to Remsima® is well Tolerated and Feasible: A Prospective, Open-label Study , 2016, Journal of Crohn's & colitis.

[9]  G. D'Haens,et al.  Histologic scoring indices for evaluation of disease activity in Crohn's disease. , 2016, The Cochrane database of systematic reviews.

[10]  P. Rutgeerts,et al.  The safety of vedolizumab for ulcerative colitis and Crohn's disease , 2016, Gut.

[11]  L. Peyrin-Biroulet,et al.  Patient Perspectives on Biosimilars: A Survey by the European Federation of Crohn’s and Ulcerative Colitis Associations , 2017, Journal of Crohn's & colitis.

[12]  H. Tilg,et al.  3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 1 Diagnosis and Medical Management , 2017, Journal of Crohn's & colitis.

[13]  B. Sands,et al.  Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease in Patients Naïve to or Who Have Failed Tumor Necrosis Factor Antagonist Therapy , 2017, Inflammatory bowel diseases.

[14]  J. Panés,et al.  Advances in Use of Endoscopy, Radiology, and Biomarkers to Monitor Inflammatory Bowel Diseases. , 2017, Gastroenterology.

[15]  D. Hommes,et al.  Value redefined for inflammatory bowel disease patients: a choice-based conjoint analysis of patients’ preferences , 2017, Quality of Life Research.

[16]  R. Khanna,et al.  Anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease. , 2016, The Cochrane database of systematic reviews.

[17]  Xiaojun Chen,et al.  Serum Albumin and C-Reactive Protein/Albumin Ratio Are Useful Biomarkers of Crohn's Disease Activity. , 2016, Medical science monitor : international medical journal of experimental and clinical research.

[18]  T. Matsui,et al.  Adalimumab Monotherapy and a Combination with Azathioprine for Crohn's Disease: A Prospective, Randomized Trial. , 2016, Journal of Crohn's & colitis.

[19]  G. Rogler,et al.  Experts Opinion on the Practical Use of Azathioprine and 6-Mercaptopurine in Inflammatory Bowel Disease , 2016, Inflammatory bowel diseases.

[20]  S. Ng,et al.  Development of an index to define overall disease severity in IBD , 2016, Gut.

[21]  P. Bampton,et al.  High Vitamin D–Binding Protein Concentration, Low Albumin, and Mode of Remission Predict Relapse in Crohn's Disease , 2016, Inflammatory bowel diseases.

[22]  S. Travis,et al.  Current best practice for disease activity assessment in IBD , 2016, Nature Reviews Gastroenterology &Hepatology.

[23]  Siddharth Singh,et al.  Comparative Effectiveness and Safety of Anti-Tumor Necrosis Factor Agents in Biologic-Naive Patients With Crohn's Disease. , 2016, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[24]  John T. Chang,et al.  The Real-World Effectiveness and Safety of Vedolizumab for Moderate–Severe Crohn’s Disease: Results From the US VICTORY Consortium , 2016, The American Journal of Gastroenterology.

[25]  C. Parker,et al.  Anti-tuberculous therapy for maintenance of remission in Crohn's disease. , 2016, The Cochrane database of systematic reviews.

[26]  J. Gisbert,et al.  Ustekinumab for the Treatment of Refractory Crohn's Disease: The Spanish Experience in a Large Multicentre Open-label Cohort , 2016, Inflammatory bowel diseases.

[27]  J. Fletcher,et al.  Radiological Response Is Associated With Better Long-Term Outcomes and Is a Potential Treatment Target in Patients With Small Bowel Crohn's Disease , 2016, The American Journal of Gastroenterology.

[28]  R. Hunt,et al.  The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults. , 2016, Gastroenterology.

[29]  P. Rutgeerts,et al.  Mo1880 Mucosal Healing and Dysplasia Surveillance in a Large Referral Center Cohort of Patients With Crohn's Disease and Ulcerative Colitis Treated With Vedolizumab , 2016 .

[30]  P. Wohl,et al.  Clinical monitoring: infliximab biosimilar CT-P13 in the treatment of Crohn’s disease and ulcerative colitis , 2016, Scandinavian journal of gastroenterology.

[31]  R. Laughlin,et al.  P-006 Evidence of Mucosal Healing in Patients with Crohn's Disease Treated with Open-Label Vedolizumab: A Case Series , 2016 .

[32]  S. Vermeire,et al.  Defining Disease Severity in Inflammatory Bowel Diseases: Current and Future Directions. , 2016, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[33]  A. Bitton,et al.  The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy. , 2016, Gastroenterology.

[34]  A. Akobeng,et al.  Glutamine for induction of remission in Crohn's disease. , 2016, The Cochrane database of systematic reviews.

[35]  N. Narula,et al.  Systematic review with meta‐analysis: mucosal healing is associated with improved long‐term outcomes in Crohn's disease , 2016, Alimentary pharmacology & therapeutics.

[36]  Dawn B. Beaulieu,et al.  Patients with Refractory Crohn's Disease Successfully Treated with Ustekinumab , 2016, Inflammatory bowel diseases.

[37]  A. Bitton,et al.  Mortality Trends in Crohn's Disease and Ulcerative Colitis: A Population-based Study in Québec, Canada , 2016, Inflammatory bowel diseases.

[38]  A. Amiot,et al.  Subcutaneous Ustekinumab Provides Clinical Benefit for Two-Thirds of Patients With Crohn's Disease Refractory to Anti-Tumor Necrosis Factor Agents. , 2016, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[39]  K. Farkas,et al.  Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort. , 2016, Journal of Crohn's & colitis.

[40]  G. D'Haens,et al.  Endoscopic scoring indices for evaluation of disease activity in Crohn's disease. , 2016, The Cochrane database of systematic reviews.

[41]  P. Rutgeerts,et al.  Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. , 2016, The New England journal of medicine.

[42]  F. Johnson,et al.  Inflammatory Bowel Disease Patients’ Willingness to Accept Medication Risk to Avoid Future Disease Relapse , 2015, The American Journal of Gastroenterology.

[43]  J. Jahnsen,et al.  Biosimilar infliximab (CT-P13) in the treatment of inflammatory bowel disease: A Norwegian observational study , 2015, Expert review of gastroenterology & hepatology.

[44]  S. Vermeire,et al.  IOIBD technical review on endoscopic indices for Crohn's disease clinical trials , 2015, Gut.

[45]  T. Murdoch,et al.  Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target , 2015, The American Journal of Gastroenterology.

[46]  Z. Dzierżewicz,et al.  THE EFFECT OF SULFASALAZINE AND 5-AMINOSALICYLIC ACID ON THE SECRETION OF INTERLEUKIN 8 BY HUMAN COLON MYOFIBROBLASTS. , 2015, Acta poloniae pharmaceutica.

[47]  J. Gisbert,et al.  Systematic review: factors associated with relapse of inflammatory bowel disease after discontinuation of anti‐TNF therapy , 2015, Alimentary pharmacology & therapeutics.

[48]  P. Lakatos,et al.  Prevalence and predictors of hospitalization in Crohn's disease in a prospective population-based inception cohort from 2000-2012. , 2015, World journal of gastroenterology.

[49]  J. Stoker,et al.  Grading of Crohn’s disease activity using CT, MRI, US and scintigraphy: a meta-analysis , 2015, European Radiology.

[50]  S. Hanauer,et al.  Treat to target: a proposed new paradigm for the management of Crohn's disease. , 2015, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[51]  S. Bonovas,et al.  Systematic review with network meta‐analysis: comparative efficacy and safety of budesonide and mesalazine (mesalamine) for Crohn's disease , 2015, Alimentary pharmacology & therapeutics.

[52]  W. Sandborn,et al.  Population pharmacokinetics‐pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease , 2015, Alimentary pharmacology & therapeutics.

[53]  G. Guyatt,et al.  Guideline panels should not GRADE good practice statements. , 2015, Journal of clinical epidemiology.

[54]  A. Bitton,et al.  Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus. , 2015, Gastroenterology.

[55]  J. Gisbert,et al.  Systematic review with meta‐analysis: the efficacy of a second anti‐TNF in patients with inflammatory bowel disease whose previous anti‐TNF treatment has failed , 2015, Alimentary pharmacology & therapeutics.

[56]  S. McClave,et al.  Specialized enteral nutrition therapy in Crohn’s disease patients on maintenance infliximab therapy: a meta-analysis , 2015, Therapeutic advances in gastroenterology.

[57]  Jingjing Ma,et al.  Use of antibiotics in patients with Crohn's disease: A systematic review and meta‐analysis , 2015, Journal of digestive diseases.

[58]  G. Kaplan,et al.  Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: a network meta-analysis. , 2015, Gastroenterology.

[59]  J. Fletcher,et al.  CT and MR enterography in Crohn’s disease: current and future applications , 2015, Abdominal Imaging.

[60]  M. Vandervoort,et al.  A retrospective analysis: the development of patient reported outcome measures for the assessment of Crohn's disease activity , 2015, Alimentary pharmacology & therapeutics.

[61]  M. Murad,et al.  Efficacy and Safety of Natalizumab and Vedolizumab for the Management of Crohn's Disease: A Systematic Review and Meta-analysis , 2014, Inflammatory bowel diseases.

[62]  B. Sands,et al.  Converging goals of treatment of inflammatory bowel disease from clinical trials and practice. , 2015, Gastroenterology.

[63]  W. Petritsch,et al.  Withdrawal of Long-Term Maintenance Treatment with Azathioprine Tends to Increase Relapse Risk in Patients with Crohn’s Disease , 2015, Digestive Diseases and Sciences.

[64]  S. Langham,et al.  The Economic and Quality-of-Life Burden of Crohn’s Disease in Europe and the United States, 2000 to 2013: A Systematic Review , 2015, Digestive Diseases and Sciences.

[65]  David M Richards,et al.  Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease , 2014, Clinical and experimental gastroenterology.

[66]  A. Bitton,et al.  Adalimumab monotherapy versus combination therapy with immunomodulators in patients with Crohn's disease: a systematic review and meta-analysis. , 2014, Journal of Crohn's & colitis.

[67]  Zhen Wang,et al.  Comparative efficacy of biologic therapy in biologic-naïve patients with Crohn disease: a systematic review and network meta-analysis. , 2014, Mayo Clinic proceedings.

[68]  Shuyi Li,et al.  Evaluation of "top-down" treatment of early Crohn's disease by double balloon enteroscopy. , 2014, World journal of gastroenterology.

[69]  G. Greenberg,et al.  The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease , 2014, Gut.

[70]  J. Xu,et al.  Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed. , 2014, Gastroenterology.

[71]  L. Kupčinskas,et al.  Once versus three times daily dosing of oral budesonide for active Crohn's disease: a double-blind, double-dummy, randomised trial. , 2014, Journal of Crohn's & colitis.

[72]  F. Carrat,et al.  Increased risk of acute myeloid leukemias and myelodysplastic syndromes in patients who received thiopurine treatment for inflammatory bowel disease. , 2014, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[73]  C. Bernstein,et al.  Canadian Association of Gastroenterology position statement regarding the use of thiopurines for the treatment of inflammatory bowel disease. , 2014, Canadian journal of gastroenterology & hepatology.

[74]  G. Kaplan,et al.  Cannabis Use Provides Symptom Relief in Patients with Inflammatory Bowel Disease but Is Associated with Worse Disease Prognosis in Patients with Crohn's Disease , 2014, Inflammatory bowel diseases.

[75]  A. Cohen,et al.  Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn's disease. , 2014, Gastroenterology.

[76]  A. Griffiths,et al.  Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology. , 2014, Gastroenterology.

[77]  A. Griffiths,et al.  Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease. , 2014, The Cochrane database of systematic reviews.

[78]  J. Macdonald,et al.  Low dose naltrexone for induction of remission in Crohn's disease. , 2014, The Cochrane database of systematic reviews.

[79]  M. Vandervoort,et al.  P176 Patient reported outcome measures derived from the Crohn's Disease Activity Index: Correlation between PRO2 and PRO3 scores and CDAI-defined clinical thresholds , 2014 .

[80]  Huyuan Yang,et al.  DOP058 Pharmacokinetic and pharmacodynamic relationship and immunogenicity of vedolizumab in adults with inflammatory bowel disease: Additional results from the GEMINI 1 and 2 studies , 2014 .

[81]  J. Ariyaratnam,et al.  Association Between Thiopurine Use and Nonmelanoma Skin Cancers in Patients With Inflammatory Bowel Disease: A Meta-Analysis , 2014, The American Journal of Gastroenterology.

[82]  S. Saxena,et al.  The Role of Thiopurines in Reducing the Need for Surgical Resection in Crohn's Disease: A Systematic Review and Meta-Analysis , 2014, The American Journal of Gastroenterology.

[83]  Y. Kohgo,et al.  Probiotic treatments for induction and maintenance of remission in inflammatory bowel diseases: a meta-analysis of randomized controlled trials , 2014, Clinical Journal of Gastroenterology.

[84]  Y. Falck‐Ytter,et al.  AGA American Gastroenterological Association Institute Guideline on the Use of Thiopurines , Methotrexate , and Anti – TNF-a Biologic Drugs for the Induction and Maintenance of Remission in In fl ammatory Crohn ’ s Disease , 2022 .

[85]  E. Louis,et al.  Role of endoscopy, cross-sectional imaging and biomarkers in Crohn's disease monitoring , 2013, Gut.

[86]  F. Carrat,et al.  Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer , 2013, Gut.

[87]  M. Sans,et al.  Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn's disease. , 2013, Gastroenterology.

[88]  J. Mary,et al.  Early administration of azathioprine vs conventional management of Crohn's Disease: a randomized controlled trial. , 2013, Gastroenterology.

[89]  I. Dotan,et al.  Cannabis induces a clinical response in patients with Crohn's disease: a prospective placebo-controlled study. , 2013, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[90]  Kristin Stephens,et al.  Vedolizumab as induction and maintenance therapy for Crohn's disease. , 2013, The New England journal of medicine.

[91]  L. A. Christensen,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 , 2013, Gut.

[92]  E. Louis,et al.  Evolving Definitions of Remission in Crohn’s Disease , 2013, Inflammatory bowel diseases.

[93]  Y. Falck‐Ytter,et al.  The AGA institute process for developing clinical practice guidelines part one: grading the evidence. , 2013, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[94]  T. Hibi,et al.  Efficacy and tolerability of oral budesonide in Japanese patients with active Crohn's disease: a multicentre, double-blind, randomized, parallel-group Phase II study. , 2013, Journal of Crohn's & colitis.

[95]  D. Hommes,et al.  Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI) , 2013, Gut.

[96]  R. Kim,et al.  Pharmacokinetic profiles for oral and subcutaneous methotrexate in patients with Crohn's disease , 2013, Alimentary pharmacology & therapeutics.

[97]  A. Cheifetz,et al.  Impact of Antibodies to Infliximab on Clinical Outcomes and Serum Infliximab Levels in Patients With Inflammatory Bowel Disease (IBD): A Meta-Analysis , 2013, The American Journal of Gastroenterology.

[98]  T. Dassopoulos,et al.  American Gastroenterological Association Institute technical review on the use of thiopurines, methotrexate, and anti-TNF-α biologic drugs for the induction and maintenance of remission in inflammatory Crohn's disease. , 2013, Gastroenterology.

[99]  J. Macdonald,et al.  Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease. , 2013, The Cochrane database of systematic reviews.

[100]  G. Greenberg,et al.  Ustekinumab induction and maintenance therapy in refractory Crohn's disease. , 2012, The New England journal of medicine.

[101]  Ren Mao,et al.  Fecal calprotectin in predicting relapse of inflammatory bowel diseases: A meta‐analysis of prospective studies , 2012, Inflammatory bowel diseases.

[102]  Steve Halligan,et al.  Non-perforating small bowel Crohn's disease assessed by MRI enterography: derivation and histopathological validation of an MR-based activity index. , 2012, European journal of radiology.

[103]  M. Papp,et al.  High‐sensitivity C‐reactive protein for identification of disease phenotype, active disease, and clinical relapses in Crohn's disease: A marker for patient classification? , 2012, Inflammatory bowel diseases.

[104]  W. Sandborn,et al.  Serious Infection and Mortality in Patients With Crohn's Disease: More Than 5 Years of Follow-Up in the TREAT™ Registry , 2012, The American Journal of Gastroenterology.

[105]  H. Sokol,et al.  Clinical, serological and genetic predictors of inflammatory bowel disease course. , 2012, World journal of gastroenterology.

[106]  K. Lomax,et al.  Patient perspectives on the impact of Crohn’s disease: results from group interviews , 2012, Patient preference and adherence.

[107]  E. Cabré,et al.  Omega-3 fatty acids and inflammatory bowel diseases – a systematic review , 2012, British Journal of Nutrition.

[108]  P. Rutgeerts,et al.  Adalimumab induces and maintains mucosal healing in patients with Crohn's disease: data from the EXTEND trial. , 2012, Gastroenterology.

[109]  M. Kersten,et al.  Long-term follow-up of autologous hematopoietic stem cell transplantation for severe refractory Crohn's disease. , 2011, Journal of Crohn's & colitis.

[110]  P. Rutgeerts,et al.  Switch to adalimumab in patients with Crohn's disease controlled by maintenance infliximab: prospective randomised SWITCH trial , 2011, Gut.

[111]  P. Moayyedi,et al.  Antibiotic Therapy in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis , 2011, The American Journal of Gastroenterology.

[112]  L. Peyrin-Biroulet,et al.  Loss of Response and Need for Adalimumab Dose Intensification in Crohn's Disease: A Systematic Review , 2011, The American Journal of Gastroenterology.

[113]  P. Moayyedi,et al.  Efficacy of Immunosuppressive Therapy for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis , 2011, The American Journal of Gastroenterology.

[114]  P. Moayyedi,et al.  Efficacy of Biological Therapies in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis , 2011, The American Journal of Gastroenterology.

[115]  P. Moayyedi,et al.  Glucocorticosteroid Therapy in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis , 2011, The American Journal of Gastroenterology.

[116]  P. Moayyedi,et al.  Efficacy of 5-Aminosalicylates in Crohn's Disease: Systematic Review and Meta-Analysis , 2011, The American Journal of Gastroenterology.

[117]  D. Porter,et al.  A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. , 2011, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[118]  J. Sanderson,et al.  Review article: malignancy on thiopurine treatment with special reference to inflammatory bowel disease , 2010, Alimentary pharmacology & therapeutics.

[119]  P. Rutgeerts,et al.  Infliximab, azathioprine, or combination therapy for Crohn's disease. , 2010, The New England journal of medicine.

[120]  Stefan Schreiber,et al.  Correlation between the Crohn's disease activity and Harvey-Bradshaw indices in assessing Crohn's disease severity. , 2010, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[121]  C. O'Morain,et al.  The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Current management. , 2010, Journal of Crohn's & colitis.

[122]  P. Rutgeerts,et al.  Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. , 2010, Gastroenterology.

[123]  S. Hanauer,et al.  Aminosalicylates for induction of remission or response in Crohn's disease. , 2010, The Cochrane database of systematic reviews.

[124]  F. Carrat,et al.  Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study , 2009, The Lancet.

[125]  P. Rutgeerts,et al.  Mucosal healing predicts long‐term outcome of maintenance therapy with infliximab in Crohn's disease , 2009, Inflammatory bowel diseases.

[126]  L. Guidi,et al.  Enteroclysis CT and PEG-CT in patients with previous small-bowel surgical resection for Crohn’s disease: CT findings and correlation with endoscopy , 2009, European Radiology.

[127]  P. Rutgeerts,et al.  Oral budesonide for maintenance of remission of Crohn’s disease: a pooled safety analysis , 2009, Alimentary pharmacology & therapeutics.

[128]  J. Gisbert,et al.  Loss of Response and Requirement of Infliximab Dose Intensification in Crohn's Disease: A Review , 2009, The American Journal of Gastroenterology.

[129]  I. Ordás,et al.  Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn’s disease , 2009, Gut.

[130]  E. Benchimol,et al.  Budesonide for maintenance of remission in Crohn's disease. , 2009, The Cochrane database of systematic reviews.

[131]  M. Cepoiu,et al.  Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn's disease. , 2009, The Cochrane database of systematic reviews.

[132]  J. Macdonald,et al.  Methotrexate for maintenance of remission in Crohn's disease. , 2009, The Cochrane database of systematic reviews.

[133]  A. Griffiths,et al.  Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease. , 2009, The Cochrane database of systematic reviews.

[134]  A. Cohen,et al.  Treatment of active Crohn's disease with MLN0002, a humanized antibody to the alpha4beta7 integrin. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[135]  A. Zinsmeister,et al.  Relationships between disease activity and serum and fecal biomarkers in patients with Crohn's disease. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[136]  P. Rutgeerts,et al.  A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease. , 2008, Gastroenterology.

[137]  A. Akobeng,et al.  Probiotics for induction of remission in Crohn's disease. , 2008, The Cochrane database of systematic reviews.

[138]  G. Guyatt,et al.  Going from evidence to recommendations , 2008, BMJ : British Medical Journal.

[139]  G. Guyatt,et al.  GRADE: an emerging consensus on rating quality of evidence and strength of recommendations , 2008, BMJ : British Medical Journal.

[140]  A. Griffiths,et al.  Traditional corticosteroids for induction of remission in Crohn's disease. , 2008, The Cochrane database of systematic reviews.

[141]  M. Vos,et al.  Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial , 2008, The Lancet.

[142]  S. Bickston,et al.  Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn's disease. , 2008, The Cochrane database of systematic reviews.

[143]  J. Belaiche,et al.  Predictors of severe Crohn's disease , 2008, Scandinavian journal of gastroenterology.

[144]  M. Färkkilä,et al.  Crohn's disease activity assessed by fecal calprotectin and lactoferrin: Correlation with Crohn's disease activity index and endoscopic findings , 2008, Inflammatory bowel diseases.

[145]  A. Griffiths,et al.  Budesonide for induction of remission in Crohn's disease. , 2008, The Cochrane database of systematic reviews.

[146]  S. Nikfar,et al.  A Meta-Analysis on the Efficacy of Probiotics for Maintenance of Remission and Prevention of Clinical and Endoscopic Relapse in Crohn’s Disease , 2008, Digestive Diseases and Sciences.

[147]  A. Akobeng,et al.  Enteral nutrition for maintenance of remission in Crohn's disease. , 2007, The Cochrane database of systematic reviews.

[148]  S. Hanauer,et al.  Adalimumab Induction Therapy for Crohn Disease Previously Treated with Infliximab , 2007, Annals of Internal Medicine.

[149]  P. Rutgeerts,et al.  Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. , 2007, Gastroenterology.

[150]  A. Tursi,et al.  Beclomethasone dipropionate for the treatment of mild-to-moderate Crohn's disease: an open-label, budesonide-controlled, randomized study. , 2006, Medical science monitor : international medical journal of experimental and clinical research.

[151]  J. Mary,et al.  Infliximab plus azathioprine for steroid-dependent Crohn's disease patients: a randomized placebo-controlled trial. , 2006, Gastroenterology.

[152]  M. Bala,et al.  Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease , 2006 .

[153]  P. Seksik,et al.  Predictors of Crohn's disease. , 2006, Gastroenterology.

[154]  W. Tremaine,et al.  American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. , 2006, Gastroenterology.

[155]  P. Rutgeerts,et al.  Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. , 2006, Gastroenterology.

[156]  X. Thuru,et al.  Mu opioid receptor expression is increased in inflammatory bowel diseases: implications for homeostatic intestinal inflammation , 2005, Gut.

[157]  J. Satsangi,et al.  Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. , 2005, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[158]  D. Felsenberg,et al.  Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn's disease. , 2005, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[159]  B. Feagan,et al.  Methotrexate for induction of remission in refractory Crohn's disease. , 2005, The Cochrane database of systematic reviews.

[160]  A. Griffiths,et al.  Corticosteroids for maintenance of remission in Crohn's disease. , 2003, The Cochrane database of systematic reviews.

[161]  H. Halkin,et al.  Bioavailability of oral vs. subcutaneous low‐dose methotrexate in patients with Crohn's disease , 2003, Alimentary pharmacology & therapeutics.

[162]  G. Lichtenstein,et al.  Corticosteroids in Crohn’s disease , 2002, American Journal of Gastroenterology.

[163]  R. Jian,et al.  Long term outcome of patients with active Crohn's disease exhibiting extensive and deep ulcerations at colonoscopy , 2002, American Journal of Gastroenterology.

[164]  A. Zinsmeister,et al.  Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. , 2001, Gastroenterology.

[165]  H. Ogata,et al.  Measurement of Colonic Mucosal Concentrations of 5-Aminosalicylic Acid Is Useful for Estimating Its Therapeutic Efficacy in Distal Ulcerative Colitis: Comparison of Orally Administered Mesalamine and Sulfasalazine , 2001, Inflammatory bowel diseases.

[166]  G. Greenberg,et al.  A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease , 2000 .

[167]  M. Suarez‐Almazor,et al.  Calcium and vitamin D for corticosteroid-induced osteoporosis. , 1998, The Cochrane database of systematic reviews.

[168]  G. D'Haens,et al.  Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: A European multicenter trial. , 1999, Gastroenterology.

[169]  B. Korelitz,et al.  Intravenous Corticotrophin vs. Hydrocortisone in the Treatment of Hospitalized Patients with Crohn's Disease: A Randomized Double-Blind Study and Follow-Up , 1998 .

[170]  A. Lavy,et al.  Methotrexate in chronic active Crohn's disease: a double-blind, randomized, Israeli multicenter trial. , 1997, The American journal of gastroenterology.

[171]  S. Targan,et al.  A Short-Term Study of Chimeric Monoclonal Antibody cA2 to Tumor Necrosis Factor α for Crohn's Disease , 1997 .

[172]  D. Cook,et al.  The Relation between Systematic Reviews and Practice Guidelines , 1997, Annals of Internal Medicine.

[173]  J. Schölmerich,et al.  Oral pH-modified release budesonide versus 6-methylprednisolone in active Crohn's disease. German/Austrian Budesonide Study Group. , 1996, European journal of gastroenterology & hepatology.

[174]  Loyd,et al.  Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. , 1995, The New England journal of medicine.

[175]  P. Munkholm,et al.  Frequency of glucocorticoid resistance and dependency in Crohn's disease. , 1994, Gut.

[176]  J. Belaiche,et al.  Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn's disease. A prospective multicentre study of 121 cases. The Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives. , 1994, Gut.

[177]  R. Modigliani,et al.  Clinical, biological, and endoscopic picture of attacks of Crohn's disease. Evolution on prednisolone. Groupe d'Etude Thérapeutique des Affections Inflammatoires Digestives. , 1990, Gastroenterology.

[178]  D. Jewell,et al.  Use of an intravenous steroid regimen in the treatment of acute Crohn's disease. , 1986, Journal of clinical gastroenterology.

[179]  K. Ewe,et al.  European cooperative Crohn's disease study (ECCDS) : Results of drug treatment , 1984 .

[180]  G. T. ten Velde,et al.  Effect of sulphasalazine in patients with active Crohn's disease: a controlled double-blind study. , 1981, Gut.

[181]  R. Weinshilboum,et al.  Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. , 1980, American journal of human genetics.

[182]  R. F. Harvey,et al.  A SIMPLE INDEX OF CROHN'S-DISEASE ACTIVITY , 1980, The Lancet.

[183]  R. Summers,et al.  National Cooperative Crohn's Disease Study: results of drug treatment. , 1979, Gastroenterology.

[184]  F Kern,et al.  Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. , 1976, Gastroenterology.

[185]  Norman Crolee Dalkey,et al.  An experimental study of group opinion , 1969 .