How will evolving future therapies and strategies change how we position the use of biologics in moderate to severely active inflammatory bowel disease

Inflammatory Bowel Diseases

Volumn 22, Issue 4, 2016, Pages 998-1009

  Dulai, Parambir S ^a,b   Singh, Siddharth ^a   Casteele, Niels V ^a,b,c   Boland, Brigid S ^a   Sandborn, William J ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b ROBARTS RESEARCH INSTITUTE   (Canada)

^c UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

biologics; biosimilars; comparative effectiveness; small molecules

Indexed keywords

BIOLOGICAL PRODUCT; MONGERSEN; OZANIMOD; TOFACITINIB; USTEKINUMAB; VEDOLIZUMAB;

BIOLOGICAL ACTIVITY; COMPARATIVE EFFECTIVENESS; CROHN DISEASE; DRUG MECHANISM; HEALING; HEALTH CARE PRACTICE; HOSPITALIZATION; HUMAN; INFLAMMATORY BOWEL DISEASE; MAINTENANCE THERAPY; PRIORITY JOURNAL; REMISSION; REVIEW; TREATMENT OUTCOME; ULCERATIVE COLITIS; INFLAMMATORY BOWEL DISEASES; SEVERITY OF ILLNESS INDEX;

BIOLOGICAL PRODUCTS; HUMANS; INFLAMMATORY BOWEL DISEASES; SEVERITY OF ILLNESS INDEX;

EID: 84962214384     PISSN: 10780998     EISSN: 15364844     Source Type: Journal    
DOI: 10.1097/MIB.0000000000000661     Document Type: Review

References (119)

1. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009; 361:2066-2078.
2. Ordas I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet. 2012; 380:1606-1619.
3. Baumgart DC, Sandborn WJ. Crohn?s disease. Lancet. 2012;380: 1590-1605.
4. Williet N, Sandborn WJ, Peyrin-Biroulet L. Patient-reported outcomes as primary end points in clinical trials of inflammatory bowel disease. Clin Gastroenterol Hepatol. 2014;12:1246-1256.e6.
5. Peyrin-Biroulet L, Reinisch W, Colombel JF, et al. Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn?s disease in the SONIC trial. Gut. 2014;63:88-95.
6. Levesque BG, Sandborn WJ, Ruel J, et al. Converging Goals of treatment for inflammatory bowel disease, from clinical trials and practice. Gastroenterology. 2015;148:37-51.
7. Dhaens G, Sandborn WJ, Feagan BG, et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007;132:763-786.
8. Dhaens GR, Fedorak R, Lemann M, et al. Endpoints for clinical trials evaluating disease modification and structural damage in adults with Crohn?s disease. Inflamm Bowel Dis. 2009;15:1599-1604.
9. Dhaens 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.
10. Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn?s disease. N Engl J Med. 2010;362: 1383-1395.
11. Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014;146:392-400.e3.
12. Dulai PS, Siegel CA, Colombel JF, et al. Systematic review: monotherapy with antitumour necrosis factor alpha agents versus combination therapy with an immunosuppressive for IBD. Gut. 2014;63:1843-1853.
13. Khanna R, Levesque BG, Bressler B, et al. 1053 early combined immunosuppression for the management of Crohn?s disease: a communitybased Cluster randomized trial. Gastroenterology. 2015;146:S-187.
14. Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148:1320-1329 e3.
15. Dulai PS, Levesque BG, Feagan BG, et al. Assessment of mucosal healing in inflammatory bowel disease: review. Gastrointest Endosc. 2015;82:246-255.
16. Gunnarsson C, Chen J, Rizzo JA, et al. Direct health care insurer and out-of-pocket expenditures of inflammatory bowel disease: evidence from a US national survey. Dig Dis Sci. 2012;57:3080-3091.
17. Kappelman MD, Rifas-Shiman SL, Kleinman K, et al. The prevalence and geographic distribution of Crohn?s disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol. 2007;5:1424-1429.
18. van der Valk ME, Mangen MJ, Leenders M, et al. Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNF alpha therapy: results from the COIN study. Gut. 2014;63:72-79.
19. Cipriani A, Higgins JP, Geddes JR, et al. Conceptual and technical challenges in network meta-Analysis. Ann Intern Med. 2013;159:130-137.
20. Bonovas S, Moja L, Danese S. In the presence of Conceptual heterogeneity, results of network meta-Analysis comparing therapies in Crohn?s disease need to be interpreted with caution. Gastroenterology. 2015;148: 1483-1484.
21. 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.
22. Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-Tumor necrosis factor monoclonal antibody (adalimumab) in Crohn?s disease: the CLASSIC-I trial. Gastroenterology. 2006;130:323-333; quiz 591.
23. Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn?s disease. N Engl J Med. 2007;357:228-238.
24. Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn?s disease. N Engl J Med. 2013;369: 711-721.
25. Ford AC, Sandborn WJ, Khan KJ, et al. Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-Analysis. Am J Gastroenterol. 2011;106:644-659; quiz 660.
26. Stidham RW, Lee TC, Higgins PD, et al. Systematic review with network meta-Analysis: the efficacy of anti-TNF agents for the treatment of Crohn?s disease. Aliment Pharmacol Ther. 2014;39:1349-1362.
27. Singh S, Garg SK, Pardi DS, et al. Comparative efficacy of biologic therapy in biologic-naive patients with Crohn disease: a systematic review and network meta-Analysis. Mayo Clin Proc. 2014;89: 1621-1635.
28. Hazlewood GS, Rezaie A, Borman M, et al. Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn?s disease: a network meta-Analysis. Gastroenterology. 2015;148:344-354.e5; quiz e14-5.
29. Sands BE, Feagan BG, Rutgeerts P, et al. Effects of vedolizumab induction therapy for patients with Crohn?s disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology. 2014;147:618-627.e3.
30. Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn?s disease: the CHARM trial. Gastroenterology. 2007;132:52-65.
31. Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn?s disease. N Engl J Med. 2007; 357:239-250.
32. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn?s disease: the ACCENT I randomised trial. Lancet. 2002;359: 1541-1549.
33. Rutgeerts P, Van Assche G, Sandborn WJ, et al. Adalimumab induces and maintains mucosal healing in patients with Crohn?s disease: data from the EXTEND trial. Gastroenterology. 2012;142:1102-1111.e2.
34. Hebuterne X, Lemann M, Bouhnik Y, et al. Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn?s disease following treatment with certolizumab pegol. Gut. 2013;62: 201-208.
35. Rutgeerts P, Feagan BG, Lichtenstein GR, et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn?s disease. Gastroenterology. 2004;126:402-413.
36. Lichtenstein GR, Yan S, Bala M, et al. Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn?s disease. Gastroenterology. 2005;128:862-869.
37. Costa J, Magro F, Caldeira D, et al. Infliximab reduces hospitalizations and surgery interventions in patients with inflammatory bowel disease: a systematic review and meta-Analysis. Inflamm Bowel Dis. 2013;19: 2098-2110.
38. Taxonera C, Rodrigo L, Casellas F, et al. Infliximab maintenance therapy is associated with decreases in direct resource use in patients with luminal or fistulizing Crohn?s disease. J Clin Gastroenterol. 2009;43:950-956.
39. Singh S, Pardi DS. Update on anti-Tumor necrosis factor agents in Crohn disease. Gastroenterol Clin North Am. 2014;43:457-478.
40. Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699-710.
41. Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-To-severe ulcerative colitis. Gastroenterology. 2012;142:257-265.e1-3.
42. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353: 2462-2476.
43. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-To-severe ulcerative colitis. Gastroenterology. 2014;146:96-109.e1.
44. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-Tosevere ulcerative colitis. Gastroenterology. 2014;146:85-95; quiz e14-5.
45. Stidham RW, Lee TC, Higgins PD, et al. Systematic review with network meta-Analysis: the efficacy of anti-Tumour necrosis factor-Alpha agents for the treatment of ulcerative colitis. Aliment Pharmacol Ther. 2014;39:660-671.
46. Thorlund K, Druyts E, Mills EJ, et al. Adalimumab versus infliximab for the treatment of moderate to severe ulcerative colitis in adult patients naive to anti-TNF therapy: an indirect treatment comparison meta-Analysis. J Crohns Colitis. 2014;8:571-581.
47. Danese S, Fiorino G, Peyrin-Biroulet L, et al. Biological agents for moderately to severely active ulcerative colitis: a systematic review and network meta-Analysis. Ann Intern Med. 2014;160:704-711.
48. Sandborn WJ, Rutgeerts P, Feagan BG, et al. Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology. 2009;137:1250-1260; quiz 1520.
49. Feagan BG, Sandborn WJ, Lazar A, et al. Adalimumab therapy is associated with reduced risk of hospitalization in patients with ulcerative colitis. Gastroenterology. 2014;146:110-118.e3.
50. Lopez A, Ford AC, Colombel JF, et al. Efficacy of tumour necrosis factor antagonists on remission, colectomy and hospitalisations in ulcerative colitis: meta-Analysis of placebo-controlled trials. Dig Liver Dis. 2015;47:356-364.
51. Ha C, Ullman TA, Siegel CA, et al. Patients enrolled in randomized controlled trials do not represent the inflammatory bowel disease patient population. Clin Gastroenterol Hepatol. 2012;10:1002-1007; quiz e78.
52. Mould DR, Green B. Pharmacokinetics and pharmacodynamics of monoclonal antibodies: concepts and lessons for drug development. Bio-Drugs. 2010;24:23-39.
53. Roskos LK, Davis CG, Schwab GM. The clinical pharmacology of therapeutic monoclonal antibodies. Drug Dev Res. 2004;61:108-120.
54. Sharma S, Eckert D, Hyams JS, et al. Pharmacokinetics and exposureefficacy relationship of adalimumab in pediatric patients with moderate to severe Crohn?s disease: results from a randomized, multicenter, phase-3 study. Inflamm Bowel Dis. 2015;21:783-792.
55. Cornillie F, Hanauer SB, Diamond RH, et al. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial. Gut. 2014;63:1721-1727.
56. Colombel JF, Sandborn WJ, Allez M, et al. Association between plasma concentrations of certolizumab pegol and endoscopic outcomes of patients with Crohn?s disease. Clin Gastroenterol Hepatol. 2014;12: 423-431.e1.
57. Adedokun OJ, Sandborn WJ, Feagan BG, et al. Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. Gastroenterology. 2014;147:1296-1307 e5.
58. Mostafa NM, Eckert D, Pradhan RS, et al. P333 Exposure-Efficacy relationship (ER) for adalimumab during induction phase of treatment of adult patients with moderate to severe ulcerative colitis (UC). United Eur Gastroenterol J. 2013;1:A221-A222.
59. Loste MA, Casteele NV, Vermeire S, et al. A panel to predict long-Term outcome of infliximab therapy for patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2015;13:531-538.
60. Baert F, Drobne D, Gils A, et al. Early trough levels and antibodies to infliximab predict safety and Success of Reinitiation of infliximab therapy. Clin Gastroenterol Hepatol. 2014;12:1474-1481.
61. Singh N, Rosenthal CJ, Melmed GY, et al. Early infliximab trough levels are associated with persistent remission in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2014;20:1708-1713.
62. 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.
63. Paul S, Del Tedesco E, Marotte H, et al. Therapeutic drug monitoring of infliximab and mucosal healing in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis. 2013;19:2568-2576.
64. Levesque BG, Greenberg GR, Zou G, et al. A prospective cohort study to determine the relationship between serum infliximab concentration and efficacy in patients with luminal Crohn?s disease. Aliment Pharmacol Ther. 2014;39:1126-1135.
65. Vande Casteele N, Khanna R, Levesque BG, et al. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn?s disease. Gut. 2015;64:1539-1545.
66. Yarur AJ, Kubiliun MJ, Czul F, et al. Concentrations of 6-Thioguanine Nucleotide Correlate with trough levels of infliximab in patients with inflammatory bowel disease on combination therapy. Clin Gastroenterol Hepatol. 2015;13:1118-1124.
67. Drobne D, Bossuyt P, Breynaert C, et al. Withdrawal of Immunomodulators after co-Treatment does not reduce trough level of infliximab in patients with Crohn?s disease. Clin Gastroenterol Hepatol. 2015;13: 514-521.
68. Baert F, Vande Casteele N, Tops S, et al. Prior response to infliximab and early serum drug concentrations predict effects of adalimumab in ulcerative colitis. Aliment Pharmacol Ther. 2014;40:1324-1332.
69. Mazor Y, Almog R, Kopylov U, et al. Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn?s disease. Aliment Pharmacol Ther. 2014;40:620-628.
70. Roblin X, Marotte H, Rinaudo M, et al. Association between pharmacokinetics of adalimumab and mucosal healing in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2014;12:80-84 e2.
71. Adedokun OJ, Sandborn WJ, Feagan BG, et al. Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. Gastroenterology. 2014;147:1296-1307.
72. Feagan BG, McDonald JW, Panaccione R, et al. Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn?s disease. Gastroenterology. 2014;146:681-688.e1.
73. Steenholdt C, Brynskov J, Thomsen OO, et al. Individualised therapy is more cost-Effective than dose intensification in patients with Crohn?s disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut. 2014;63:919-927.
74. Steenholdt C, Brynskov J, Thomsen OO, et al. Individualized therapy is a long-Term cost-Effective method compared to dose intensification in Crohn?s disease patients failing infliximab. Dig Dis Sci. 2015.
75. Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148:1320-1329.
76. Sandborn WJ, Gasink C, Gao LL, et al. Ustekinumab induction and maintenance therapy in refractory Crohn?s disease. N Engl J Med. 2012;367:1519-1528.
77. Monteleone G, Kumberova A, Croft NM, et al. Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease. J Clin Invest. 2001;108:601-609.
78. Monteleone G, Neurath MF, Ardizzone S, et al. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn?s disease. N Engl J Med. 2015;372:1104-1113.
79. Sandborn WJ, Ghosh S, Panes J, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med. 2012;367:616-624.
80. Sandborn WJ, Ghosh S, Panes J, et al. A phase 2 study of tofacitinib, an oral Janus kinase inhibitor, in patients with Crohn?s disease. Clin Gastroenterol Hepatol. 2014;12:1485-1493.e2.
81. Sandborn W, Feagan BG, Wolf DC, et al. 445 the TOUCHSTONE study: a randomized, double-Blind, placebo-controlled induction trial of an oral S1P receptor modulator (RPC1063) in moderate to severe ulcerative colitis. Gastroenterology. 2015;148:S-93.
82. Beaugerie L, Seksik P, Nion-Larmurier I, et al. Predictors of Crohn?s disease. Gastroenterology. 2006;130:650-656.
83. Lazarev M, Huang C, Bitton A, et al. Relationship between proximal Crohn?s disease location and disease behavior and surgery: a crosssectional study of the IBD Genetics Consortium. Am J Gastroenterol. 2013;108:106-112.
84. Ramadas AV, Gunesh S, Thomas GA, et al. Natural history of Crohn?s disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates. Gut. 2010; 59:1200-1206.
85. Thia KT, Sandborn WJ, Harmsen WS, et al. Risk factors associated with progression to intestinal complications of Crohn?s disease in a population-based cohort. Gastroenterology. 2010;139:1147-1155.
86. Romberg-Camps MJ, Dagnelie PC, Kester AD, et al. Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease. Am J Gastroenterol. 2009;104:371-383.
87. Tarrant KM, Barclay ML, Frampton CM, et al. Perianal disease predicts changes in Crohn?s disease phenotype-results of a population-based study of inflammatory bowel disease phenotype. Am J Gastroenterol. 2008;103:3082-3093.
88. Solberg IC, Vatn MH, Hoie 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.
89. Wolters FL, Russel MG, Sijbrandij J, et al. Phenotype at diagnosis predicts recurrence rates in Crohn?s disease. Gut. 2006;55:1124-1130.
90. Henriksen M, Jahnsen J, Lygren I, et al. Are there any differences in phenotype or disease course between familial and sporadic cases of inflammatory bowel disease?. Results of a population-based follow-up study. Am J Gastroenterol. 2007;102:1955-1963.
91. Hoie O, Wolters F, Riis L, et al. Ulcerative colitis: patient characteristics may predict 10-yr disease recurrence in a European-wide populationbased cohort. Am J Gastroenterol. 2007;102:1692-1701.
92. Hoie O, Wolters FL, Riis L, et al. Low colectomy rates in ulcerative colitis in an unselected European cohort followed for 10 years. Gastroenterology. 2007;132:507-515.
93. Gower-Rousseau C, Dauchet L, Vernier-Massouille G, et al. The natural history of pediatric ulcerative colitis: a population-based cohort study. Am J Gastroenterol. 2009;104:2080-2088.
94. Allez M, Lemann M, Bonnet J, et al. Long term outcome of patients with active Crohn?s disease exhibiting extensive and deep ulcerations at colonoscopy. Am J Gastroenterol. 2002;97:947-953.
95. Carbonnel F, Gargouri D, Lemann M, et al. Predictive factors of outcome of intensive intravenous treatment for attacks of ulcerative colitis. Aliment Pharmacol Ther. 2000;14:273-279.
96. Allison J, Herrinton LJ, Liu L, et al. Natural history of severe ulcerative colitis in a community-based health plan. Clin Gastroenterol Hepatol. 2008;6:999-1003.
97. Niewiadomski O, Studd C, Hair C, et al. A prospective population based cohort of inflammatory bowel disease in the biologics era-Disease course and predictors of severity. J Gastroenterol Hepatol. 2015;30: 1346-1353.
98. Tinsley A, Naymagon S, Mathers B, et al. Early readmission in patients hospitalized for ulcerative colitis: incidence and risk factors. Scand J Gastroenterol. 2015;50:1103-1109.
99. Dias CC, Rodrigues PP, Costa-Pereira AD, et al. Clinical predictors of colectomy in patients with ulcerative colitis: systematic review and metaanalysis of cohort studies. J Crohns Colitis. 2015;9:156-163.
100. Canas-Ventura A, Marquez L, Ricart E, et al. Risk of colectomy in patients with ulcerative colitis under thiopurine treatment. J Crohns Colitis. 2014;8:1287-1293.
101. Samaan MA, Bagi P, Vande Casteele N, et al. An update on anti-TNF agents in ulcerative colitis. Gastroenterol Clin North Am. 2014;43:479-494.
102. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn?s disease. N Engl J Med. 1999;340: 1398-1405.
103. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn?s disease. N Engl J Med. 2004;350: 876-885.
104. Dulai PS, Mosli M, Khanna R, et al. Vedolizumab for the treatment of moderately to severely active ulcerative colitis. Pharmacotherapy. 2015; 35:412-423.
105. Menting SP, van den Reek JM, Baerveldt EM, et al. The correlation of clinical efficacy, serum trough levels and antidrug antibodies in ustekinumab-Treated patients with psoriasis in a clinical-practice setting. Br J Dermatol. 2015.
106. Dulai PS, Fisher ES, Rothstein RI. How may the transition to valuebased payment influence gastroenterology: threat or opportunity?. Clin Gastroenterol Hepatol. 2012;10:609-611.
107. Rex DK, Schoenfeld PS, Cohen J, et al. Quality indicators for colonoscopy. Am J Gastroenterol. 2015;110:72-90.
108. Corley DA, Jensen CD, Marks AR, et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. 2014;370:1298-1306.
109. Dulai PS, Siegel CA. The risk of malignancy associated with the use of biological agents in patients with inflammatory bowel disease. Gastroenterol Clin North Am. 2014;43:525-541.
110. Dulai PS, Siegel CA, Dubinsky MC. Balancing and communicating the risks and benefits of biologics in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2013;19:2927-2936.
111. Dulai PS, Thompson KD, Blunt HB, et al. Risks of serious infection or lymphoma with anti-Tumor necrosis factor therapy for pediatric inflammatory bowel disease: a systematic review. Clin Gastroenterol Hepatol. 2014;12:1443-1451; quiz e88-9.
112. Siegel CA. Shared decision making in inflammatory bowel disease: helping patients understand the tradeoffs between treatment options. Gut. 2012;61:459-465.
113. Siegel CA, Horton H, Siegel LS, et al. Su1312 A Validated web-based patient Communication tool to display individualized Crohn?s disease predicted outcomes based on clinical, serologic and Genetic variables. Gastroenterology. 2015;146:S-433-S-434.
114. Siegel CA, Siegel LS, Hyams JS, et al. 1108 A Prediction tool to help children with Crohn?s disease and their parents understand individualized risks of disease complications and response to therapy. Gastroenterology. 2014;136:A-172.
115. Tracey D, Klareskog L, Sasso EH, et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117:244-279.
116. Yarur AJ, Jain A, Sussman DA, et al. The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study. Gut. 2016;65:249-255.
117. Boland BS, Rivera-Nieves J, Jain A, et al. 535 Soluble MAdCAM-1: a potential Biomarker for response to vedolizumab. Gastroenterology. 2015;148:S-106-S-107.
118. Shah ED, Siegel CA, Chong K, et al. Patients with Crohn?s disease are more likely to remain on biologics than Immunomodulators: a metaanalysis of treatment durability. Dig Dis Sci. 2015;60:2408-2418.
119. Vande Casteele N, Sandborn WJ. IBD: Indication extrapolation for anti-TNF biosimilars. Nat Rev Gastroenterol Hepatol. 2015;12:373-374.