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Updates in Healthcare Maintenance and Monitoring of Children with Inflammatory Bowel Disease in the Era of Biologic Therapies

  • Trusha PatelEmail author
  • Andrew B. Grossman
Pediatric Gastroenterology (SA Saeed and K Sandberg, Section Editors)
  • 8 Downloads
Part of the following topical collections:
  1. Topical Collection on Pediatric Gastroenterology

Abstract

Purpose of Review

As the therapeutic armamentarium for the management of pediatric inflammatory bowel disease (IBD) expands, it is increasingly challenging for pediatric gastroenterologists and pediatric primary care providers to stay abreast of the available therapies and the associated side effects, required monitoring, and specific health maintenance needs for these patients. Here, we review the currently available therapies and general treatment strategies for the management of pediatric IBD, along with clinical considerations in the context of general pediatric care.

Recent Findings

The number of therapies for the management of IBD has grown rapidly in recent years. While pediatric providers have become adept with the use of anti-tumor necrosis factor-alpha therapies, and large safety registries have helped us understand the risks of these biologic agents, there is much left to learn about the pediatric use of newer therapies, such as vedolizumab, ustekinumab, and tofacitinib.

Summary

Biologic therapies and other targeted anti-inflammatory therapies are increasingly used in children with IBD. Pediatric primary care providers and pediatric gastroenterologists must be aware of the risks, benefits, and additional implications of these therapies. Vaccination strategies, recognition and management of routine or opportunistic infections, assessment of rashes, and cancer screening represent areas of particular importance in these children.

Keywords

Inflammatory bowel disease (IBD) Infliximab Adalimumab Ustekinumab Vedolizumab Tofacitinib 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Levine A, Griffiths A, Markowitz J, Wilson DC, Turner D, Russell RK, et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis. 2011;17(6):1314–21.CrossRefGoogle Scholar
  2. 2.
    Kappelman MD, Moore KR, Allen JK, Cook SF. Recent trends in the prevalence of Crohn’s disease and ulcerative colitis in a commercially insured US population. Dig Dis Sci. 2013;58(2):519–25.PubMedCrossRefGoogle Scholar
  3. 3.
    Baldassano RN, Piccoli DA. Inflammatory bowel disease in pediatric and adolescent patients. Gastroenterol Clin N Am. 1999;28(2):445–58.CrossRefGoogle Scholar
  4. 4.
    • Benchimol EI, Bernstein CN, Bitton A, Carroll MW, Singh H, Otley AR, et al. Trends in epidemiology of pediatric inflammatory bowel disease in Canada: distributed network analysis of multiple population-based provincial health administrative databases. Am J Gastroenterol. 2017;112(7):1120–34 This study serves as an important epidemiologic investigation into the rising prevalence of pediatric inflammatory bowel disease in a population with high incidence. In particular, it highlights the rapid increase in incidence in very young children.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Benchimol EI, Fortinsky KJ, Gozdyra P, Van den Heuvel M, Van Limbergen J, Griffiths AM. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis. 2011;17(1):423–39.PubMedCrossRefGoogle Scholar
  6. 6.
    Degraeuwe PL, Beld MP, Ashorn M, Canani RB, Day AS, Diamanti A, et al. Faecal calprotectin in suspected paediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2015;60(3):339–46.PubMedCrossRefGoogle Scholar
  7. 7.
    Ruemmele FM, Veres G, Kolho KL, Griffiths A, Levine A, Escher JC, et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis. 2014;8(10):1179–207.PubMedCrossRefGoogle Scholar
  8. 8.
    Bouguen G, Levesque BG, Feagan BG, Kavanaugh A, Peyrin-Biroulet L, Colombel JF, et al. Treat to target: a proposed new paradigm for the management of Crohn’s disease. Clin Gastroenterol Hepatol. 2015;13(6):1042–50 e2.CrossRefGoogle Scholar
  9. 9.
    Baert F, Moortgat L, Van Assche G, Caenepeel P, Vergauwe P, De Vos M, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138(2):463–8 quiz e10–1.PubMedCrossRefGoogle Scholar
  10. 10.
    Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I, Van Assche G, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis. 2009;15(9):1295–301.PubMedCrossRefGoogle Scholar
  11. 11.
    Walters TD, Kim MO, Denson LA, Griffiths AM, Dubinsky M, Markowitz J, et al. Increased effectiveness of early therapy with anti-tumor necrosis factor-alpha vs an immunomodulator in children with Crohn’s disease. Gastroenterology. 2014;146(2):383–91.PubMedCrossRefGoogle Scholar
  12. 12.
    Kang B, Choi SY, Kim HS, Kim K, Lee YM, Choe YH. Mucosal healing in paediatric patients with moderate-to-severe luminal Crohn’s disease under combined immunosuppression: escalation versus early treatment. J Crohns Colitis. 2016;10(11):1279–86.PubMedCrossRefGoogle Scholar
  13. 13.
    Choi J, Kang B, Kim MJ, Sohn I, Lee HJ, Choe YH. Early infliximab yields superior long-term effects on linear growth in pediatric Crohn’s disease patients. Gut Liver. 2018;12(3):255–62.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    D’Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet. 2008;371(9613):660–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Vande Casteele N, Ferrante M, Van Assche G, Ballet V, Compernolle G, Van Steen K, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148(7):1320–9 e3.CrossRefGoogle Scholar
  16. 16.
    Vande Casteele N, Gils A, Singh S, Ohrmund L, Hauenstein S, Rutgeerts P, et al. Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am J Gastroenterol. 2013;108(6):962–71.PubMedCrossRefGoogle Scholar
  17. 17.
    Adedokun OJ, Sandborn WJ, Feagan BG, Rutgeerts P, Xu Z, Marano CW, et al. Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. Gastroenterology. 2014;147(6):1296–307 e5.PubMedCrossRefGoogle Scholar
  18. 18.
    • Papamichael K, Chachu KA, Vajravelu RK, Vaughn BP, Ni J, Osterman MT, et al. Improved long-term outcomes of patients with inflammatory bowel disease receiving proactive compared with reactive monitoring of serum concentrations of infliximab. Clin Gastroenterol Hepatol. 2017;15(10):1580–8 e3 This study provides important insight into the importance of proactive drug monitoring, which is being adopted in clinical practice with increasing frequency.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    •• Feuerstein JD, Nguyen GC, Kupfer SS, Falck-Ytter Y, Singh S. American Gastroenterological Association Institute Clinical Guidelines. American Gastroenterological Association Institute Guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology. 2017;153(3):827–34 These societal guidelines are and important summary of the available data on therapeutic drug monitoring in IBD, particularly in reference to anti-TNF therapies.PubMedCrossRefGoogle Scholar
  20. 20.
    Day AS, Gulati AS, Patel N, Boyle B, Park KT, Saeed SA. The role of combination therapy in pediatric inflammatory bowel disease: a clinical report from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018;66(2):361–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Borrelli O, Cordischi L, Cirulli M, Paganelli M, Labalestra V, Uccini S, et al. Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn’s disease: a randomized controlled open-label trial. Clin Gastroenterol Hepatol. 2006;4(6):744–53.PubMedCrossRefGoogle Scholar
  22. 22.
    • Lane ER, Lee D, Suskind DL. Dietary therapies in pediatric inflammatory bowel disease: an evolving inflammatory bowel disease paradigm. Gastroenterol Clin N Am. 2017;46(4):731–44This article provides a thorough review of the dietary therapies that are part of the therapeutic approach for pediatric inflammatory bowel disease and may serve as a good supplement to our current review, which focuses primarily on medical.Google Scholar
  23. 23.
    Green N, Miller T, Suskind D, Lee D. A review of dietary therapy for IBD and a vision for the future. Nutrients. 2019;11(5).PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):309–18.PubMedCrossRefGoogle Scholar
  25. 25.
    Ardura MI, Kim SC. Infectious complications of pediatric inflammatory bowel disease. In: Mamula P, Grossman AB, Baldassano RN, Kelsen JR, Markowitz JE, editors. Pediatric inflammatory bowel disease. 3rd ed. Cham: Springer International Publishing; 2017.Google Scholar
  26. 26.
    DeFilippis EM, Sockolow R, Barfield E. Health care maintenance for the pediatric patient with inflammatory bowel disease. Pediatrics. 2016;138(3).PubMedCrossRefGoogle Scholar
  27. 27.
    deBruyn JC, Hilsden R, Fonseca K, Russell ML, Kaplan GG, Vanderkooi O, et al. Immunogenicity and safety of influenza vaccination in children with inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(1):25–33.PubMedCrossRefGoogle Scholar
  28. 28.
    Mamula P, Markowitz JE, Piccoli DA, Klimov A, Cohen L, Baldassano RN. Immune response to influenza vaccine in pediatric patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007;5(7):851–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Jacobson DL, Bousvaros A, Ashworth L, Carey R, Shrier LA, Burchett SK, et al. Immunogenicity and tolerability to human papillomavirus-like particle vaccine in girls and young women with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(7):1441–9.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Banaszkiewicz A, Targonska B, Kowalska-Duplaga K, Karolewska-Bochenek K, Sieczkowska A, Gawronska A, et al. Immunogenicity of 13-valent pneumococcal conjugate vaccine in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2015;21(7):1607–14.PubMedCrossRefGoogle Scholar
  31. 31.
    Benchimol EI, Hawken S, Kwong JC, Wilson K. Safety and utilization of influenza immunization in children with inflammatory bowel disease. Pediatrics. 2013;131(6):e1811–20.PubMedCrossRefGoogle Scholar
  32. 32.
    Rufo PA, Denson LA, Sylvester FA, Szigethy E, Sathya P, Lu Y, et al. Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations. J Pediatr Gastroenterol Nutr. 2012;55(1):93–108.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Sands BE, Cuffari C, Katz J, Kugathasan S, Onken J, Vitek C, et al. Guidelines for immunizations in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2004;10(5):677–92.PubMedCrossRefGoogle Scholar
  34. 34.
    • Click B, Regueiro M. Managing risks with biologics. Curr Gastroenterol Rep. 2019;21(2):1 This recent review provides a thoughtful overview of the risks and considerations that clinicians must be aware of in patients with IBD being treated with biologic therapies. It is one of the few reviews that addressess the risks of newer biologic thereapies.PubMedCrossRefGoogle Scholar
  35. 35.
    Wichmann A, Krugliak Cleveland N, Rubin DT. Safety and efficacy of live measles vaccine administered to a Crohn’s disease patient receiving vedolizumab. Am J Gastroenterol. 2016;111(4):577.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Takeda Pharmaceuticals America, Inc. Entyvio (vedolizumab) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125476s000lbl.pdf. Revised May 2014. Accessed June 4, 2019.
  37. 37.
    Am Acad Pediatr Immunization and Other Considerations in Immunocompromised Children. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. American Academy of Pediatrics; 2018; 72–91.Google Scholar
  38. 38.
    General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP). https://cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html. Revised April 20, 2017. Accessed June 9, 2019. [Internet].
  39. 39.
    Monto AS. Viral respiratory infections in the community: epidemiology, agents, and interventions. Am J Med. 1995;99(6B):24S–7S.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Gruber C, Keil T, Kulig M, Roll S, Wahn U, Wahn V, et al. History of respiratory infections in the first 12 yr among children from a birth cohort. Pediatr Allergy Immunol. 2008;19(6):505–12.PubMedCrossRefGoogle Scholar
  41. 41.
    Tinsley A, Navabi S, Williams ED, Liu G, Kong L, Coates MD, et al. Erratum to increased risk of influenza and influenza-related complications among 140,480 patients with inflammatory bowel disease. Inflamm Bowel Dis. 2018.Google Scholar
  42. 42.
    Long MD, Martin C, Sandler RS, Kappelman MD. Increased risk of pneumonia among patients with inflammatory bowel disease. Am J Gastroenterol. 2013;108(2):240–8.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Cullen G, Baden RP, Cheifetz AS. Varicella zoster virus infection in inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(12):2392–403.PubMedCrossRefGoogle Scholar
  44. 44.
    Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Price S, et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT registry. Am J Gastroenterol. 2012;107(9):1409–22.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Dulai PS, Thompson KD, Blunt HB, Dubinsky MC, Siegel CA. 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(9):1443–51 quiz e88–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Singh S, Facciorusso A, Dulai PS, Jairath V, Sandborn WJ. Comparative risk of serious infections with biologic and/or immunosuppressive therapy in patients with inflammatory bowel diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019.Google Scholar
  47. 47.
    Ford AC, Peyrin-Biroulet L. Opportunistic infections with anti-tumor necrosis factor-alpha therapy in inflammatory bowel disease: meta-analysis of randomized controlled trials. Am J Gastroenterol. 2013;108(8):1268–76.PubMedCrossRefGoogle Scholar
  48. 48.
    Gong SS, Fan YH, Han QQ, Lv B, Xu Y. Nested case-control study on risk factors for opportunistic infections in patients with inflammatory bowel disease. World J Gastroenterol. 2019;25(18):2240–50.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Bonovas S, Fiorino G, Allocca M, Lytras T, Nikolopoulos GK, Peyrin-Biroulet L, et al. Biologic therapies and risk of infection and malignancy in patients with inflammatory bowel disease: a systematic review and network meta-analysis. Clin Gastroenterol Hepatol. 2016;14(10):1385–97 e10.PubMedCrossRefGoogle Scholar
  50. 50.
    • Colombel JF, Sands BE, Rutgeerts P, Sandborn W, Danese S, D’Haens G, et al. The safety of vedolizumab for ulcerative colitis and Crohn’s disease. Gut. 2017;66(5):839–51 This study highlights the favorable safety profile of vedolizumab therapy in patients with IBD. It provides a comprehensive review of adverse events of interest and provides clinicians with data from a large cohort of patients that can aid clinical decision-making.PubMedCrossRefGoogle Scholar
  51. 51.
    Conrad MA, Stein RE, Maxwell EC, Albenberg L, Baldassano RN, Dawany N, et al. Vedolizumab therapy in severe pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2016;22(10):2425–31.PubMedCrossRefGoogle Scholar
  52. 52.
    Singh N, Rabizadeh S, Jossen J, Pittman N, Check M, Hashemi G, et al. Multi-center experience of vedolizumab effectiveness in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2016;22(9):2121–6.PubMedCrossRefGoogle Scholar
  53. 53.
    • Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375(20):1946–60 This study reviews the clinical trial data leading to the approval for ustekinumab for the induction and maintenance of Crohn’s disease and provides important insight into the efficacy and safety of this therapy.PubMedCrossRefGoogle Scholar
  54. 54.
    Hanauer SB, Sandborn WJ, Feagan BG, Gasink C, Jacobstein D, Zou B, et al. IM-UNITI: 3 year efficacy, safety, and immunogenicity of ustekinumab treatment of Crohn’s disease. J Crohns Colitis. 2019.Google Scholar
  55. 55.
    • Sandborn WJ, Su C, Sands BE, D’Haens GR, Vermeire S, Schreiber S, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376(18):1723–36 This study reviews the clinical trial data leading to the approval for tofacitinib for the induction and maintenance of ulcerative colitis and provides important insight into the efficacy and safety of this therapy.PubMedCrossRefGoogle Scholar
  56. 56.
    Sandborn WJ, Panes J, D’Haens GR, Sands BE, Su C, Moscariello M, et al. Safety of tofacitinib for treatment of ulcerative colitis, based on 4.4 years of data from global clinical trials. Clin Gastroenterol Hepatol. 2018.Google Scholar
  57. 57.
    Veereman-Wauters G, de Ridder L, Veres G, Kolacek S, Fell J, Malmborg P, et al. Risk of infection and prevention in pediatric patients with IBD: ESPGHAN IBD Porto Group commentary. J Pediatr Gastroenterol Nutr. 2012;54(6):830–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2014;8(6):443–68.PubMedCrossRefGoogle Scholar
  59. 59.
    Rahier JF, Ben-Horin S, Chowers Y, Conlon C, De Munter P, D’Haens G, et al. European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2009;3(2):47–91.PubMedCrossRefGoogle Scholar
  60. 60.
    Landsman MJ, Sultan M, Stevens M, Charabaty A, Mattar MC. Diagnosis and management of common gastrointestinal tract infectious diseases in ulcerative colitis and Crohn’s disease patients. Inflamm Bowel Dis. 2014;20(12):2503–10.PubMedCrossRefGoogle Scholar
  61. 61.
    Shane AL, Mody RK, Crump JA, Tarr PI, Steiner TS, Kotloff K, et al. Infectious Diseases Society of America Clinical Practice Guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017;65(12):1963–73.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Am Acad Pediatr Summaries of Infectious Diseases. In: Kimberlin DW BM, Jackson MA, Long SS, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. American Academy of Pediatrics; 2018; 711–718.Google Scholar
  63. 63.
    Ardura MI, Toussi SS, Siegel JD, Lu Y, Bousvaros A, Crandall W. NASPGHAN clinical report: surveillance, diagnosis, and prevention of infectious diseases in pediatric patients with inflammatory bowel disease receiving tumor necrosis factor-alpha inhibitors. J Pediatr Gastroenterol Nutr. 2016;63(1):130–55.PubMedCrossRefGoogle Scholar
  64. 64.
    •• Hyams JS, Dubinsky MC, Baldassano RN, Colletti RB, Cucchiara S, Escher J, et al. Infliximab is not associated with increased risk of malignancy or hemophagocytic lymphohistiocytosis in pediatric patients with inflammatory bowel disease. Gastroenterology. 2017;152(8):1901–14 e3 This important study is the largest study examining the safety of anti-TNFα therapies in pediatric IBD to date. Its findings provide valuable information for clinicians to discuss with their patients when considering the risks of infliximab and thiopurines in the management of pediatric IBD.PubMedCrossRefGoogle Scholar
  65. 65.
    Axelrad JE, Joelson A, Green PHR, Lawlor G, Lichtiger S, Cadwell K, et al. Enteric infections are common in patients with flares of inflammatory bowel disease. Am J Gastroenterol. 2018;113(10):1530–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Sokol H, Lalande V, Landman C, Bourrier A, Nion-Larmurier I, Rajca S, et al. Clostridium difficile infection in acute flares of inflammatory bowel disease: a prospective study. Dig Liver Dis. 2017;49(6):643–6.PubMedCrossRefGoogle Scholar
  67. 67.
    Vavricka SR, Schoepfer A, Scharl M, Lakatos PL, Navarini A, Rogler G. Extraintestinal manifestations of inflammatory bowel disease. Inflamm Bowel Dis. 2015;21(8):1982–92.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Greuter T, Navarini A, Vavricka SR. Skin manifestations of inflammatory bowel disease. Clin Rev Allergy Immunol. 2017;53(3):413–27.PubMedCrossRefGoogle Scholar
  69. 69.
    Beaugerie L, Itzkowitz SH. Cancers complicating inflammatory bowel disease. N Engl J Med. 2015;372(15):1441–52.PubMedCrossRefGoogle Scholar
  70. 70.
    Annese V, Beaugerie L, Egan L, Biancone L, Bolling C, Brandts C, et al. European evidence-based consensus: inflammatory bowel disease and malignancies. J Crohns Colitis. 2015;9(11):945–65.PubMedCrossRefGoogle Scholar
  71. 71.
    Singh H, Nugent Z, Demers AA, Bernstein CN. Increased risk of nonmelanoma skin cancers among individuals with inflammatory bowel disease. Gastroenterology. 2011;141(5):1612–20.PubMedCrossRefGoogle Scholar
  72. 72.
    Janssen Biotech, Inc. Remicade (infliximab) [package insert]. U.S. Food and Drug Administration Website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/103772s5359lbl.pdf. Revised November 2013. Accessed June 13, 2019.
  73. 73.
    Janssen Biotech, Inc. STELARA (ustekinumab) [package insert]. U.S. Food and Drug Administration Website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761044Orig1s000Lbl.pdf. Revised September 2016. Accessed June 13, 2019.
  74. 74.
    Dayan JR, Dolinger M, Benkov K, Dunkin D, Jossen J, Lai J, et al. Real world experience with ustekinumab in children and young adults at a tertiary care pediatric inflammatory bowel disease center. J Pediatr Gastroenterol Nutr. 2019.Google Scholar
  75. 75.
    Jess T, Loftus EV Jr, Velayos FS, Harmsen WS, Zinsmeister AR, Smyrk TC, et al. Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota. Gastroenterology. 2006;130(4):1039–46.PubMedCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Gastroenterology, Hepatology and NutritionChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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