Skip to main content
SpringerLink
Log in

Biologic Therapy in Pediatric Inflammatory Bowel Disease

  • Chapter
  • First Online:
Treatment of Inflammatory Bowel Disease with Biologics

Abstract

The incidence of pediatric inflammatory bowel disease (IBD) has risen over the past several decades and therapeutic strategies continue to evolve. Many unique considerations must be taken into account when selecting the optimal therapy for a pediatric IBD patient, including the effect of therapy on growth parameters, the cummulative or long-term adverse effects of treatments, and the inherently longer duration of therapy give the young age at diagnosis. Biologic agents have been used to treat pediatric IBD for several decades. This chapter reviews the biologic agents currently used to treat this population, the indications for use in pediatric Crohn’s disease (CD) and ulcerative colitis (UC), outcomes associated with these medications, including impact on growth and bone health, and adverse events, specfically malignancy risks. Strategies and recommendations for vaccination of peidatric IBD patients receiving biologic therapy are also reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. 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;17:423–39.

    Article  PubMed  Google Scholar 

  2. Heyman MB, Kirschner BS, Gold BD, et al. Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry. J Pediatr. 2005;146:35–40.

    Article  PubMed  Google Scholar 

  3. Van Limbergen J, Russell RK, Drummond HE, et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology. 2008;135:1114–22.

    Article  PubMed  Google Scholar 

  4. Kugathasan S, Werlin SL, Martinez A, Rivera MT, Heikenen JB, Binion DG. Prolonged duration of response to infliximab in early but not late pediatric Crohn’s disease. Am J Gastroenterol. 2000;95:3189–94.

    Article  CAS  PubMed  Google Scholar 

  5. Baldassano R, Braegger CP, Escher JC, et al. Infliximab (REMICADE) therapy in the treatment of pediatric Crohn’s disease. Am J Gastroenterol. 2003;98:833–8.

    Article  CAS  PubMed  Google Scholar 

  6. Cezard JP, Nouaili N, Talbotec C, et al. A prospective study of the efficacy and tolerance of a chimeric antibody to tumor necrosis factors (remicade) in severe pediatric crohn disease. J Pediatr Gastroenterol Nutr. 2003;36:632–6.

    Article  CAS  PubMed  Google Scholar 

  7. Ruemmele FM, Lachaux A, Cezard JP, et al. Efficacy of infliximab in pediatric Crohn’s disease: a randomized multicenter open-label trial comparing scheduled to on demand maintenance therapy. Inflamm Bowel Dis. 2009;15:388–94.

    Article  PubMed  Google Scholar 

  8. Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. Gastroenterology. 2007;132:863–73. quiz 1165-6.

    Article  CAS  PubMed  Google Scholar 

  9. Hyams J, Walters TD, Crandall W, et al. Safety and efficacy of maintenance infliximab therapy for moderate-to-severe Crohn’s disease in children: REACH open-label extension. Curr Med Res Opin. 2011;27:651–62.

    Article  CAS  PubMed  Google Scholar 

  10. de Ridder L, Rings EH, Damen GM, et al. Infliximab dependency in pediatric Crohn’s disease: long-term follow-up of an unselected cohort. Inflamm Bowel Dis. 2008;14:353–8.

    Article  PubMed  Google Scholar 

  11. Crombe V, Salleron J, Savoye G, et al. Long-term outcome of treatment with infliximab in pediatric-onset Crohn’s disease: a population-based study. Inflamm Bowel Dis. 2011;17:2144–52.

    Article  PubMed  Google Scholar 

  12. Hyams JS, Lerer T, Griffiths A, et al. Long-term outcome of maintenance infliximab therapy in children with Crohn’s disease. Inflamm Bowel Dis. 2009;15:816–22.

    Article  PubMed  Google Scholar 

  13. Grover Z, Biron R, Carman N, Lewindon P. Predictors of response to infliximab in children with luminal Crohn’s disease. J Crohns Colitis. 2014;8:739–46.

    Article  PubMed  Google Scholar 

  14. Kelsen JR, Grossman AB, Pauly-Hubbard H, Gupta K, Baldassano RN, Mamula P. Infliximab therapy in pediatric patients 7 years of age and younger. J Pediatr Gastroenterol Nutr. 2014;59:758–62.

    Article  CAS  PubMed  Google Scholar 

  15. Crandall W, Hyams J, Kugathasan S, et al. Infliximab therapy in children with concurrent perianal Crohn disease: observations from REACH. J Pediatr Gastroenterol Nutr. 2009;49:183–90.

    Article  CAS  PubMed  Google Scholar 

  16. Lionetti P, Bronzini F, Salvestrini C, et al. Response to infliximab is related to disease duration in paediatric Crohn’s disease. Aliment Pharmacol Ther. 2003;18:425–31.

    Article  CAS  PubMed  Google Scholar 

  17. Dupont-Lucas C, Dabadie A, Alberti C, Ruemmele FM. Predictors of response to infliximab in paediatric perianal Crohn’s disease. Aliment Pharmacol Ther. 2014;40:917–29.

    Article  CAS  PubMed  Google Scholar 

  18. de Zoeten EF, Pasternak BA, Mattei P, Kramer RE, Kader HA. Diagnosis and treatment of perianal Crohn disease: NASPGHAN clinical report and consensus statement. J Pediatr Gastroenterol Nutr. 2013;57:401–12.

    Article  PubMed  Google Scholar 

  19. Mamula P, Markowitz JE, Brown KA, Hurd LB, Piccoli DA, Baldassano RN. Infliximab as a novel therapy for pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr. 2002;34:307–11.

    Article  CAS  PubMed  Google Scholar 

  20. Mamula P, Markowitz JE, Cohen LJ, von Allmen D, Baldassano RN. Infliximab in pediatric ulcerative colitis: two-year follow-up. J Pediatr Gastroenterol Nutr. 2004;38:298–301.

    Article  CAS  PubMed  Google Scholar 

  21. Eidelwein AP, Cuffari C, Abadom V, Oliva-Hemker M. Infliximab efficacy in pediatric ulcerative colitis. Inflamm Bowel Dis. 2005;11:213–8.

    Article  PubMed  Google Scholar 

  22. McGinnis JK, Murray KF. Infliximab for ulcerative colitis in children and adolescents. J Clin Gastroenterol. 2008;42:875–9.

    Article  CAS  PubMed  Google Scholar 

  23. Hyams JS, Lerer T, Griffiths A, et al. Outcome following infliximab therapy in children with ulcerative colitis. Am J Gastroenterol. 2010;105:1430–6.

    Article  CAS  PubMed  Google Scholar 

  24. Fanjiang G, Russell GH, Katz AJ. Short- and long-term response to and weaning from infliximab therapy in pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr. 2007;44:312–7.

    Article  CAS  PubMed  Google Scholar 

  25. Turner D, Walsh CM, Benchimol EI, et al. Severe paediatric ulcerative colitis: incidence, outcomes and optimal timing for second-line therapy. Gut. 2008;57:331–8.

    Article  CAS  PubMed  Google Scholar 

  26. Turner D, Mack D, Leleiko N, et al. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology. 2010;138:2282–91.

    Article  CAS  PubMed  Google Scholar 

  27. Falaiye TO, Mitchell KR, Lu Z, et al. Outcomes following infliximab therapy for pediatric patients hospitalized with refractory colitis-predominant IBD. J Pediatr Gastroenterol Nutr. 2014;58:213–9.

    Article  PubMed  Google Scholar 

  28. Hyams J, Damaraju L, Blank M, et al. Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol. 2012;10:391–9.e1.

    Article  CAS  PubMed  Google Scholar 

  29. Adedokun OJ, Xu Z, Padgett L, et al. Pharmacokinetics of infliximab in children with moderate-to-severe ulcerative colitis: results from a randomized, multicenter, open-label, phase 3 study. Inflamm Bowel Dis. 2013;19:2753–62.

    Article  PubMed  Google Scholar 

  30. Noe JD, Pfefferkorn M. Short-term response to adalimumab in childhood inflammatory bowel disease. Inflamm Bowel Dis. 2008;14:1683–7.

    Article  PubMed  Google Scholar 

  31. Wyneski MJ, Green A, Kay M, Wyllie R, Mahajan L. Safety and efficacy of adalimumab in pediatric patients with Crohn disease. J Pediatr Gastroenterol Nutr. 2008;47:19–25.

    Article  CAS  PubMed  Google Scholar 

  32. Cozijnsen M, Duif V, Kokke F, et al. Adalimumab therapy in children with Crohn disease previously treated with infliximab. J Pediatr Gastroenterol Nutr. 2015;60:205–10.

    Article  CAS  PubMed  Google Scholar 

  33. Fumery M, Jacob A, Sarter H, et al. Efficacy and safety of adalimumab after infliximab failure in pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2015;60:744–8.

    Article  CAS  PubMed  Google Scholar 

  34. Rosh JR, Lerer T, Markowitz J, et al. Retrospective evaluation of the safety and effect of adalimumab therapy (RESEAT) in pediatric Crohn’s disease. Am J Gastroenterol. 2009;104:3042–9.

    Article  CAS  PubMed  Google Scholar 

  35. Viola F, Civitelli F, Di Nardo G, et al. Efficacy of adalimumab in moderate-to-severe pediatric Crohn’s disease. Am J Gastroenterol. 2009;104:2566–71.

    Article  CAS  PubMed  Google Scholar 

  36. Hyams JS, Griffiths A, Markowitz J, et al. Safety and efficacy of adalimumab for moderate to severe Crohn’s disease in children. Gastroenterology. 2012;143:365–74.e2.

    Article  CAS  PubMed  Google Scholar 

  37. Dubinsky MC, Rosh J, Faubion WA Jr, et al. Efficacy and safety of escalation of adalimumab therapy to weekly dosing in pediatric patients with Crohn’s disease. Inflamm Bowel Dis. 2016;22:886–93.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Faubion WA, Dubinsky M, Ruemmele FM, et al. Long-term efficacy and safety of adalimumab in pediatric patients with Crohn’s disease. Inflamm Bowel Dis. 2017;23:453–60.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Volonaki E, Mutalib M, Kiparissi F, Shah N, Lindley KJ, Elawad M. Adalimumab as a second-line biological therapy in children with refractory ulcerative colitis. Eur J Gastroenterol Hepatol. 2015;27:1425–8.

    Article  CAS  PubMed  Google Scholar 

  40. Park KT, Sin A, Wu M, Bass D, Bhattacharya J. Utilization trends of anti-TNF agents and health outcomes in adults and children with inflammatory bowel diseases: a single-center experience. Inflamm Bowel Dis. 2014;20:1242–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Markowitz J, Grancher K, Rosa J, Aiges H, Daum F. Growth failure in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1993;16:373–80.

    Article  CAS  PubMed  Google Scholar 

  42. Motil KJ, Grand RJ, Davis-Kraft L, Ferlic LL, Smith EO. Growth failure in children with inflammatory bowel disease: a prospective study. Gastroenterology. 1993;105:681–91.

    Article  CAS  PubMed  Google Scholar 

  43. Heuschkel R, Salvestrini C, Beattie RM, Hildebrand H, Walters T, Griffiths A. Guidelines for the management of growth failure in childhood inflammatory bowel disease. Inflamm Bowel Dis. 2008;14:839–49.

    Article  PubMed  Google Scholar 

  44. Ballinger AB, Azooz O, El-Haj T, Poole S, Farthing MJ. Growth failure occurs through a decrease in insulin-like growth factor 1 which is independent of undernutrition in a rat model of colitis. Gut. 2000;46:694–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kleinman RE, Baldassano RN, Caplan A, et al. Nutrition support for pediatric patients with inflammatory bowel disease: a clinical report of the North American Society for Pediatric Gastroenterology, Hepatology And Nutrition. J Pediatr Gastroenterol Nutr. 2004;39:15–27.

    Article  PubMed  Google Scholar 

  46. Wong SC, Macrae VE, McGrogan P, Ahmed SF. The role of pro-inflammatory cytokines in inflammatory bowel disease growth retardation. J Pediatr Gastroenterol Nutr. 2006;43:144–55.

    Article  CAS  PubMed  Google Scholar 

  47. Walters TD, Gilman AR, Griffiths AM. Linear growth improves during infliximab therapy in children with chronically active severe Crohn’s disease. Inflamm Bowel Dis. 2007;13:424–30.

    Article  PubMed  Google Scholar 

  48. Malik S, Ahmed SF, Wilson ML, et al. The effects of anti-TNF-alpha treatment with adalimumab on growth in children with Crohn’s disease (CD). J Crohns Colitis. 2012;6:337–44.

    Article  CAS  PubMed  Google Scholar 

  49. Cameron FL, Altowati MA, Rogers P, et al. Disease status and pubertal stage predict improved growth in antitumor necrosis factor therapy for pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2017;64:47–55.

    Article  CAS  PubMed  Google Scholar 

  50. Malik S, Wong SC, Bishop J, et al. Improvement in growth of children with Crohn disease following anti-TNF-alpha therapy can be independent of pubertal progress and glucocorticoid reduction. J Pediatr Gastroenterol Nutr. 2011;52:31–7.

    Article  CAS  PubMed  Google Scholar 

  51. DeBoer MD, Thayu M, Griffin LM, et al. Increases in sex hormones during anti-tumor necrosis factor alpha therapy in adolescents with Crohn’s disease. J Pediatr. 2016;171:146–52.e1-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Vespasiani Gentilucci U, Caviglia R, Picardi A, et al. Infliximab reverses growth hormone resistance associated with inflammatory bowel disease. Aliment Pharmacol Ther. 2005;21:1063–71.

    Article  CAS  PubMed  Google Scholar 

  53. Sylvester FA, Wyzga N, Hyams JS, et al. Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease. Inflamm Bowel Dis. 2007;13:42–50.

    Article  PubMed  Google Scholar 

  54. Thayu M, Leonard MB, Hyams JS, et al. Improvement in biomarkers of bone formation during infliximab therapy in pediatric Crohn’s disease: results of the REACH study. Clin Gastroenterol Hepatol. 2008;6:1378–84.

    Article  CAS  PubMed  Google Scholar 

  55. Griffin LM, Thayu M, Baldassano RN, et al. Improvements in bone density and structure during anti-TNF-alpha therapy in pediatric Crohn’s disease. J Clin Endocrinol Metab. 2015;100:2630–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Pappa HM, Langereis EJ, Grand RJ, Gordon CM. Prevalence and risk factors for hypovitaminosis D in young patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2011;53:361–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Augustine MV, Leonard MB, Thayu M, et al. Changes in vitamin D-related mineral metabolism after induction with anti-tumor necrosis factor-alpha therapy in Crohn’s disease. J Clin Endocrinol Metab. 2014;99:E991–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Long MD, Gulati A, Wohl D, Herfarth H. Immunizations in pediatric and adult patients with inflammatory bowel disease: a practical case-based approach. Inflamm Bowel Dis. 2015;21:1993–2003.

    Article  PubMed  Google Scholar 

  59. deBruyn JC, Hilsden R, Fonseca K, et al. Immunogenicity and safety of influenza vaccination in children with inflammatory bowel disease. Inflamm Bowel Dis. 2012;18:25–33.

    Article  PubMed  Google Scholar 

  60. 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;5:851–6.

    Article  PubMed  Google Scholar 

  61. deBruyn J, Fonseca K, Ghosh S, et al. Immunogenicity of influenza vaccine for patients with inflammatory bowel disease on maintenance infliximab therapy: a randomized trial. Inflamm Bowel Dis. 2016;22:638–47.

    Article  PubMed  Google Scholar 

  62. Moses J, Alkhouri N, Shannon A, et al. Hepatitis B immunity and response to booster vaccination in children with inflammatory bowel disease treated with infliximab. Am J Gastroenterol. 2012;107:133–8.

    Article  CAS  PubMed  Google Scholar 

  63. Fiorino G, Peyrin-Biroulet L, Naccarato P, et al. Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis. 2012;18:1042–7.

    Article  PubMed  Google Scholar 

  64. Dezfoli S, Horton HA, Thepyasuwan N, et al. combined immunosuppression impairs immunogenicity to tetanus and pertussis vaccination among patients with inflammatory bowel disease. Inflamm Bowel Dis. 2015;21:1754–60.

    Article  PubMed  Google Scholar 

  65. Lester R, Lu Y, Tung J. Survey of immunization practices in patients with inflammatory bowel disease among pediatric gastroenterologists. J Pediatr Gastroenterol Nutr. 2015;61:47–51.

    CAS  PubMed  Google Scholar 

  66. Mackey AC, Green L, Liang LC, Dinndorf P, Avigan M. Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007;44:265–7.

    Article  PubMed  Google Scholar 

  67. Kotlyar DS, Osterman MT, Diamond RH, et al. A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2011;9:36–41.e1.

    Article  CAS  PubMed  Google Scholar 

  68. Shale M, Kanfer E, Panaccione R, Ghosh S. Hepatosplenic T cell lymphoma in inflammatory bowel disease. Gut. 2008;57:1639–41.

    Article  PubMed  Google Scholar 

  69. 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;12:1443–51; quiz e88-9.

    Article  PubMed  Google Scholar 

  70. Hyams JS, Dubinsky MC, Baldassano RN, 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):1901–1914.e3.

    Article  PubMed  Google Scholar 

  71. Hyams JS, Wilson DC, Thomas A, et al. Natalizumab therapy for moderate to severe Crohn disease in adolescents. J Pediatr Gastroenterol Nutr. 2007;44:185–91.

    Article  CAS  PubMed  Google Scholar 

  72. Singh N, Deshpande R, Rabizadeh S, Dubinsky M. Real world experience with natalizumab at a tertiary care pediatric IBD center. J Pediatr Gastroenterol Nutr. 2016;62:863–6.

    Article  CAS  PubMed  Google Scholar 

  73. Singh N, Rabizadeh S, Jossen J, et al. Multi-center experience of vedolizumab effectiveness in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2016;22:2121–6.

    Article  PubMed  Google Scholar 

  74. Conrad MA, Stein RE, Maxwell EC, et al. Vedolizumab therapy in severe pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2016;22:2425–31.

    Article  PubMed  Google Scholar 

  75. Rinawi F, Rosenbach Y, Assa A, Shamir R. Ustekinumab for resistant pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2016;62:e34–5.

    Article  PubMed  Google Scholar 

  76. Bishop C, Simon H, Suskind D, Lee D, Wahbeh G. Ustekinumab in pediatric Crohn disease patients. J Pediatr Gastroenterol Nutr. 2016;63:348–51.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Gastroenterology, Hepatology and Nutrition, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Sonal Patel & Jennifer Strople

Authors
  1. Sonal Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer Strople
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jennifer Strople .

Editor information

Editors and Affiliations

  1. Beth Israel Deaconess Medical Center Center for Inflammatory Bowel Disease, Harvard Medical School, Boston, Massachusetts, USA

    Adam S. Cheifetz

  2. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Joseph D. Feuerstein

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Cite this chapter

Patel, S., Strople, J. (2018). Biologic Therapy in Pediatric Inflammatory Bowel Disease. In: Cheifetz, A., Feuerstein, J. (eds) Treatment of Inflammatory Bowel Disease with Biologics . Springer, Cham. https://doi.org/10.1007/978-3-319-60276-9_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-60276-9_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-60275-2

  • Online ISBN: 978-3-319-60276-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation