An overview of a presentation by Associate Professor Marla Dubinsky from Cedars-Sinai Medical Center, USA, at the Raising Expectations in Gastroenterology symposium, 2012.

Onset of Crohn's disease in childhood can often lead to complex illness with poor outcomes. Decisions about treatment of children with Crohn's disease require careful assessment of the risks of the disease itself and the risks of treatment. It is important to clearly communicate the risks and benefits of therapy to patients and their families to facilitate decision-making.

"Patients and their parents are willing to accept higher risks of adverse events for greater anticipated benefit"

Thiopurines

Crohn's disease improves maintenance of remission and reduces cumulative steroid dose.1 However, stratifying risk to identify which patients would gain most from 6-MP and steroid-sparing would be helpful because about 50% of patients achieve remission without 6-MP.1

Use of thiopurines can be optimised by monitoring metabolite and thiopurine methyltransferase (TPMT) enzyme levels to achieve therapeutic dosing levels.2 However, if patients remain unwell after 3 months despite therapeutic drug levels, patients may be switched to a biologic therapy.

Infliximab

Infliximab is effective for the induction and maintenance of remission in children with moderate to severe Crohn's disease.3 An induction regimen of infliximab 5 mg/kg administered at weeks 0, 2 and 6 was associated with:3

  • 88.4% response rate at week 10 (reduction of ≥15 points in the Paediatric Crohn’s Disease Activity Index [PCDAI])
  • 58.9% clinical remission (PCDAI <10 points)
  • Improved height status

Risks associated with treatment

Steroids are the cornerstone of therapy in children with Crohn's disease, but they can be associated with serious adverse effects including opportunistic infection and growth retardation.4–6

Biologic therapies have been associated with an increased risk of infection, infusion reactions and malignancy:6

  • Non-Hodgkin's lymphoma (NHL): Risk of NHL is increased in patients receiving anti-TNF therapy compared with the general population (OR 3.2, 95% CI: 1.5–6.9), but it is unclear whether the risk is attributable to anti-TNF therapy, thiopurines or the combination of both7
  • Hepatosplenic T-cell lymphoma (HSTCL): In a review of 36 cases of HSTCL, the majority of cases occurred in males, patients aged <35 years, and patients receiving thiopurine plus anti-TNF or thiopurine monotherapy (no cases occurred in patients receiving anti-TNF monotherapy)8

Summary

  • Onset in childhood can often lead to complex illness with poor outcome
  • Decisions about treatment of children with Crohn's disease require careful assessment of the risks of the disease itself and the risks of treatment
  • Thiopurines and infliximab have demonstrated efficacy in children with Crohn's disease
  • Risks associated with therapy include increased risk of infection, growth retardation (steroids), malignancy and infusion reactions (biologics)

Please note, the views expressed in this article are not necessarily those of the sponsor.

References

  1. Markowitz J et al. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease. Gastroenterology 2000; 119: 895–902.
  2. Seidman EG. Clinical use and practical application of TPMT enzyme and 6-mercaptopurine metabolite monitoring in IBD. Reviews in Gastroenterological Disorders 2003; 3 Suppl 1: s30–s38.
  3. Hyams J et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology 2007; 132: 863–873.
  4. Toruner M et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008; 134: 929–936.
  5. Lichtenstein GR et al. Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. Clinical Gastroenterology and Hepatology 2006; 4: 621–630.
  6. Fell JME. Update of the management of inflammatory bowel disease. Archives of Disease in Childhood 2012; 97: 78–83.
  7. Kotlyar DS et al. A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Clinical Gastroenterology and Hepatology 2011; 9: 36–41.
  8. Van Assche G et al. The London position statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: safety. American Journal of Gastroenterology 2011; 106: 1594–1602.

PBS information: This product is listed as a Section 100 item for Crohn’s disease and ulcerative colitis. Refer to PBS Schedule for full authority information.

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