The safety of treatment options for pediatric Crohn’s disease

ABSTRACT

Introduction: A severe clinical phenotype along with concern for ensuring normal growth and development has a major impact on treatment choices for children newly diagnosed with Crohn’s disease (CD).

Areas covered: We review the increasingly outdated concept of ‘conventional’ therapy of pediatric CD based on aminosalicylates, corticosteroids, and immunomodulators for patients at high risk of complicated disease. Key safety concerns with each treatment are reviewed.

Expert opinion: There are minimal data supporting the use of aminosalicylates in the treatment of pediatric CD. Corticosteroids are effective short-term for improving signs and symptoms of disease but are ineffective for maintenance therapy. Thiopurines decrease corticosteroid dependence but may not alter progression to complicated disease requiring surgery. Concerns for lymphoma as well as hemophagocytic lymphohistiocytosis with thiopurines are valid. Further data are required on the efficacy and safety of methotrexate as an alternative immunomodulator. Though generally well tolerated and efficacious in most patients, anti-TNF-α therapy can be associated with both mild as well as more serious complications. Current data do not support an increased risk for malignancy associated with anti-TNF therapy alone in children. Anti-adhesion therapy appears to have a favorable safety profile but the experience in children is extremely limited.

KEYWORDS:

• Thiopurines
• infliximab
• Crohn’s
• children

Article highlights

• Treatment of inflammatory bowel disease in children increasingly includes early exposure to immunomodulators and biologics

• Concern about malignancy risk with thiopurines is limiting their use and prompting increased utilization of methotrexate as an alternative immunomodulator

• Anti-TNFα therapy while effective in most cases of moderate to severe disease can be associated with complications including infusion reactions, neutropenia, psoriasis, and less commonly infection and autoimmunity.

• Concomitant thiopurine and anti-TNFα exposure may be the most significant risk for the development of hepatosplenic T-cell lymphoma

• Anti-integrin therapy appears to have a favorable safety profile but data in children are extremely limited

This box summarizes key points contained in the article.

Declaration of interest

J Hyams has acted as consultant, participated on advisory board and received research support from Janssen Biotech, participated on advisory board and received research support from Abbvie, participated on advisory board and acted as consultant for Takeda. He has also acted as consultant for Soligenix, UCB, Celgene, Lilly, Receptos and Boehringer Ingelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.