Biologics in Paediatric Crohn's Disease

Abstract

Crohn's disease affects increasing numbers of children worldwide. Generally, childhood-onset disease runs a more severe course than in adults and has a greater impact on quality of life. Therapy in children must take account of a different set of risks for toxicity compared to adults, but also to their longevity. Biologic drugs present remarkable advantages in terms of disease control for children, especially in those whose disease cannot be controlled with conventional therapies, but their long-term risks are still being assessed. Data regarding biologic use in children is limited and mostly amounts to case series, but results have been promising, both in terms of controlling disease activity and improving growth parameters. Adverse reactions are infrequent in the short term, but loss of response is a long-term problem, particularly in children. More information is needed about very long term risks. Infliximab and adalimumab are the most studied agents in children, while there is relatively limited data on certolizumab and natalizumab. Further collection of data on these agents is still needed, but this should not restrict access to these agents for children in whom no other agent is effective.

Altered STAT4 Isoform Expression in Patients with Inflammatory Bowel Disease

“…For established CD or UC patients, blood was drawn on their initial visit to the clinic as well as two weeks after their initial infliximab treatment. Infliximab is a recombinant chimeric immunoglobulin G monoclonal antibody that neutralizes the biologic activity of TNFα and is approved for treatment of pediatric CD and UC patients 46 . Infliximab dosage given to these pediatric patients was 5 mg/kg/dose.…”

The use of biologic agents in pediatric inflammatory bowel disease

“…Potential toxicities of anti-TNF-a treatment include infusion reactions, opportunistic infections, malignancy and rare neurological disorders [41]. Most data are extrapolated from infliximab use in adult patients and more pediatric data are essential for accurate evaluation.…”

“…However, it is difficult to establish a cause and effect relationship as IBD may carry an underlying potential risk of malignancy [41,42]. However, it is difficult to establish a cause and effect relationship as IBD may carry an underlying potential risk of malignancy [41,42].…”

Loss of Response to Long-Term Infliximab Therapy in Children with Crohn’s Disease

“…Risks in large part relate either to either allergic or infusion related reactions, the risks of infection which are probably less than those related to steroid therapy, and the potential for malignancy. The clear benefit of biologicals lie in their remarkable efficacy for many patients with otherwise treatment-resistant disease [1,2]. Remission may be maintained for long periods on this therapy, but loss of response may occur, leaving children with few other options for a lifetime of disease [3].…”

“…Recently, robust adult evidence has emerged regarding the individualization of treatment strategies by identifying the underlying pharmacological process in patients with loss of response [10]. Clinical access to biological therapies for inflammatory bowel disease in children varies internationally [2]. Unfortunately, government funding arrangements in Australia preclude strategies such as dose intensification in children [11].…”