Andrew S. Day, Ajay S. Gulati, Nishaben Patel, Brendan Boyle, K.T. Park, Shehzad A. Saeed

The treatment goal for children suffering from inflammatory bowel disease (IBD) has been evolving with biologic therapies like anti-TNF agents assuming a more central role in treatment of more aggressive and extensive phenotype. Earlier introduction of anti-TNF agents have shown to be more effective and may even alter the natural history of IBD. However, development of anti-drug antibodies (ADA) limits long term usage and leads to dose adjustment in almost half of patients treated with these medications. One of the strategies to minimize the development of ADA has been concomitant use of immunomodulator (IM) medications, resulting in fewer infusion reactions and sustained trough levels, potentially lowering the need for dose adjustments. However, balanced with these benefits of optimized dosing and likely more sustained response, is the concern about increased risk of complications, such as infections and malignancies. The current manuscript reviews the available pediatric literature regarding efficacy, safety and side effect profile of combination (IM and biologics) therapy in pediatric Crohn's disease and ulcerative colitis, with particular emphasis on cost constraints, and recommendations for selection of patients who would benefit most from combination therapy.