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Future biologic targets for IBD: potentials and pitfalls

Nature Reviews Gastroenterology & Hepatology volume 7, pages 110–117 (2010)Cite this article

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Abstract

The treatment of patients with IBD has evolved towards biologic therapy, which seeks to target specific immune and biochemical abnormalities at the molecular and cellular level. Multiple genes have been associated with susceptibility to IBD, and many of these can be linked to alterations in immune pathways. These immune pathways provide avenues for understanding the pathogenesis of IBD and suggest future drug targets, such as the IL-12–IL-23 pathway. In addition, failed therapeutic drug trials can provide valuable information about pitfalls in study design, drug delivery and disease activity assessment. Future biologic drug development will benefit from the early identification of subsets of patients who are most likely to respond to therapy by use of biological markers of genetic susceptibility or immunologic susceptibility.

Key Points

  • Multiple genetic associations with IBD have been discovered in the past few years

  • Several susceptibility genes are associated with innate or adaptive immune system pathways and these pathways provide multiple targets for therapeutic intervention

  • Potential pitfalls in future biologic drug development relate to historically high placebo response rates in patients with IBD

  • Biological markers of disease activity, genetic susceptibility and immunologic susceptibility may significantly increase drug response rates relative to placebo

  • Future drug development should focus on subpopulations of patients with specific genetic and immunologic profiles who stand to benefit the most from targeted therapy

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Figure 1: Therapeutic targets for IBD.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, 8635 West 3rd Street, 960-W, Los Angeles, 90048, CA, USA

    Gil Y. Melmed & Stephan R. Targan

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  1. Gil Y. Melmed
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Correspondence to Gil Y. Melmed.

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Competing interests

G. Y. Melmed is on the speaker's bureau for Abbot, Proctor & Gamble, and Shire. He is also a Consultant for Amgen and UCB. S. R. Targan is a Consultant for Amgen, Elan, Proctor & Gamble, Prometheus, and Wyeth. He is also on the Board of Directors for Prometheus.

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Supplementary Table 1

The IBD biologic pipeline. (DOC 121 kb)

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Melmed, G., Targan, S. Future biologic targets for IBD: potentials and pitfalls. Nat Rev Gastroenterol Hepatol 7, 110–117 (2010). https://doi.org/10.1038/nrgastro.2009.218

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