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Top-down therapy for IBD: rationale and requisite evidence

Nature Reviews Gastroenterology & Hepatology volume 7, pages 86–92 (2010)Cite this article

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Abstract

Several trials have shown that early treatment of Crohn's disease with immunomodulators and anti-TNF agents leads to a superior clinical outcome, including healing of the mucosa, compared with standard therapy alone. Mounting evidence indicates that mucosal healing is associated with a reduced risk of complications, and a reduced need for surgeries and hospitalizations. In the SONIC trial, a combination of the standard azathioprine immunomodulator therapy and infliximab, an anti-TNF agent, had more potent anti-inflammatory effects than either drug alone in patients with Crohn's disease who had evidence of active inflammation. These findings and those from rheumatoid arthritis trials have prompted the investigation of early initiation of immunomodulator (standard or anti-TNF) therapy for Crohn's disease, in suitable patients, which has led to substantial improvements in disease management. Careful selection of patients is, however, essential given the potential risk of toxic effects from these therapies and the fact that some patients with IBD will have a favorable disease course without them. Identification of suitable patients, however, remains a challenge, as genetic, phenotypic and environmental factors have not yet been identified that can be used for routine assessment and selection is mainly based on clinical criteria.

Key Points

  • In patients with active Crohn's disease who are naive to conventional immunomodulators or biologic agents, combination therapy induces better rates of clinical and endoscopic remission than monotherapy

  • Patients with Crohn's disease usually have a better response to biologic therapy when treatment is initiated earlier in the disease course

  • Clinical parameters can be used to predict an unfavorable disease course in Crohn's disease and thus to identify patients who should be treated more aggressively early on

  • As potent and combined immunosupression is possibly associated with more toxic effects than standard therapy, the benefit of aggressive treatment needs to be balanced against potentially severe adverse events

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  1. Imelda GI Clinical Research Center, Imeldalaan 9, Bonheiden, 2820, Belgium

    Geert R. D'Haens

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The author has acted as a consultant, received honoraria for lectures and received research support from the following companies: Centocor BV, Schering Plough, Abbott and UCB.

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D'Haens, G. Top-down therapy for IBD: rationale and requisite evidence. Nat Rev Gastroenterol Hepatol 7, 86–92 (2010). https://doi.org/10.1038/nrgastro.2009.222

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