Personalizing therapy for inflammatory bowel diseases

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Date: Aug. 2013
Publisher: Expert Reviews Ltd.
Document Type: Report
Length: 9,132 words
Lexile Measure: 1490L

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Author(s): Ashwin N Ananthakrishnan [*] 1

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biologics; Crohn's disease; genetics; serology; ulcerative colitis

Inflammatory bowel diseases (IBDs) affect an estimated 1.7 million Americans and 2.2 million people in Europe [1-3] . In addition, there is a rising incidence of IBD in parts of the world where they were previously considered uncommon [4] . Annual IBD-related healthcare costs in the USA are estimated to be nearly US$6 billion [5] . The burden of these illnesses is further extended by their onset during adolescence or young adulthood and protracted course characterized by relapses through much of the economically productive years. Despite significant advances in therapy that have enhanced our ability to achieve disease remission, the costs of such treatments remain considerable precluding widespread adoption. In addition, safety concerns of such therapies remain. Personalizing therapy for IBD rests on two premises. First, that we can predict which patients are likely to have aggressive disease, and second, that early therapy in such patients prevents disease progression, related complications and maintains bowel function. This review attempts to summarize the existing literature that addresses the above two questions, identify gaps in research, and suggest potential areas for exploration in future studies.

Need for personalizing therapy: changing therapeutic paradigms

The need for personalizing IBD therapy is highlighted by several recent studies suggesting the need to modify the conventional paradigms in the management of these chronic and progressive diseases. First, patients respond better when effective therapies are instituted early on in the course of disease. The landmark step-up/top-down trial randomized patients with Crohn's disease (CD) to either the traditional step-up approach with introduction of azathioprine (AZA) after failure of two courses of steroids, or to early induction doses of infliximab followed by AZA maintenance [6] . Despite similar clinical response 2 years after treatment, patients treated with infliximab early on were more likely to have absence of mucosal ulceration at year 2 despite comparable rates of AZA and infliximab use at the end of the study. Second, another landmark study, the SONIC trial, demonstrated a superior efficacy with use of combination immunosuppressive therapy with AZA and infliximab when compared with either agent alone in early CD [7] . Third, there has been recognition that resolution of clinical symptoms alone is insufficient to prevent progression of disease. Patients who are able to achieve mucosal healing have a lower likelihood of requiring surgery and a reduced incidence of colorectal neoplasia [8-11] . Indeed, such an approach may be more cost-effective than treating to clinical remission [8] . Nevertheless, the optimal definition of mucosal healing remains uncertain and whether all patients would achieve equal incremental benefit from escalating therapy to achieve complete absence of mucosal inflammation and resolution of histologic inflammation is unclear. Finally, agents acting through other inflammatory- or immune-targets are available or likely to be approved for use soon including natalizumab, vedolizumab and ustekinumab [12] . The spectrum of inflammatory mechanisms that can be targeted suggest that we may be able to use specific therapies in individuals based on their individual likelihood of response to such a...

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Gale Document Number: GALE|A341859529