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Phenotypic Features of Crohn's Disease Associated With Failure of Medical Treatment

  • Gordon W. Moran
    Affiliations
    Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada

    Division of Gastroenterology, University of Calgary, Alberta, Canada

    Department of Medicine, University of Calgary, Alberta, Canada

    Nottingham Digestive Diseases Centre, Biomedical Research Unit, University of Nottingham, Nottingham, United Kingdom
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  • Marie–France Dubeau
    Affiliations
    Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada

    Division of Gastroenterology, University of Calgary, Alberta, Canada

    Department of Medicine, University of Calgary, Alberta, Canada
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  • Gilaad G. Kaplan
    Affiliations
    Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada

    Division of Gastroenterology, University of Calgary, Alberta, Canada

    Department of Medicine, University of Calgary, Alberta, Canada

    Department of Community Health Sciences, University of Calgary, Alberta, Canada
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  • Hong Yang
    Affiliations
    Department of Community Health Sciences, University of Calgary, Alberta, Canada
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  • Cynthia H. Seow
    Affiliations
    Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada

    Division of Gastroenterology, University of Calgary, Alberta, Canada

    Department of Medicine, University of Calgary, Alberta, Canada
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  • Richard N. Fedorak
    Affiliations
    Division of Gastroenterology, Department of Medicine University of Alberta, Edmonton, Alberta, Canada
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  • Levinus A. Dieleman
    Affiliations
    Division of Gastroenterology, Department of Medicine University of Alberta, Edmonton, Alberta, Canada
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  • Herman W. Barkema
    Affiliations
    Department of Community Health Sciences, University of Calgary, Alberta, Canada

    Department of Production Animal Health, University of Calgary, Alberta, Canada
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  • Subrata Ghosh
    Affiliations
    Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada

    Division of Gastroenterology, University of Calgary, Alberta, Canada

    Department of Medicine, University of Calgary, Alberta, Canada
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  • Remo Panaccione
    Correspondence
    Reprint requests Address requests for reprints to: Remo Panaccione, MD, FRCPC, Teaching Research and Wellness Center, 3280 Hospital Drive NW, 6D30, Calgary, Alberta T2N 4N1, Canada; fax: (403) 270-7287.
    Affiliations
    Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada

    Division of Gastroenterology, University of Calgary, Alberta, Canada

    Department of Medicine, University of Calgary, Alberta, Canada
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  • on Behalf of theAlberta Inflammatory Bowel Disease Consortium
Published:August 26, 2013DOI:https://doi.org/10.1016/j.cgh.2013.08.026

      Background & Aims

      There is conflicting evidence on the effects of thiopurines (azathioprine or mercaptopurine) and anti–tumor necrosis factor (TNF) therapies on rates of surgery among patients with Crohn's disease (CD). We aimed to identify factors that identify patients who are unlikely to respond to medical therapy and will therefore require surgery.

      Methods

      We performed a retrospective study using the Alberta Inflammatory Bowel Disease Consortium registry to identify 425 patients diagnosed with CD who received a prescription of a thiopurine and/or an anti-TNF agent from a referral center, from July 1, 1975, through September 13, 2012. We collected data on CD-related abdominal surgery after therapy and disease features when therapy was instituted. Cox proportional regression models were used to associate disease features with outcomes after adjusting for potential confounders. Risk estimates were presented as hazard rate ratios (HRRs) with 95% confidence intervals (CIs).

      Results

      Among patients given thiopurines, stricturing disease (adjusted HR, 4.63; 95% CI, 2.00–10.71), ileal location (adjusted HR, 6.20; 95% CI, 1.64–23.42), and ileocolonic location (adjusted HR, 3.71; 95% CI, 1.08–12.74) at the time of prescription were associated significantly with the need for surgery. Prescription of an anti-TNF agent after prescription of a thiopurine reduced the risk for surgery, compared with patients prescribed only a thiopurine (adjusted HR, 0.41; 95% CI, 0.22–0.75). Among patients given anti-TNF agents, stricturing (adjusted HR, 6.17; 95% CI, 2.81–13.54) and penetrating disease (adjusted HR, 3.39; 95% CI, 1.45–7.92) at the time of prescription were associated significantly with surgery. Older age at diagnosis (17–40 y) reduced the risk for abdominal surgery (adjusted HR, 0.41; 95% CI, 0.21–0.80) compared with a younger age group (≤16 y). Surgery before drug prescription reduced the risk for further surgeries among patients who received thiopurines (adjusted HR, 0.33; 95% CI, 0.13–0.68) or anti-TNF agents (adjusted HR, 0.49; 95% CI, 0.25–0.96). Terminal ileal disease location was not associated with a stricturing phenotype.

      Conclusions

      Based on a retrospective database analysis, patients prescribed thiopurine or anti-TNF therapy when they have a complicated stage of CD are more likely to require surgery. Better patient outcomes are achieved by treating CD at early inflammation stages; delayed treatment increases rates of treatment failure.

      Keywords

      Abbreviations used in this paper:

      Anti-TNF (anti–tumor necrosis factor), CD (Crohn's disease), CI (confidence interval), HRR (hazard rate ratio)
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