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Early Use of Thiopurines or Methotrexate Reduces Major Abdominal and Perianal Surgery in Crohn's Disease

Kariyawasam, Viraj C. MBBS, MRCP, FRACP*,†; Selinger, Christian P. MD, MSc, MRCP*,‡; Katelaris, Peter H. MBBS, FRACP, FRCP, MD*,†; Jones, D. Brian MBBS, FRACP, FRCP*,†; McDonald, Charles MBBS, FRACP*; Barr, Gavin MBBS, FRACP*; Chapman, Grace MBBS, FRACP*; Colliwshaw, James MBBS, FRACP*; Lunney, Paul C. RN*,†; Middleton, Kate BMedSc, MBBS*,†; Wang, Rosy R. BSc*,†; Huang, Tony*,§; Andrews, Jane MBBS, FRACP, PhD; Leong, Rupert W. MBBS, FRACP, MD*,§

doi: 10.1097/MIB.0000000000000119
Original Clinical Articles

Background: Earlier introduction of immunomodulators (IM) thiopurine or methotrexate is advocated to improve Crohn's disease (CD) outcomes, but whether abdominal surgery can be prevented remains controversial.

Methods: A specialist-referred cohort of CD was recruited from 1970 to 2009. Early IM use was defined as commencement of azathioprine or methotrexate within 3 years of CD diagnosis and adherence of at least 6 months. Propensity score matching was conducted to correct for confounders influencing early IM introduction. Outcomes of interest were rates of initial and recurrent major abdominal surgery for CD and their predictive factors.

Results: A total of 1035 consecutive patients with CD (13,061 patient-years) were recruited. The risk of first and recurrent major abdominal surgery at 1, 5, and 10 years were 17.5%, 28.4%, and 39.5% and 5.9%, 19.0%, and 33.3%, respectively. Early IM use increased over time from 1.3% to 55.3% (P < 0.0001) and was a significant independent predictor of lower rates of initial abdominal surgery (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.35–0.69), recurrent abdominal surgery (HR, 0.44; 95% CI, 0.25–0.79) and perianal surgery (HR, 0.30; 95% CI, 0.16–0.56). Using propensity score matching, early IM significantly reduced surgical rates (HR, 0.54; 95% CI, 0.37–0.79). Number needed to treat to prevent a surgical event at 5 years from diagnosis and after initial surgery was 6.99 (95% CI, 5.34–11.95) and 8.59 (95% CI, 6.26–23.93), respectively.

Conclusions: Early IM use with thiopurines or methotrexate was significantly associated with the reduced need for abdominal and perianal surgery in CD.

Article first published online 2 July 2014.Supplemental Digital Content is Available in the Text.

*Gastroenterology and Liver Services, Concord Hospital, Sydney, Australia;

Faculty of Medicine, University of Sydney, Sydney, Australia;

Leads Teaching Hospitals NHS Trust, Leeds, United Kingdom;

§Faculty of Medicine, The University of New South Wales, Sydney, Australia; and

IBD Services, Department of Gastroenterology, Royal Adelaide Hospital, Adelaide, Australia.

Reprints: Viraj C. Kariyawasam, MBBS, Department of Gastroenterology, Concord Hospital, Hospital Road, Concord, NSW, Australia 2139 (e-mail:

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

C. P. Selinger has received grants from Ferring, Shire, Warner Chillcott, and Nycomed. J. Andrews is on the advisory boards for Janssen, AbbVie, Ferring, Nycomed, Abbott and have also received research support. Consulted for Shure, Fresenius Kabi, VitalFoods, Orphan. Received speaker fees from all of the previous companies, including AstraZeneca. R. W. Leong is part-funded by a National Health and Medical Research Council Career Development Fellowship and is on the advisory board of Ferring Pharmaceuticals, AbbVie Australia, Janssen, Takeda and has received honoraria from Ferring Pharmaceuticals, AbbVie Australia, Janssen, Shire. The other authors have no conflicts of interest to disclose.

Received April 21, 2014

Accepted May 16, 2014

© Crohn's & Colitis Foundation of America, Inc.
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