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The association between pre-colectomy thiopurine use and risk of neoplasia after ileal pouch anal anastomosis in patients with ulcerative colitis or indeterminate colitis: a propensity score analysis

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Abstract

Background

The risk of neoplasia of the pouch or residual rectum in patients with ulcerative colitis (UC) who undergo total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is incompletely investigated. Thiopurine use is associated with a reduced risk of colorectal neoplasia in patients with UC. We tested the hypothesis that thiopurine use prior to TPC may be associated with a reduced risk of primary neoplasia after IPAA.

Methods

We conducted a retrospective cohort analysis of patients from a tertiary referral center from January 2008 to December 2017. Eligible patients with UC or IC underwent TPC with IPAA and had at least two pouchoscopies with biopsies ≥ 6 months after surgery. Propensity score analysis was conducted to match thiopurine exposed vs unexposed groups based on clinical covariates. Multivariable Cox regression analysis estimated the risk of neoplasia.

Results

A total of 284 patients with UC or IC (57.4% male, median age 35.6 years) were analyzed. Ninety-seven patients (34.2%) were confirmed to have thiopurine exposure ≥ 12 weeks immediately prior to TPC (“exposed”) and 187 (65.8%) were confirmed to have no thiopurine exposure for at least 365 days prior to TPC (“non-exposed”). Compared to non-exposed patients, patients with thiopurine exposure less often had dysplasia (7.2% vs 23.0%, p = 0.001) and had lower grades of dysplasia before colectomy. After IPAA, patients with neoplasia were older (44.0 vs 34.8 years, p = 0.03), more likely to have had dysplasia as colectomy indication (44.4% vs 15.4%, p = 0.007), and more likely to require pouch excision (55.6% vs 10.2%, p < 0.0001), compared to patients without neoplasia. On propensity-matched cohort analysis, no factors were significantly associated with risk of primary neoplasia.

Conclusion

Thiopurine exposure for at least the 12 weeks prior to TPC in patients with UC or IC does not appear to be independently associated with risk of primary neoplasia following IPAA.

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Funding

SCS is supported by the American Gastroenterological Association Research Scholar Award and Veterans Affairs Career Development Award under award number ICX002027A.

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Authors and Affiliations

  1. Department of Medicine, Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1069, New York, NY, USA

    Maia Kayal, Alexa Riggs & Steven H. Itzkowitz

  2. Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Michael Plietz, Sergey Khaitov, Patricia Sylla & Alexander J. Greenstein

  3. Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Noam Harpaz

  4. Department of Medicine, Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN, USA

    Shailja C. Shah

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  1. Maia Kayal
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Contributions

Guarantor of the article: Maia Kayal is the submission’s guarantor and takes responsibility for the integrity of the work as a whole, from inception to the publication of the article. MK: study concept and design, acquisition of data, statistical analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content; AR: critical revision of the manuscript for important intellectual content, statistical analysis; MP: acquisition of data, critical revision of the manuscript for important intellectual content; SK: critical revision of the manuscript for important intellectual content; PS: critical revision of the manuscript for important intellectual content; AJG: critical revision of the manuscript for important intellectual content; NH: critical revision of the manuscript for important intellectual content; SHI: critical revision of the manuscript for important intellectual content; SCS: study concept and design, statistical analysis and interpretation of data, critical revision of the manuscript for important intellectual content. All authors approved the final version of the manuscript.

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Correspondence to Maia Kayal.

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Kayal, M., Riggs, A., Plietz, M. et al. The association between pre-colectomy thiopurine use and risk of neoplasia after ileal pouch anal anastomosis in patients with ulcerative colitis or indeterminate colitis: a propensity score analysis. Int J Colorectal Dis 37, 123–130 (2022). https://doi.org/10.1007/s00384-021-04033-2

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