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[Preprint]. 2023 Apr 4:2023.04.03.23288071. [Version 1] doi: 10.1101/2023.04.03.23288071

Colopathy Associated with Pentosan Polysulfate Use

Emily H Jung, Wei Zheng, Ryan J Weiss, Namita E Mathew, Benjamin I Meyer, Azhar Nizam, Heba Iskandar, Nieraj Jain
PMCID: PMC10104206  PMID: 37066211

Abstract

Introduction

We describe a novel colopathy associated with pentosan polysulfate (PPS) use and measure the strength of the drug-disease association.

Methods

Two-part investigation. In the cohort study of individuals with a history of prior long-term PPS use, case histories were obtained and gastrointestinal disease course was followed with review of endoscopy records and histopathology specimens. Findings were summarized with descriptive statistics. In the cross-sectional study of individuals with interstitial cystitis, drug exposure and medical histories were obtained for patients seen at a single clinical center. Strength of association between PPS use and diagnoses of inflammatory bowel disease (IBD) and/or irritable bowel syndrome (IBS) was measured with multivariate logistic regression.

Results

In the cohort study of 13 participants, median PPS exposure was 2.04 kg (0.99–2.54). Eleven (84.6%) developed symptoms suggestive of IBD and/or IBS after initiation of PPS therapy. Of the 10 participants whose endoscopic and histopathologic findings we reviewed, six had abnormal-appearing colonic mucosa on endoscopy and all 10 had abnormal mucosal changes on histology. Clinical and histologic improvement was observed after PPS cessation. In the cross-sectional study of 219 subjects with interstitial cystitis, PPS use was a statistically significant predictor of both the IBD [adjusted odds ratio=3.3 (95% confidence interval, 1.2–8.8, p=0.02)] and the composite IBD+IBS [adjusted odds ratio=3.3 (95% confidence interval, 1.5–7.3, p=0.002)] outcomes.

Discussion

We describe a strong association between PPS use and a clinical diagnosis of IBD and/or IBS. Histopathologic findings suggest a novel drug-associated colopathy, with some subjects requiring colectomy for dysplasia.

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The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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