Colopathy Associated with Pentosan Polysulfate Use

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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement RJW is funded by the University of Georgia Startup Funds. NJ is funded by the Foundation Fighting Blindness Career Development Award CD-C-0918-0748-EEC and the National Eye Institute P30EY006360 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of Emory University gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript.