Colopathy Associated with Pentosan Polysulfate Use

Emily H Jung¹Wei Zheng²Ryan J Weiss³Namita E Mathew²Benjamin I Meyer⁴Azhar Nizam⁵Heba Iskandar²Nieraj Jain^2*

• ¹School of Medicine, Duke University, Durham, North Carolina, United States
• ²School of Medicine, Emory University, Atlanta, Georgia, United States
• ³University of Georgia, Athens, Georgia, United States
• ⁴Bascom Palmer Eye Institute, University of Miami Health System, Miami, Florida, United States
• ⁵Department of Biomedical Informatics, School of Medicine, Emory University, Atlanta, Georgia, United States

We describe a novel colopathy associated with pentosan polysulfate (PPS) use and assess the strength of the drug-disease association in a two-part investigation.We studied individuals with a history of long-term PPS use. Case histories concerning gastrointestinal disease were obtained through review of endoscopy records and histopathology specimens. Findings were summarized with descriptive statistics.2. Cross-Sectional Study: We evaluated patients with interstitial cystitis at a single clinical center. We obtained data on drug exposure and medical histories and measured the strength of association between PPS use and diagnoses of inflammatory bowel disease (IBD) using multivariate logistic regression.1. Cohort Study: Among 13 participants, the median PPS exposure was 2.04 kg (range 0.99-2.54 kg).Eleven participants (84.6%) developed IBD symptomatology after initiating PPS therapy, and 9 (69.2%) were diagnosed with IBD. Two others (18%) were diagnosed with irritable bowel syndrome.Of the 10 participants with endoscopic and histopathologic data, six had abnormal colonic mucosa on endoscopy, and all 10 had histologic abnormalities. Clinical and histologic improvement was noted after PPS cessation, though two (18%) required colectomy for colitis-associated dysplasia.2. Cross-Sectional Study: Among 219 subjects with interstitial cystitis, PPS use was a statistically significant predictor of an IBD diagnosis, with an adjusted odds ratio of 3.3 (95% confidence interval, 1.2-8.8, p=0.02).Our study identifies a strong association between PPS use and clinical diagnosis of IBD. Histopathologic findings suggest a novel drug-associated colopathy, with some subjects necessitating colectomy for dysplasia.Further investigation into the causality of this association is warranted.