ISCHEMIC COLITIS WITH NINTEDANIB USE: THE CONUNDRUM OF A COMMON SYMPTOM DUE TO A RARE CAUSE

Abstract

SESSION TITLE: Fellows Diffuse Lung Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Most common adverse effects of Nintedanib are nausea, diarrhea, and liver dysfunction. Serious adverse events have been reported in approximately 30% of patients receiving Nintedanib treatment. We report a case of Nintedanib induced ischemic colitis in a patient with idiopathic pulmonary fibrosis. CASE PRESENTATION: An 84-year-old Caucasian Male with a past medical history significant for IPF presented to the Emergency Department with progressively worsening diffuse abdominal pain, anorexia, and diarrhea. He started taking Nintedanib 7 days before. Abdominal exam revealed rebound tenderness with guarding and rigidity. Laboratory evaluation showed an elevated leukocyte count and a normal lactate. Computed tomography scan of the abdomen demonstrated inflammatory changes and mildly dilated small bowel loops without any signs of obstruction. He underwent an urgent diagnostic laparoscopy for further evaluation. Procedure was converted to a laparotomy after he was noted to have ischemic bowel, with resection of the terminal ileum, cecum, and appendix. Pathology of resected specimen showed transmural ischemic necrosis of terminal ileum and cecum. Nintedanib was discontinued and he was discharged home in stable condition after an uneventful post-operative course. DISCUSSION: Nintedanib is a tyrosine kinase inhibitor that mediate elaboration of fibrogenic growth factors (eg, platelet-derived growth factor, vascular endothelial growth factor - VEGF, fibroblast growth factor). Nintedanib and its byproducts may cause direct intestinal mucosal damage. VEGF mediates release of nitric oxide, and its inhibition causes vasoconstriction. VEGFR inhibition significantly reduces the capillary network in intestinal villi. The WHO pharmaceutical newsletter showed disproportional reporting of colitis with Nintedanib use. Authors identified 10 cases of possible colitis from around the world. Pathology results were available in only 3/10 patients. Diarrhea and GI perforation are listed on Nintedanib’s prescribing label, while ischemic bowel (colitis) is not listed as an adverse event. CONCLUSIONS: Ischemic colitis can be a life-threatening condition if not detected early. It is important for health care providers to be aware of this complication when patients on Nintedanib who develop diarrhea, in the context of other abdominal complaints and findings. Reference #1: Kato M, Sasaki S, Nakamura T, et al. Gastrointestinal adverse effects of nintedanib and the associated risk factors in patients with idiopathic pulmonary fibrosis. Sci Rep. 2019;9(1):12062. Published 2019 Aug 19. doi:10.1038/s41598-019-48593-4 Reference #2: Takahashi S, Murata S, Yoshino Y, Kobayashi Y, Nakamura M. Gastric perforation related to concurrent use of nintedanib and ramucirumab. Respirol Case Rep. 2018;7(1):e00383. Published 2018 Nov 8. doi:10.1002/rcr2.383, Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008;8(8):579-91. Kamba T, Tam BY, Hashizume H, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006;290(2):H560-76. Reference #3: Liu J, Nicum S, Reichardt P, Croitoru K, et al. Assessment and management of diarrhea following VEGF receptor TKI treatment in patients with ovarian cancer. Gynecol Oncol. 2018;150(1):173-179. 6) https://apps.who.int/iris/bitstream/handle/10665/330444/WPN-2019-06-eng.pdf?ua=1 (accessed 3/13/2020) 7) https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf (accessed 3/13/2020) https://apps.who.int/iris/bitstream/handle/10665/330444/WPN-2019-06-eng.pdf?ua=1 (accessed 3/13/2020) https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf (accessed 3/13/2020) DISCLOSURES: Consultant relationship with Veracyte Please note: $1001 - $5000 Added 04/03/2020 by Steven Nathan, source=Web Response, value=Honoraria Consultant relationship with United Therapeutics Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Consulting fee Consultant relationship with Bellerophon Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Roche-Genentech Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boerhinger-Ingelheim Please note: $20001 - $100000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Honoraria Consultant relationship with Boehringer Ingelheim Pharmaceuticals Please note: $1001 - $5000 Added 05/18/2020 by Vijay Ramalingam, source=Web Response, value=Honoraria No relevant relationships by Anusha Yelisetty, source=Web Response