SEVERE PANCOLITIS: A RARE ADVERSE EFFECT OF NINTEDANIB

Abstract

SESSION TITLE: Diffuse Lung Disease SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 pm - 02:15 pm INTRODUCTION: Nintedanib is a tyrosine kinase receptor blocker that inhibits multiple fibrogenic growth factors. It is one of the only two currently available drugs that have been shown to slow the decline in lung function in patients with idiopathic pulmonary fibrosis (IPF). While some gastrointestinal adverse effects are common in patients taking nintedanib, severe pancolitis has only been reported once before [1]. CASE PRESENTATION: Our patient is a 61-year-old Caucasian gentleman who was diagnosed with IPF based clinico-radiologic and surgical lung biopsy findings. He was started on nintedanib and tolerated 150 mg twice a day dose well. While on therapy his pulmonary function tests remained fairly stable. 1.5 years after having been on nintedanib he developed severe diarrhea. Nintedanib was discontinued however his diarrhea did not improve. He underwent colonoscopy that revealed pancolitis. Colonic biopsies showed severe active inflammation with frequent crypt abscess formation. Dense basal lymphoplasmocytic infiltrates were not seen, therefore, making ulcerative colitis less likely. Rather, drug induced colitis caused by nintedanib was considered. Patient was treated with prednisone with rapid resolution of symptoms. At this point, patient was rechallenged with nintedanib. He tolerated low dose therapy, but as soon as the dose was increased back to 150 mg twice a day, the symptoms recurred. This further confirmed his colitis as being drug induced. Nintedanib has since been discontinued and the patient has been switched to pirfenidone, which he has been tolerating well. DISCUSSION: In nintedanib’s clinical trials up to 62% of the patients experienced diarrhea. However, it was mostly mild to moderate in intensity. Diarrhea led to discontinuation of therapy in less than 5% of the cases. Our case is unique for two reasons. Firstly, our patient had severe pancolitis seen on colonoscopy and further confirmed by histopathology. Inflammatory bowel disease (IBD) and infections were adequately excluded. There has been only one prior published report of nintedanib induced severe pancolitis that was confirmed histopathologically. Secondly, our patient tolerated nintedanib well for 1.5 years before the onset of symptoms. Most of the times diarrhea is seen with in the first few weeks of initiation of therapy. Nintedanib slows down pulmonary fibrosis by inhibiting fibroblast growth factor, vascular endothelial growth factor and platelet derives growth factor. Unfortunately, these mediators are also involved in angiogenesis and repair of gastrointestinal tract. Therefore, their inhibition by nintedanib predisposes patients to adverse effects like colitis. CONCLUSIONS: Nintedanib can rarely cause severe pancolitis, even several months after initiation of therapy. After excluding alterative etiologies, nintedanib induced pancolitis can be treated with drug discontinuation and steroids. Reference #1: Oda K, Matsunaga T, Sennari K, Yatera K. Colitis Associated with Nintedanib Therapy for Idiopathic Pulmonary Fibrosis (IPF). Intern Med 2017;56(10):1267–1268. DISCLOSURES: No relevant relationships by Muhammad Ali, source=Web Response No relevant relationships by Mark Barash, source=Web Response No relevant relationships by Aasim Mohammed, source=Web Response Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim pharmaceuticals Please note: $5001 - $20000 Added 03/03/2018 by Vijay Ramalingam, source=Web Response, value=HonorariaRemoved 03/03/2018 by Vijay Ramalingam, source=Web Response Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim pharmaceuticals Please note: $1001 - $5000 Added 03/03/2018 by Vijay Ramalingam, source=Web Response, value=Honoraria