AUTOIMMUNITY TRIGGERED BY IMMUNOTHERAPY: A CASE OF AUTOIMMUNE HEPATITIS-INDUCED BY NINTEDANIB TREATMENT FOR IPF

Abstract

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by progressive loss of lung function, dyspnea and impairment in quality of life.1 Nintedanib is a tyrosine kinase inhibitor approved for treatment of IPF which can reduce the annual rate of decline in forced vital capacity.2 Nintedanib’s adverse effects are managed symptomatically, by dose reduction or treatment interruption.3 We present a case of drug induced autoimmune hepatitis associated with Nintedanib. CASE PRESENTATION: A 59-year-old male with 19 pack year smoking history, COPD GOLD group B, GERD and CAD who initially presented to his PCP 2 years prior with dyspnea. Patient underwent CABG and bio-prosthetic aortic valve replacement, but dyspnea persisted. PFTs showed a restrictive pattern and reduced DLCO. Chest CT showed mild centrilobular emphysema, coarse interstitial markings and bilateral pleural-parenchymal scarring with early honeycombing in the lung bases, highly suggestive of pulmonary fibrosis. Workup for secondary causes of fibrotic lung disease including connective tissue diseases and barium swallow test were negative. He was diagnosed with IPF and was started on Nintedanib within a month. Pretreatment liver function tests (LFTs) were normal. Three months into treatment, Nintedanib was discontinued due severe nausea, vomiting and diarrhea. LFTs at this time were significant for ALP 471, AST 139 and ALT 189. Liver ultrasound showed fatty infiltration and chronic liver disease workup was negative except for gamma-globulin elevation. Repeat LFTs 4 weeks after stopping Nintedanib were persistently elevated while liver biopsy showed active lobular, portal hepatitis and mild focal fibrosis. Patient was diagnosed with drug-induced autoimmune hepatitis and started on Prednisone which led to normalization of liver enzymes. Liver panel worsened when prednisone was tapered, and therefore Azathioprine was started as a steroid sparing agent. Patient continues to be on Prednisone and Azathioprine and is undergoing workup for lung transplant. LFTs improved to normal limits on current treatment. DISCUSSION: Hepatitis is a potential complication associated with Nintedanib use 4. Mechanism of hepatocellular injury remains unclear but is thought to be due to epidemiologic variances in tolerability.5 Current recommendations are to monitor LFTs every 3 months while on Nintedanib. CONCLUSIONS: A literature review did not yield other cases of Nintedanib causing drug induced autoimmune hepatitis. Nintedanib’s adverse events are still not well known, making the documentation of cases such as this one important to aid in the monitoring of patients undergoing therapy. Reference #1: Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788–824.https://doi.org/10.1164/rccm.2009-040G. Reference #2: Richeldi L , Cottin V , du Bois RM , et al . Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS(®) trials. Respir Med 2016;:74–9.https://doi.org/10.1016/j.rmed.2016.02.001 Reference #3: Richeldi L , du Bois RM , Raghu G , et al . Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014 2071;370 82:2071–82.https://doi.org/10.1056/NEJMoa1402584 DISCLOSURES: Speaker/Speaker's Bureau relationship with boehringer ingleheim Please note: $20001 - $100000 Added 03/13/2019 by Tariq Cheema, source=Web Response, value=Honoraria No relevant relationships by Muhammad Asad Faruqi, source=Web Response No relevant relationships by Ayla Gordon, source=Web Response No relevant relationships by Melissa Mosley, source=Web Response No relevant relationships by Erica Rabold, source=Web Response