THE CASE OF ASCENDING PARAPARESIS FOLLOWING NINTEDANIB

Abstract

SESSION TITLE: Fellows Diffuse Lung Disease SESSION TYPE: Fellow Case Reports PRESENTED ON: October 18-21, 2020 INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an incurable, progressive fibrosing interstitial lung disease reflected by a decline in lung function, worsening dyspnea, exercise capacity, and overall poor prognosis. Nintedanib is one of two anti-fibrotic therapies approved for the treatment of IPF. We present the case of a patient who presented with ascending paraparesis following Nintedanib and here by hope to shed light on treatment of IPF and potential but unproven side effects of Nintedanib. CASE PRESENTATION: 39-year-old male with history of familial IPF secondary to short telomere syndrome who presented with bilateral progressive upper and lower extremity paresthesia and weakness which started shortly after he was commenced on Nintedanib for pulmonary fibrosis. This progressed to numbness and weakness till he could barely walk or lift his arms against gravity by day 5. He denied any preceding upper respiratory tract or gastrointestinal symptoms. Physical exam was significant for bibasilar fine velcro crackles in the lungs, hyporeflexia and flaccid tone with power of 3/5 in all extremities. He had negative autoimmune work up. Cerebro-spinal fluid analysis, Pan spinal MRI and MRI of the brain were unrevealing. Electromyogram was significant for motor polyneuropathy with limited demyelinating features. Management was mainly supportive with physical therapy and patient gradually regained his strength back to baseline. DISCUSSION: Nintedanib inhibits multiple tyrosine kinases and targets growth factors like vascular endothelial growth factor receptor, fibroblast growth factor receptor and platelet-derived growth factor receptor which have been implicated in the pathogenesis of idiopathic pulmonary fibrosis. It is important to monitor potential adverse effects aside from what was noted in the relevant trials of which diarrhea was the commonest. Other side effects were bronchitis, upper respiratory tract symptoms, nausea, vomiting, cough weight loss and back ache. Our patient presented with paresthesias and ascending paresis after taking Nintadenib. He had negative extensive work up for other causes of ascending paralysis and his weakness gradually improved after stopping the medication and with Physical therapy. He was initially offered Intravenous immunoglobulin but was already improving clinically with supportive therapy and physical therapy, so after weighing risk to benefit, decided against it. CONCLUSIONS: With the widening use of Nintedanib, more patients will undoubtedly be exposed to it, and providers should be aware of this unlikely, but serious, potential side effect of Guillain-Barre like presentation which has been associated with other tyrosine kinase inhibitors. To the best of our knowledge, this is the first reported case of ascending paresis following the use of Nintedanib in particular. Reference #1: Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis. (2015). New England Journal Of Medicine, 373(8), 782-782. doi: 10.1056/nejmx150012 Reference #2: "Human Medicines European Public Assessment Report (EPAR): Ofev, Nintedanib, Idiopathic Pulmonary Fibrosis, Date Of Authorisation: 14/01/2015, Revision: 10, Status: Authorised". 2019. Case Journals, doi:10.31525/cmr-587247. Reference #3: Lehky, T. J. et al. "Neuromuscular Junction Toxicity With Tandutinib Induces A Myasthenic-Like Syndrome". Neurology, vol 76, no. 3, 2011, pp. 236-241. Ovid Technologies (Wolters Kluwer Health), doi:10.1212/wnl.0b013e3182074a69. DISCLOSURES: No relevant relationships by Shehabaldin Alqalyoobi, source=Web Response No relevant relationships by Afua Kunadu, source=Web Response No relevant relationships by Ogugua Obi, source=Web Response