title: Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterised by dyspnea and loss of lung function.
  
  
  METHODS
  Using pooled data from the replicate, randomized, 52-week, placebo-controlled INPULSIS(®) trials, we characterized the safety and tolerability of nintedanib 150 mg twice daily in patients with IPF and described how adverse events were managed during these trials.
  
  
  RESULTS
  One thousand and sixty- one patients were treated (nintedanib 638; placebo 423). Higher proportions of patients in the nintedanib group than the placebo group had ≥ 1 dose reduction to 100 mg bid (27.9% versus 3.8%) or treatment interruption (23.7% versus 9.9%). Adverse events led to permanent treatment discontinuation in 19.3% and 13.0% of patients in the nintedanib and placebo groups, respectively. Diarrhea was the most frequent adverse event, reported in 62.4% of patients in the nintedanib group versus 18.4% in the placebo group; however, only 4.4% of nintedanib-treated patients discontinued trial medication prematurely due to diarrhea. Monitoring of liver enzymes before and periodically during nintedanib treatment was recommended so that liver enzyme elevations could be managed through dose reduction or treatment interruption.
  
  
  CONCLUSIONS
  Nintedanib had a manageable safety and tolerability profile in patients with IPF. Recommendations for adverse event management minimized permanent treatment discontinuations in the INPULSIS(®) trials.
  
  
  BACKGROUND
  clinicaltrials.gov NCT01335464 and NCT01335477.
authors.affiliation: Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. tameracorte@mac.com.|University of Sydney, Sydney, New South Wales, Australia. tameracorte@mac.com.
authors.forename: Tamera
authors.initials: T
authors.lastname: Corte
authors.affiliation: Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany. francesco.bonella@ruhrlandklinik.uk-essen.de.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonella
authors.affiliation: Hôpital Bichat, Pneumologie, Paris, France. bruno.crestani@bch.aphp.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Crestani
authors.affiliation: University Hospital Leuven, Leuven, Belgium. maurits.demedts@uz.kuleuven.ac.be.
authors.forename: Maurits G
authors.initials: MG
authors.lastname: Demedts
authors.affiliation: National Institute for Health Research Southampton Respiratory Biomedical Research Unit and Clinical and Experimental Sciences, University of Southampton, Southampton, UK. l.richeldi@soton.ac.uk.
authors.forename: Luca
authors.initials: L
authors.lastname: Richeldi
authors.affiliation: SCS Boehringer Ingelheim Comm.V., Brussels, Belgium. carl.coeck@boehringer-ingelheim.com.
authors.forename: Carl
authors.initials: C
authors.lastname: Coeck
authors.affiliation: Boehringer Ingelheim Ltd., Bracknell, UK. katy.pelling@boehringer-ingelheim.com.
authors.forename: Katy
authors.initials: K
authors.lastname: Pelling
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. manuel.quaresma@boehringer-ingelheim.com.
authors.forename: Manuel
authors.initials: M
authors.lastname: Quaresma
authors.affiliation: Tulane University School of Medicine, New Orleans, LA, USA. jlasky@tulane.edu.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lasky
mesh_terms: D000368:Aged; D017326:Clinical Trials, Phase III as Topic; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; C530716:nintedanib