title: Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis is a progressive lung disease with a high mortality rate. Because the signaling pathways activated by several tyrosine kinase receptors have been shown to be involved in lung fibrosis, it has been suggested that the inhibition of these receptors may slow the progression of idiopathic pulmonary fibrosis.
  
  
  METHODS
  In a 12-month, phase 2 trial, we assessed the efficacy and safety of four different oral doses of the tyrosine kinase inhibitor BIBF 1120 as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Secondary end points included acute exacerbations, quality of life (measured with the St. George's Respiratory Questionnaire [SGRQ]), and total lung capacity.
  
  
  RESULTS
  A total of 432 patients underwent randomization to receive one of four doses of BIBF 1120 (50 mg once a day, 50 mg twice a day, 100 mg twice a day, or 150 mg twice a day) or placebo. In the group receiving 150 mg of BIBF 1120 twice a day, FVC declined by 0.06 liters per year, as compared with 0.19 liters per year in the placebo group, a 68.4% reduction in the rate of loss with BIBF 1120 (P = 0.06 with the closed testing procedure for multiplicity correction; P = 0.01 with the hierarchical testing procedure). This dose also resulted in a lower incidence of acute exacerbations, as compared with placebo (2.4 vs. 15.7 per 100 patient-years, P = 0.02) and a small decrease in the SGRQ score (assessed on a scale of 0 to 100, with lower scores indicating better quality of life) as compared with an increase with placebo (-0.66 vs. 5.46, P = 0.007). Gastrointestinal symptoms (which led to more discontinuations in the group receiving 150 mg twice a day than in the placebo group) and increases in levels of liver aminotransferases were more frequent in the group receiving 150 mg of BIBF 1120 twice daily than in the placebo group.
  
  
  CONCLUSIONS
  In patients with idiopathic pulmonary fibrosis, BIBF 1120 at a dose of 150 mg twice daily, as compared with placebo, was associated with a trend toward a reduction in the decline in lung function, with fewer acute exacerbations and preserved quality of life. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00514683 .).
authors: Center for Rare Lung Diseases, University of Modena and Reggio Emilia, Policlinico Hospital, Modena, Italy. luca.richeldi@unimore.it
authors: Luca
authors: L
authors: Richeldi
authors: Ulrich
authors: U
authors: Costabel
authors: Moises
authors: M
authors: Selman
authors: Dong Soon
authors: DS
authors: Kim
authors: David M
authors: DM
authors: Hansell
authors: Andrew G
authors: AG
authors: Nicholson
authors: Kevin K
authors: KK
authors: Brown
authors: Kevin R
authors: KR
authors: Flaherty
authors: Paul W
authors: PW
authors: Noble
authors: Ganesh
authors: G
authors: Raghu
authors: Michèle
authors: M
authors: Brun
authors: Abhya
authors: A
authors: Gupta
authors: Nolwenn
authors: N
authors: Juhel
authors: Matthias
authors: M
authors: Klüglich
authors: Roland M
authors: RM
authors: du Bois
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014797:Vital Capacity
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D011505:Protein-Tyrosine Kinases; C530716:nintedanib