title: Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS(®) trials.
abstract: OBJECTIVE
  The Phase II TOMORROW trial and two Phase III INPULSIS(®) trials investigated the efficacy and safety of nintedanib versus placebo in patients with idiopathic pulmonary fibrosis (IPF). To obtain an overall estimate of the treatment effect of nintedanib 150 mg twice daily (bid), pooled and meta-analyses of data from these three trials were conducted.
  
  
  METHODS
  Pooled and meta-analyses were conducted for annual rate of decline in forced vital capacity (FVC), time to first acute exacerbation, change from baseline in St George's Respiratory Questionnaire (SGRQ) total score and mortality over 52 weeks.
  
  
  RESULTS
  1231 patients (nintedanib n = 723, placebo n = 508) were included in the pooled analysis. Adjusted annual rate of decline in FVC was -112.4 mL/year with nintedanib and -223.3 mL/year with placebo (difference: 110.9 mL/year [95% CI: 78.5, 143.3]; p < 0.0001). The hazard ratio for time to first acute exacerbation was 0.53 (95% CI: 0.34, 0.83; p = 0.0047). Adjusted mean change from baseline in SGRQ score at week 52 was 2.92 with nintedanib and 4.97 with placebo (difference: -2.05 [95% CI: -3.59, -0.50]; p = 0.0095). Hazard ratios for time to all-cause and on-treatment mortality were 0.70 (95% CI: 0.46, 1.08; p = 0.0954) and 0.57 (95% CI: 0.34, 0.97; p = 0.0274), respectively, in favour of nintedanib. The meta-analysis was generally consistent with the pooled analysis. Diarrhoea was the most frequent adverse event in the nintedanib group (61.5% of patients treated with nintedanib versus 17.9% of patients treated with placebo).
  
  
  CONCLUSIONS
  Nintedanib has a beneficial effect on slowing disease progression in patients with IPF.
authors.affiliation: National Institute for Health Research, Southampton Respiratory Biomedical Research Unit and Clinical and Experimental Sciences, University of Southampton, University Road, Southampton, SO17 1BJ, UK. Electronic address: L.Richeldi@soton.ac.uk.
authors.forename: Luca
authors.initials: L
authors.lastname: Richeldi
authors.affiliation: Louis Pradel Hospital, Claude Bernard University Lyon 1, 28 Avenue du Doyen Lepine, 69677, Bron Cedex, Lyon, France. Electronic address: vincent.cottin@chu-lyon.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cottin
authors.affiliation: Imperial College, London, SW7 2AZ, UK. Electronic address: ron@du-bois.co.uk.
authors.forename: Roland M
authors.initials: RM
authors.lastname: du Bois
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias, Calz. de Tlalpan 4502, Tlalpan, Mexico City, D.F., Mexico. Electronic address: mselmanl@yahoo.com.mx.
authors.forename: Moisés
authors.initials: M
authors.lastname: Selman
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216, Ingelheim am Rhein, Germany. Electronic address: toshio.kimura@boehringer-ingelheim.com.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Boehringer Ingelheim Ltd., Ellesfield Avenue, Bracknell, West Berkshire, RG12 8YS, UK. Electronic address: zelie.bailes@boehringer-ingelheim.com.
authors.forename: Zelie
authors.initials: Z
authors.lastname: Bailes
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, 06877, USA. Electronic address: rozsa.schlenker-herceg@boehringer-ingelheim.com.
authors.forename: Rozsa
authors.initials: R
authors.lastname: Schlenker-Herceg
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216, Ingelheim am Rhein, Germany. Electronic address: susanne.stowasser@boehringer-ingelheim.com.
authors.forename: Susanne
authors.initials: S
authors.lastname: Stowasser
authors.affiliation: National Jewish Health, 1400 Jackson St, Denver, CO, 80206, USA. Electronic address: brownk@njhealth.org.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Brown
mesh_terms: D000368:Aged; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; C530716:nintedanib
keywords: Acute exacerbations; Disease progression; Forced vital capacity; Mortality; Quality of life