Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS(®) trials

Respir Med. 2016 Apr:113:74-9. doi: 10.1016/j.rmed.2016.02.001. Epub 2016 Feb 3.


Background and purpose: 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).

Conclusion: Nintedanib has a beneficial effect on slowing disease progression in patients with IPF.

Keywords: Acute exacerbations; Disease progression; Forced vital capacity; Mortality; Quality of life.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Diarrhea / chemically induced
  • Drug Administration Schedule
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Indoles / administration & dosage*
  • Indoles / pharmacology
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Vital Capacity / drug effects


  • Enzyme Inhibitors
  • Indoles
  • nintedanib