Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary fibrosis

Eur Respir J. 2018 Aug 2;52(2):1800230. doi: 10.1183/13993003.00230-2018. Print 2018 Aug.


We assessed safety and tolerability of treatment with pirfenidone (1602-2403 mg·day-1) and nintedanib (200-300 mg·day-1) in patients with idiopathic pulmonary fibrosis (IPF).This 24-week, single-arm, open-label, phase IV study ( identifier NCT02598193) enrolled patients with IPF with forced vital capacity % pred ≥50% and diffusing capacity of the lung for carbon monoxide % pred ≥30%. Before initiating nintedanib, patients had received pirfenidone for ≥16 weeks and tolerated a stable dose of ≥1602 mg·day-1 for ≥28 days. The primary end-point was the proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602-2403 mg·day-1) and nintedanib (200-300 mg·day-1). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither.89 patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end-point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the most common. Two patients had serious treatment-related TEAEs.Combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF and associated with a similar pattern of TEAEs expected for either treatment alone. These results encourage further study of combination treatment with pirfenidone and nintedanib in patients with IPF.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Drug Therapy, Combination
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Indoles / administration & dosage*
  • Indoles / adverse effects
  • Internationality
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Pyridones / administration & dosage*
  • Pyridones / adverse effects
  • Treatment Outcome
  • Vital Capacity


  • Anti-Inflammatory Agents, Non-Steroidal
  • Indoles
  • Pyridones
  • pirfenidone
  • nintedanib

Associated data