Log in

Nintedanib: A Review of Its Use in Patients with Idiopathic Pulmonary Fibrosis

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Nintedanib (Ofev®) inhibits receptor tyrosine kinases implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). This article reviews the efficacy and tolerability of oral nintedanib in the treatment of IPF, as well as summarizing its pharmacological properties. In the randomized, double-blind, multinational, 12-month INPULSIS-1 and -2 trials in patients with IPF, nintedanib significantly reduced the decline in forced vital capacity versus placebo, indicating a slowing of disease progression. The time to first acute exacerbation was significantly increased with nintedanib in INPULSIS-2, but not in INPULSIS-1, and significantly less deterioration in health-related quality of life was seen with nintedanib in INPULSIS-2, but not in INPULSIS-1. Nintedanib had an acceptable tolerability profile in patients with IPF; gastrointestinal adverse events (diarrhoea, nausea, vomiting) were reported most commonly. In conclusion, nintedanib is an important new option for the treatment of IPF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.

    Article  PubMed  Google Scholar 

  2. Fernandez IE, Eickelberg O. New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis. Lancet. 2012;380(9842):680–8.

    Article  CAS  PubMed  Google Scholar 

  3. King TE Jr, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet. 2011;378(9807):1949–61.

    Article  PubMed  Google Scholar 

  4. Selman M, Pardo A. Idiopathic pulmonary fibrosis: an epithelial/fibroblastic cross-talk disorder. Respir Res. 2002;3:3.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Ahluwalia N, Shea BS, Tager AM. New therapeutic targets in idiopathic pulmonary fibrosis: aiming to rein in runaway wound-healing responses. Am J Respir Crit Care Med. 2014;190(8):867–78.

    Article  CAS  PubMed  Google Scholar 

  6. Boehringer Ingelheim. Ofev® (nintedanib) capsules for oral use: US prescribing information. 2014. http://www.fda.gov/. Accessed 13 May 2015.

  7. European Medicines Agency. Ofev (nintedanib) soft capsules: EU summary of product characteristics. 2015. http://www.ema.europa.eu. Accessed 13 May 2015.

  8. Roth GJ, Binder R, Colbatzky F, et al. Nintedanib: from discovery to the clinic. J Med Chem. 2015;58(3):1053–63.

    Article  CAS  PubMed  Google Scholar 

  9. European Medicines Agency. Vargatef (nintedanib) soft capsules: EU summary of product characteristics. 2015. http://www.ema.europa.eu/. Accessed 13 May 2015.

  10. Hilberg F, Roth GJ, Krssak M, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68(12):4774–82.

    Article  CAS  PubMed  Google Scholar 

  11. Wollin L, Maillet I, Quesniaux V, et al. Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis. J Pharmacol Exp Ther. 2014;349(2):209–20.

    Article  PubMed  Google Scholar 

  12. Wollin L, Wex E, Pautsch A, et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J. 2015;45(5):1434–45.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Hostettler KE, Zhong J, Papakonstantinou E, et al. Anti-fibrotic effects of nintedanib in lung fibroblasts derived from patients with idiopathic pulmonary fibrosis. Respir Res. 2014;15(1):157.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Wollin L, Ostermann A, Wex E, et al. Nintedanib attenuates motility of lung fibroblasts from patients with idiopathic pulmonary fibrosis [abstract]. Am J Respir Crit Care Med. 2014;189:A2008.

    Google Scholar 

  15. Herrmann F, Wollin L. Nintedanib prevents IL-1β-stimulated proliferation of primary human lung fibroblasts from patients with idiopathic pulmonary fibrosis or from control donors [abstract no. P3501]. In: European Respiratory Society Congress. 2014.

  16. Hostettler KE, Papakonstantinou E, Zhong J, et al. Nintedanib (BIBF 1120) prevents TGF-β-induced pro-fibrotic effects in primary human lung myofibroblasts derived from patients with idiopathic pulmonary fibrosis [abstract no. P746]. In: European Respiratory Society Congress. 2014.

  17. Eisen T, Shparyk Y, Macleod N, et al. Effect of small angiokinase inhibitor nintedanib (BIBF 1120) on QT interval in patients with previously untreated, advanced renal cell cancer in an open-label, phase II study. Invest New Drugs. 2013;31(5):1283–93.

    Article  CAS  PubMed  Google Scholar 

  18. Ogura T, Taniguchi H, Azuma A, et al. Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2015;45(5):1382–92.

    Article  CAS  PubMed  Google Scholar 

  19. Stopfer P, Rathgen K, Liesener A. Pharmacokinetics of BIBF 1120 after administration of single doses of 100 mg [14C]-BIBF 1120 [abstract no. 478P]. Ann Oncol. 2008;19(Suppl 8):viii158.

  20. Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365(12):1079–87.

    Article  CAS  PubMed  Google Scholar 

  21. Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2071–82.

    Article  PubMed  Google Scholar 

  22. Richeldi L, Costabel U, Selman M, et al. Efficacy and safety of nintedanib in patients with IPF beyond week 52: data from the phase II TOMORROW trial [abstract]. In: American Thoracic Society 2015 International Conference. 2015.

  23. Cottin V, Taniguchi H, Collard HR, et al. Reduction in disease progression with nintedanib in the INPULSIS™ trials [abstract plus poster]. Eur Respir J. 2014;44(Suppl 58):A1906.

    Google Scholar 

  24. Costabel U, Richeldi L, Azuma A, et al. Pre-specified subgroup analyses of pooled data from the INPULSIS™ trials of nintedanib in idiopathic pulmonary fibrosis [abstract]. In: 18th International Colloquium on Lung and Airway Fibrosis. 2014.

  25. Costabel U, Inoue Y, Richeldi L, et al. Effect of baseline FVC on decline in lung function with nintedanib: results from the INPULSIS™ trials [abstract plus poster]. Eur Respir J. 2014;44(Suppl 58):A1907.

    Google Scholar 

  26. Taniguchi H, Xu Z, Azuma A, et al. Subgroup analysis of Asian patients in the Inpulsis™ trials of nintedanib in idiopathic pulmonary fibrosis [abstract no. O-I-007]. Respirology. 2014;19(Suppl 3):30.

    Google Scholar 

  27. Kolb M, Richeldi L, Kimura T, et al. Effect of baseline FVC on decline in lung function with nintedanib in patients with IPF: results from the INPULSIS® trials [abstract]. In: American Thoracic Society 2015 International Conference. 2015.

  28. Kolb M, Inoue Y, Costabel U, et al. Effect of FEV1/FVC ratio on reduction in FVC decline with nintedanib in the INPULSIS™ trials [abstract]. In: 18th International Colloquium on Lung and Airway Fibrosis. 2014.

  29. Cottin V, Taniguchi H, Richeldi L, et al. Effect of baseline emphysema on reduction in FVC decline with nintedanib in the INPULSIS™ trials [abstract]. In: 18th International Colloquium on Lung and Airway Fibrosis. 2014.

  30. Raghu G, Wells A, Nicholson AG, et al. Consistent effect of nintedanib on decline in FVC in patients across subgroups based on HRCT diagnostic criteria: results from the INPULSIS® trials in IPF [abstract]. In: American Thoracic Society 2015 International Conference. 2015.

  31. Kirsten A-M, Richeldi L, Roman J, et al. Pooled analysis of mortality data from the TOMORROW and INPULSIS® trials of nintedanib in idiopathic pulmonary fibrosis (IPF) [poster]. In: 99th Annual Meeting of the German Society for Pathology. 2015.

  32. Crestani B, Ogura T, Pelling K, et al. Safety and tolerability of nintedanib in patients with IPF: interim analysis from an open-label extension of the INPULSIS® trials (INPULSIS®-ON) [abstract]. In: American Thoracic Society 2015 International Conference. 2015.

  33. Ryerson CJ, Collard HR. Hot off the breath: a big step forward for idiopathic pulmonary fibrosis. Thorax. 2014;69(9):791–2.

    Article  PubMed  Google Scholar 

  34. Boehringer Ingelheim. Boehringer Ingelheim welcomes the update of the ATS/ERS/JRS/ALAT 2011 evidence based guidelines for treatment of idiopathic pulmonary fibrosis (IPF), suggesting nintedanib for the treatment of IPF [media release]. 2015. www.boehringer-ingelheim.com. Accessed 27 May 2015.

  35. Nathan SD, Meyer KC. IPF clinical trial design and endpoints. Curr Opin Pulm Med. 2014;20(5):463–71.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Crooks MG, Hart SP. A new era of drug therapy for idiopathic pulmonary fibrosis. Lancet Respir Med. 2014;2(12):964–6.

    Article  PubMed  Google Scholar 

  37. Karimi-Shah BA, Chowdhury BA. Forced vital capacity in idiopathic pulmonary fibrosis: FDA review of pirfenidone and nintedanib. N Engl J Med. 2015;372(13):1189–91.

    Article  PubMed  Google Scholar 

  38. Ryerson CJ, Collard HR. Acute exacerbations complicating interstitial lung disease. Curr Opin Pulm Med. 2014;20(5):436–41.

    Article  PubMed  Google Scholar 

  39. Hunninghake GM. A new hope for idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2142–3.

    Article  CAS  PubMed  Google Scholar 

  40. InterMune Inc. Esbriet® (pirfenidone) capsules: US prescribing information. 2014. http://www.esbriet.com/. Accessed 13 May 2015.

  41. European Medicines Agency. Esbriet (pifenidone) hard capsules: EU summary of product characteristics. 2015. http://www.ema.europa.eu. Accessed 13 May 2015.

  42. Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377(9779):1760–9.

    Article  CAS  PubMed  Google Scholar 

  43. King TE, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083–92.

    Article  PubMed  Google Scholar 

  44. Taniguchi H, Ebina M, Kondoh Y, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2010;35(4):821–9.

    Article  CAS  PubMed  Google Scholar 

  45. Costabel U, Bendstrup E, Cottin V, et al. Pirfenidone in idiopathic pulmonary fibrosis: expert panel discussion on the management of drug-related adverse events. Adv Ther. 2014;31(4):375–91.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Wuyts WA, Antoniou KM, Borensztajn K, et al. Combination therapy: the future of management for idiopathic pulmonary fibrosis? Lancet Respir Med. 2014;2(11):933–42.

    Article  PubMed  Google Scholar 

Download references

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit. Gillian Keating is a salaried employee of Adis/Springer.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gillian M. Keating.

Additional information

The manuscript was reviewed by: P. S. Burge, Occupational Lung Disease Unit, Birmingham Heartlands Hospital, Birmingham, UK; L. Hagmeyer, Clinic for Pneumology and Allergology, Center of Sleep Medicine and Respiratory Care, Bethanien Hospital, Solingen, Germany; N. Sandbo, Division of Allergy, Pulmonary, and Critical Care, University of Wisconsin-Madison, Madison, WI, USA.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Keating, G.M. Nintedanib: A Review of Its Use in Patients with Idiopathic Pulmonary Fibrosis. Drugs 75, 1131–1140 (2015). https://doi.org/10.1007/s40265-015-0418-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-015-0418-6

Keywords

Navigation