Safety of Nintedanib Added to Pirfenidone Treatment for Idiopathic Pulmonary Fibrosis

  1. Kevin R. Flaherty1,
  2. Charlene D. Fell2,
  3. J. Terrill Huggins3,
  4. Hilario Nunes4,
  5. Robert Sussman5,
  6. Claudia Valenzuela6,
  7. Ute Petzinger7,
  8. John L. Stauffer8,
  9. Frank Gilberg9,
  10. Monica Bengus9 and
  11. Marlies Wijsenbeek10
  1. 1Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA
  2. 2Division of Respirology, University of Calgary, Calgary, AB, Canada
  3. 3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, SC, USA
  4. 4Department of Respiratory Medicine, EA2363, Avicenne University Hospital, Paris, France
  5. 5Atlantic Health System, Overlook Medical Center, Summit, NJ, USA
  6. 6Servicio de Neumología, Hospital Universitario de La Princesa, Instituto de Investigación Princesa, Madrid, Spain
  7. 7Clinipace-Accovion GmbH, Eschborn, Germany
  8. 8Genentech, Inc., South San Francisco, CA, USA
  9. 9F. Hoffmann-La Roche, Ltd., Basel, Switzerland
  10. 10Department of Respiratory Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
  1. Kevin R. Flaherty, 1500 E. Medical Center Drive, 3916 Taubman Center, Ann Arbor, MI 48109, USA. E-mail: flaherty{at}med.umich.edu

Abstract

We assessed safety and tolerability of treatment with pirfenidone (1602–2403 mg/day) and nintedanib (200–300 mg/day) in patients with idiopathic pulmonary fibrosis (IPF).

This 24-week, single-arm, open-label Phase IV study (NCT02598193) enrolled patients with IPF with forced vital capacity (FVC) ≥50% and carbon monoxide diffusing capacity (DLco) ≥30%. Before initiating nintedanib, patients had received pirfenidone for ≥16 weeks and tolerated a stable dose of ≥1602 mg/day for ≥28 days. The primary endpoint was proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602–2403 mg/day) and nintedanib (200–300 mg/day). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither.

Eighty-nine patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary endpoint) and 16 discontinued treatment prematurely (13 due to TEAEs). Seventy-four 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.

Abstract

Combined pirfenidone and nintedanib was tolerated by the majority of patients with IPF, encouraging further study

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflicts of interests: This trial was funded by F. Hoffmann-La Roche, Ltd. K.R.F. has received consultant and research support fees from F. Hoffmann-La Roche/Genentech and Boehringer Ingelheim, consultant fees from FibroGen, Veracyte, Aeolus, PharmaKea, Sanofi-Genzyme and Celgene and research support fees from Afferent Pharmaceuticals. C.D.F. has received consultant and research support fees from F. Hoffmann-La Roche Canada and consultant fees from Boehringer Ingelheim. J.T.H has received consultant and research support fees from F. Hoffmann-La Roche/Genentech and Boehringer Ingelheim, and consultant fees from Gilead and iBIOS. H.N. has received consultant and research support fees from F. Hoffmann-La Roche/Genentech and Boehringer Ingelheim, and has been an investigator of clinical trials for Sanofi and Gilead. R.S. has received research support and speaker and consultation fees from F. Hoffmann-La Roche/Genentech and Boehringer Ingelheim, and research support from Gilead. C.V. has received speaker and consultation fees from F. Hoffmann-La Roche and Boehringer Ingelheim. U.P. has no conflicts of interest relevant to this paper. J.L.S. is an employee of Genentech and a former employee of FibroGen, and holds shares from both. F.G. and M.B. are employees of F. Hoffmann-La Roche. M.W. has received speaker and consultation fees and unrestricted research grants from F. Hoffmann-La Roche and Boehringer Ingelheim, and consultancy fees from Galapagos; all fees and grants were paid to her institution.

Conflict of interest: Dr. Flaherty reports grants and personal fees from Roche/Genentech, personal fees from FibroGen, grants from Afferent Pharmaceuticals, grants and personal fees from Boehringer lngelheim, personal fees from Veracyte, personal fees from Aeolus, personal fees from Pharmakea, personal fees from Sanofi-Genzyme, personal fees from Celgene, outside the submitted work;.

Conflict of interest: Charlene D. Fell

Conflict of interest: J. Terrill Huggins

Conflict of interest: Hilario Nunes

Conflict of interest: Robert Sussman

Conflict of interest: Claudia Valenzuela

Conflict of interest: Ute Petzinger

Conflict of interest: John L. Stauffer

Conflict of interest: Frank Gilberg

Conflict of interest: Monica Bengus

Conflict of interest: Marlies Wijsenbeek

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