Nintedanib plus sildenafil in patients with idiopathic pulmonary fibrosis

Martin Kolb, Ganesh Raghu, Athol U. Wells, Jürgen Behr, Luca Richeldi, Birgit Schinzel, Manuel Quaresma, Susanne Stowasser, Fernando J. Martinez

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Nintedanib is an approved treatment for idiopathic pulmonary fibrosis (IPF). A subgroup analysis of a previously published trial suggested that sildenafil may provide benefits regarding oxygenation, gas exchange as measured by the diffusion capacity of the lungs for carbon monoxide (DlCO), symptoms, and quality of life in patients with IPF and severely decreased DlCO. That idea was tested in this trial. METHODS: We randomly assigned, in a 1:1 ratio, patients with IPF and a DlCO of 35% or less of the predicted value to receive nintedanib at a dose of 150 mg twice daily plus sildenafil at a dose of 20 mg three times daily (nintedanib-plus-sildenafil group) or nintedanib at a dose of 150 mg twice daily plus placebo three times daily (nintedanib group) for 24 weeks. The primary end point was the change from baseline in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 12 (the total score ranges from 0 to 100, with higher scores indicating worse health-related quality of life). Secondary end points included measures of dyspnea and safety. RESULTS: A total of 274 patients underwent randomization. There was no significant difference in the adjusted mean change from baseline in the SGRQ total score at week 12 between the nintedanib-plus-sildenafil group and the nintedanib group (−1.28 points and −0.77 points, respectively; P=0.72). A benefit from sildenafil treatment was not observed with regard to dyspnea as measured with the use of the University of California, San Diego, Shortness of Breath Questionnaire. No new safety signals were observed, as compared with previous trials. CONCLUSIONS: In patients with IPF and a DlCO of 35% or less of the predicted value, nintedanib plus sildenafil did not provide a significant benefit as compared with nintedanib alone. No new safety signals were identified with either treatment regimen in this population of patients.

Original languageEnglish
Pages (from-to)1722-1731
Number of pages10
JournalNew England Journal of Medicine
Volume379
Issue number18
DOIs
Publication statusPublished - Nov 1 2018

ASJC Scopus subject areas

  • Medicine(all)

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    Kolb, M., Raghu, G., Wells, A. U., Behr, J., Richeldi, L., Schinzel, B., Quaresma, M., Stowasser, S., & Martinez, F. J. (2018). Nintedanib plus sildenafil in patients with idiopathic pulmonary fibrosis. New England Journal of Medicine, 379(18), 1722-1731. https://doi.org/10.1056/NEJMoa1811737