Abstract
We used data from the INBUILD and INPULSIS trials to investigate the natural history of progressive fibrosing interstitial lung diseases (ILDs).
Subjects in the two INPULSIS trials had a clinical diagnosis of idiopathic pulmonary fibrosis (IPF) while subjects in the INBUILD trial had a progressive fibrosing ILD other than IPF and met protocol-defined criteria for ILD progression despite management. Using data from the placebo groups, we compared the rate of decline in forced vital capacity (FVC) (mL·year−1) and mortality over 52 weeks in the INBUILD trial with pooled data from the INPULSIS trials.
The adjusted mean annual rate of decline in FVC in the INBUILD trial (n=331) was similar to that observed in the INPULSIS trials (n=423) (−192.9 and −221.0 mL·year−1, respectively; nominal p-value: 0.19). The proportion of subjects who had a relative decline in FVC >10% predicted at week 52 was 48.9% in the INBUILD trial and 48.7% in the INPULSIS trials, and the proportion who died over 52 weeks was 5.1% in the INBUILD trial and 7.8% in the INPULSIS trials. A relative decline in FVC >10% predicted was associated with an increased risk of death in the INBUILD (hazard ratio 3.64) and INPULSIS (hazard ratio 3.95) trials.
These findings indicate that patients with fibrosing ILDs other than IPF, who are progressing despite management, have a subsequent clinical course similar to patients with untreated IPF, with a high risk of further ILD progression and early mortality.
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.
Conflict of interest: Dr. Brown reports the following outside the submitted work: grants from NIH, and advisory board participation for the following Biogen, Blade, Boehringer Ingelheim, Galapagos, Galecto, Genoa, Lifemax, MedImmune, monARC Bionetworks, OSIC (Open Source Imaging Consortium), Pliant, ProMetic, Third Pole, Theravance, Three Lakes Partners, Veracyte.
Conflict of interest: Dr. Martinez reports grants from Department of Defense, during the conduct of the study; personal fees, non-financial support and other from AstraZeneca, personal fees, non-financial support and other from Boehringer Ingelheim, non-financial support and other from ProterrixBio, personal fees from Columbia University, personal fees and non-financial support from Genentech, personal fees and non-financial support from GlaxoSmithKline, personal fees and non-financial support from Inova Fairfax Health System, personal fees from MD Magazine, personal fees from Methodist Hospital Brooklyn, personal fees and non-financial support from Miller Communicatinos, personal fees and non-financial support from National Association for Continuing Education, personal fees and non-financial support from Novartis, personal fees from New York University, personal fees and non-financial support from Pearl Pharmaceuticals, personal fees and non-financial support from PeerView Communications, personal fees and non-financial support from Prime Communications, personal fees and non-financial support from Puerto Rican Respiratory Society, personal fees and non-financial support from Chiesi, personal fees and non-financial support from Sunovion, personal fees and non-financial support from Theravance, personal fees from UpToDate, personal fees from WebMD/MedScape, other from Afferent/Merck, non-financial support from Gilead, non-financial support from Nitto, personal fees and other from Patara/Respivant, personal fees and non-financial support from Potomac, other from Biogen, personal fees and non-financial support from University of Alabama Birmingham, other from Veracyte, non-financial support from Zambon, personal fees from American Thoracic Society, grants from NIH, personal fees and non-financial support from Physicians Education Resource, personal fees from Rockpointe, other from Prometic, personal fees from Rare Disease Healthcare Communications, other from Bayer, other from Bridge Biotherapeutics, personal fees and non-financial support from Canadian Respiratory Network, other from ProMedior, personal fees and non-financial support from Teva, personal fees from France Foundation, personal fees and non-financial support from Dartmouth, other from Gala, personal fees from Physicians Education Resource, outside the submitted work.
Conflict of interest: Dr. Walsh reports personal fees from Sanofi-Aventis, personal fees from Roche, grants and personal fees from Boehringer Ingelheim, personal fees from Galapagos, personal fees from OSIC, personal fees from Bracco, outside the submitted work.
Conflict of interest: Dr. Thannickal reports personal fees from Boehringer Ingelheim Pharmaceuticals, Inc, personal fees from Kadmon Corporation, grants from Genkyotex, personal fees from Pliant, personal fees from Glenmark, personal fees from Covance, personal fees from Blade, personal fees from Versant Venture, personal fees from Mistral, outside the submitted work.
Conflict of interest: Dr. Prasse reports other from Boehriinger Ingelheim, during the conduct of the study; personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial support from Roche, personal fees and non-financial support from Novartis, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Chiesi, personal fees and non-financial support from Nitto Denko, personal fees and non-financial support from Pliant, outside the submitted work.
Conflict of interest: The author (Rozsa Schlenker-Herceg) is an employee of Boehringer Ingelheim Pharmaceuticals, Inc.
Conflict of interest: The author (Rainer-Georg Goeldner) is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG.
Conflict of interest: The author (Emmanuelle Clerisme-Beaty) is an employee of Boehringer Ingelheim International GmbH.
Conflict of interest: The author (Kay Tetzlaff) is an employee of Boehringer Ingelheim International GmbH.
Conflict of interest: Dr. Cottin reports personal fees and non-financial support from Actelion, grants, personal fees and non-financial support from Boehringer Ingelheim, personal fees from Bayer / MSD, personal fees from Gilead, personal fees from Novartis, grants, personal fees and non-financial support from Roche, personal fees from Sanofi, personal fees from Promedior, personal fees from Celgene, personal fees from Galapagos, personal fees from Galecto, outside the submitted work.
Conflict of interest: Dr. Wells reports personal fees from Boehringer Ingelheim, personal fees from Roche, personal fees from Blade, outside the submitted work.
- Received January 15, 2020.
- Accepted February 20, 2020.
- Copyright ©ERS 2020