Estás en: Inicio > Congresos > Resúmenes > ATS 2015

Efficacy and Safety of Nintedanib in Patients with IPF Beyond Week 52: Data from The Phase II TOMORROW Trial
[Publication Page: A1019]

L. Richeldi, MD, PhD, U. Costabel, MD, M. Selman, MD, Z. Xu, MD, T. Kimura, MPH, S. Stowasser, MD, C. Hallmann, MD, R.M. Du Bois, MD. Southampton/UK, Essen/DE, Mexico City/MX, Beijing/CN, Ingelheim Am Rhein/DE, London/UK.

Am J Respir Crit Care Med 191;2015:A1019.

Period 1 of the TOMORROW trial was a phase II, randomized, placebo-controlled trial of four doses of nintedanib (50 mg qd, 50 mg bid, 100 mg bid, 150 mg bid) in patients with idiopathic pulmonary fibrosis (IPF) over 52 weeks. Results suggested that nintedanib 150 mg bid was associated with a reduced decline in forced vital capacity (FVC) and fewer acute exacerbations versus placebo. After completing period 1, patients had the option to continue treatment in a further blinded treatment phase (period 2).

Safety and Tolerability of Nintedanib in Patients with IPF: Interim Analysis from an Open-Label Extension of The INPULSIS® Trials (INPULSIS®-ON)
[Publication Page: A1020]

B. Crestani, MD, PhD, T. Ogura, MD, K. Pelling, MSc, M. Quaresma, PharmD, C. Coeck, MD, M. Kaye, MD. Paris/FR, Yokohama, Kanagawa/JP, Bracknell/UK, Ingelheim Am Rhein/DE, Brussels/BE, Minneapolis, MN/US.

Am J Respir Crit Care Med 191;2015:A1020.

The two replicate, 52-week INPULSIS® trials assessed the efficacy and safety of nintedanib 150 mg twice daily (bid) in patients with idiopathic pulmonary fibrosis (IPF). Dose reduction to 100 mg bid was allowed for management of adverse events; re-escalation to 150 mg bid was allowed within 4 weeks of dose reduction. The primary endpoint was met in both trials; nintedanib significantly reduced the annual rate of decline in FVC compared with placebo, consistent with a slowing of disease progression. Patients who completed the 52-week treatment period and a follow-up visit 4 weeks later could elect to receive open-label nintedanib as part of an extension trial to assess the long-term safety and tolerability of nintedanib.

Effect of Baseline FVC on Decline in Lung Function with Nintedanib in Patients with IPF: Results from The INPULSIS® Trials
[Publication Page: A1021]

M. Kolb, MD, L. Richeldi, MD, PhD, T. Kimura, MPH, S. Stowasser, MD, C. Hallmann, MD, R.M. Du Bois, MD Hamilton. ON/CA, Southampton/UK, Ingelheim Am Rhein/DE, London/UK.

Am J Respir Crit Care Med 191;2015:A1021.

The two replicate, randomized, placebo-controlled, 52-week Phase III INPULSIS® trials assessed the efficacy and safety of nintedanib 150 mg twice daily (bid) in patients with idiopathic pulmonary fibrosis (IPF). Patients with forced vital capacity (FVC) ≥50% predicted were included. The primary endpoint, the annual rate of decline in FVC, was significantly reduced in the nintedanib group compared with placebo in both trials, consistent with a slowing of disease progression. Key secondary endpoints were time to first acute exacerbation and change from baseline in St. George’s Respiratory Questionnaire total score, both over 52 weeks. In a pre-specified subgroup analysis of patients with baseline FVC ≤70% versus >70% predicted, the treatment effect of nintedanib on decline in FVC was consistent in both subgroups.

Consistent Effect of Nintedanib on Decline in FVC in Patients Across Subgroups Based on HRCT Diagnostic Criteria: Results from The INPULSIS® Trials in IPF
[Publication Page: A1022]

G. Raghu, MD, A. Wells, MD, A.G. Nicholson, DM, L. Richeldi, MD, PhD, K.R. Flaherty, MD, F. Le Maulf, MSc, S. Stowasser, MD, R. Schlenker-Herceg, MD, D.M. Hansell, MD. Seattle, WA/US, London/UK, Southampton/UK, Ann Arbor, MI/US, Reims/FR, Ingelheim Am Rhein/DE, Ridgefield, CT/US.

Am J Respir Crit Care Med 191;2015:A1022.

The two replicate, randomized, placebo-controlled, 52-week INPULSIS® trials assessed the efficacy and safety of nintedanib 150 mg twice daily (bid) in patients with IPF. The primary endpoint was met in both trials; nintedanibsignificantly reduced the annual rate of decline in FVC compared with placebo, consistent with a slowing of disease progression. Key secondary endpoints were time to first acute exacerbation and change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score, both over 52 weeks.


Vasorelaxant Properties of Nintedanib in the Murine Pulmonary Circulation
[Publication Number: A1956]

A.D. Rieg, MD, L. Wollin, PhD, J. Krabbe, MD, S. Uhlig, Ph.D., C. Martin, Ph.D. Aachen/DE, Biberach/DE, 2418089122/DE. Am J Respir Crit Care Med 191;2015:A1956. 

Idiopathic pulmonary fibrosis (IPF) is a progressive, severely debilitating disease with high mortality. Pulmonary arterial hypertension (PAH) is common in patients with IPF and significantly impacts survival. In two replicate Phase III clinical trials (INPULSIS-1 and -2) in patients with IPF, nintedanib reduced the decline in forced vital capacity (FVC) which is consistent with a slowing of disease progression. The mode of action of nintedanib suggests that it may also affect PAH. We used murine pulmonary arteries and veins pre-contracted with endothelin-1 (ET-1) to determine the acute vasorelaxant effects of nintedanib.

TGF-β Affects Nintedanib Function via PDGFRα in Primary Human Fibroblasts
[Publication Number: A2363]

K. Heinzelmann, PhD, N. Noskovicova, M.Sc., J. Merl-Pham, Dr., M. Lindner, Dr., R. Hatz, Prof., J. Behr, Prof., S.M. Hauck, Dr.,O. Eickelberg, Prof. Munich/DE. 

Am J Respir Crit Care Med 191;2015:A2363

Idiopathic pulmonary fibrosis (IPF) is characterized by altered cell activation, as well as tissue remodeling, resulting in increased extracellular matrix (ECM) deposition. Fibroblasts are thought to be the most important ECM-producing cell type in the lung, but specific cell surface patterns of lung fibroblasts remain elusive. An increase of TGF-β activity is strongly associated with IPF, however, its precise influence on the fibroblast surface proteome has not been studied yet.

Anti-Fibrotic Effects of Nintedanib on Lung Fibroblasts
[Publication Number: A2365]

S. Rangarajan, MD, A. Kurundkar, Doctor of Medicine, D. Kurundkar, MD, K. Bernard, PhD, Y. Sanders, MD, Q. Ding, PhD, J. Zhang, Ph D, J. Zmijewski, Ph D, V.J. Thannickal, MD. Birmingham, AL/US. 

Am J Respir Crit Care Med 191;2015:A2365.

Idiopathic pulmonary fibrosis (IPF) is a disease with relentless course and limited therapeutic options. Nintedanib, a multiple receptor tyrosine kinase inhibitor has recently been approved by U.S. Food and Drug Administration (FDA) for use in IPF; its putative anti-fibrotic mechanisms of action are unclear. We investigated the potential anti-fibrotic effects of Nintedanib on lung fibroblasts, key effector cells in pathogenesis of fibrosis.

PBI-4050 Reduces Inflammatory/Fibrotic Markers in A Bleomycin-Induced Lung Fibrosis Model: A Comparative Study with Nintedanib
[Publication Number: A3468]

L. Gagnon, Ph.D., M. Tremblay, Technician, F. Sarra-Bournet, Technician, A. Felton, Technician, L. Gervais, Technician, M. Leduc, Ph.D., S. Abbott, Ph.D., J.-S. Duceppe, M.Sc., B. Zacharie, Ph.D., P. Laurin, M.Sc., B. Grouix, Ph.D. Laval. QC/CA.

Am J Respir Crit Care Med 191;2015:A3468.

Idiopathic pulmonary fibrosis is a progressive and lethal lung disease with limited therapeutic options. The aim of this study was to compare the effect of the first-in-class anti-inflammatory/fibrotic compound PBI-4050, presently in clinical phase II, and the tyrosine kinase inhibitor Nintedanib (formerly BIBF1120), and combination of both compounds in the bleomycin-induced lung fibrosis model.


 

Effects of Nintedanib on the Microvascular Architecture in a Bleomycin-induced Pulmonray Fibrosis Model
[Publication Number: A4395]

M. Ackermann, MD, Y.O. Kim, PhD, D. Schuppan, MD, PhD, S. Kreuz, PhD, D. Stiller, PhD, L. Wollin, PhD, M.A. Konerding, MD. Mainz/DE, Boston, MA/US, Biberach/DE. Am J Respir Crit Care Med 191;2015:A4395

Idiopathic pulmonary fibrosis (IPF) is a progressive, severely debilitating disease wih a high mortality rate. Excessive fibrosis with depositon of extracellular matrix but also microvasuar alterations are described in the lung pathobiology of IPF. Nintedanib is a tyrosine kinase inhibitor for the treatment of IPF with anti-fibrotic, anti-inflammatory but also anti-angiogenic activity. In two replicate Phase III clinical trials (INPULSIS-1 and -2) in patients with IPF, nintedanib reduced the decline in forced vital capacity (FVC). The impact of the anti-angiogenic activity of nintedanib in fibrotic lung diseases is currently not known.

The aim is to explore the impact of nintedanib on microvascular architecture in a bleomycin-induced pulmonary fibrosis model.

Effect of Nintedanib on Cytokine/Chemokine Release from Alveolar Macrophages (AMs) in Interstitial Lung Diseases (ILDs): Preliminary Results
[Publication Number: A4396]

X. Long, MD., X. He, MD, D. Theegarten, MD, T.E. Wessendorf, MD, J. Guzman, MD, U. Costabel, MD, F. Bonella, MD. Essen/DE, Bochum/DE.

Am J Respir Crit Care Med 191;2015:A4396.

Nintedanib, a tyrosin kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF), exhibits antifibrotic and antiinflammatory activity. The aim of this study is to evaluate the effect of nintedanib on cytokine/chemokine production by AMs in ILDs.

The Effect of Nintedanib Compared to Pirfenidone on Serum-Stimulated Proliferation of Human Primary Lung Fibroblasts at Clinically Relevant Concentrations
[Publication Number: A4940]

L. Wollin, PhD, J. Schuett, MSc, A. Ostermann, MSc. Biberach/DE. 

Am J Respir Crit Care Med 191;2015:A4940.

Idiopathic pulmonary fibrosis (IPF) is a progressive, severely debilitating disease with a high mortality rate. Nintedanib is an inhibitor of tyrosine kinases targeting also platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor. In contrast the molecular target of pirfenidone is currently unknown. Lung fibroblast proliferation is accepted as a fundamental mechanism involved in the pathogenesis in IPF.Nintedanib and pirfenidone were recently approved by the FDA for the treatment of IPF.

The aim is to determine the effect of nintedanib and pirfenidone on the proliferation rate of serum-stimulated primary human lung fibroblasts.

 

Actualizado el 04/06/2015
FPI.0022.062015

Última actualización 24/11/2017
Uso de cookies
Esta página Web utiliza Cookies propias y de terceros para mejorar nuestros servicios y analizar los hábitos de navegación del usuario. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración de cookies u obtener más información visitando nuestra Política de Cookies.