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Elizabeth F Redente, Martin A Aguilar, Bart P Black, Benjamin Edelman, Ali Bahadur, Stephen M Humphries, David A Lynch, Lutz Wollin, David W H Riches
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) develops in approximately 20% of patients with RA. SKG mice, which are genetically prone to developing autoimmune arthritis, develop a pulmonary interstitial pneumonia that resembles human cellular and fibrotic non-specific interstitial pneumonia. Nintedanib, a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis, has been shown to reduce lung function decline. Therefore, we investigated the effect of nintedanib on the development of pulmonary fibrosis and joint disease in female SKG mice with arthritis induced by intraperitoneal injection of zymosan (5 mg)...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Gali Epstein Shochet, Lutz Wollin, David Shitrit
BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. Activated fibroblasts are the key effector cells in fibrosis, producing excessive amounts of collagen and extracellular matrix (ECM) proteins. Whether the ECM conditioned by IPF fibroblasts determines the phenotype of naïve fibroblasts is difficult to explore. METHODS: IPF-derived primary fibroblasts were cultured on Matrigel and then cleared using ammonium hydroxide, creating an IPF-conditioned matrix (CM)...
March 12, 2018: Respirology: Official Journal of the Asian Pacific Society of Respirology
Doreen Luedtke, Kristell Marzin, Arvid Jungnik, Ute von Wangenheim, Claudia Dallinger
BACKGROUND: Nintedanib is a substrate for p-glycoprotein which can impact bioavailability. We investigated the effects of ketoconazole, a p-glycoprotein inhibitor, and rifampicin, a p-glycoprotein inducer, on the pharmacokinetics of nintedanib. METHODS: In the ketoconazole study, 34 healthy subjects received nintedanib 50 mg orally alone and 1 h after the last dose of ketoconazole given orally at a dose of 400 mg once daily for 3 days in 1 of 2 randomized sequences...
March 2, 2018: European Journal of Drug Metabolism and Pharmacokinetics
Eva Brunnemer, Julia Wälscher, Svenja Tenenbaum, Julia Hausmanns, Karen Schulze, Marianne Seiter, Claus Peter Heussel, Arne Warth, Felix J F Herth, Michael Kreuter
BACKGROUND: Nintedanib, an oral tyrosine kinase inhibitor, has been shown to slow down the progression of idiopathic pulmonary fibrosis (IPF) in two randomised placebo-controlled trials by reducing the annual decline in forced vital capacity (FVC). However, real-world experience is limited. OBJECTIVE: To assess the efficacy and safety of nintedanib in a large cohort of patients treated at a tertiary referral site for interstitial lung diseases. METHODS: The records of patients with a confirmed diagnosis of IPF were reviewed...
February 28, 2018: Respiration; International Review of Thoracic Diseases
Giacomo Sgalla, Bruno Iovene, Mariarosaria Calvello, Margherita Ori, Francesco Varone, Luca Richeldi
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease characterized by the aberrant accumulation of fibrotic tissue in the lungs parenchyma, associated with significant morbidity and poor prognosis. This review will present the substantial advances achieved in the understanding of IPF pathogenesis and in the therapeutic options that can be offered to patients, and will address the issues regarding diagnosis and management that are still open. MAIN BODY: Over the last two decades much has been clarified about the pathogenic pathways underlying the development and progression of the lung scarring in IPF...
February 22, 2018: Respiratory Research
Michelle Vega-Olivo, Gerard J Criner
Idiopathic pulmonary fibrosis (IPF) is a rare disease characterized by decline in lung function, dyspnea, and cough. The clinical course of IPF is variable and unpredictable. Early referral to specialists is key to ensure timely and accurate diagnosis. Two antifibrotic drugs (nintedanib and pirfenidone) have been approved for the treatment of IPF.
February 19, 2018: Nurse Practitioner
Philippe Lachapelle, Meina Li, Jo Douglass, Alastair Stewart
The transforming growth factor (TGF)-β cytokines play a central role in development and progression of chronic respiratory diseases. TGF-β overexpression in chronic inflammation, remodeling, fibrotic process and susceptibility to viral infection is established in the most prevalent chronic respiratory diseases including asthma, COPD, lung cancer and idiopathic pulmonary fibrosis. Despite the overwhelming burden of respiratory diseases in the world, new pharmacological therapies have been limited in impact...
February 17, 2018: Pharmacology & Therapeutics
Binyan Lin, Xiuming Song, Dawei Yang, Dongsheng Bai, Yuyuan Yao, Na Lu
Tumor cells recruit vascular endothelial cells and circulating endothelial progenitor cells to form new vessels to support their own growth and metastasis. VEGF, PDGF-BB and FGF-2 are three major pro-angiogenic factors and applied to promote angiogenesis. In this research, we demonstrated that anlotinib, a potent multi-tyrosine kinases inhibitor (TKI), showed a significant inhibitory effect on VEGF/PDGF-BB/FGF-2-induced angiogenesis in vitro and in vivo. Wound healing assay, chamber directional migration assay and tube formation assay indicated that anlotinib inhibited VEGF/PDGF-BB/FGF-2-induced cell migration and formation of capillary-like tubes in endothelial cells...
February 14, 2018: Gene
Letícia Ferreira Alves, Raquel Frenedoso da Silva, Valéria Helena Alves Cagnon
Prostate cancer is the most prevalent type of cancer in men around the world. Due to its high incidence, new therapies have been evaluated, including drugs capable of inhibiting the FGF/VEGF pathways, as Nintedanib. The aim herein was to evaluate the Nintedanib therapeutic effects on morphology and COX-2 and IL-17 levels in the prostate anterior lobe in different grades of the tumor progression in TRAMP mice. Animals were treated with Nintedanib at a dose of 10 mg/kg/day in initial and intermediate grades of tumor development...
February 2018: Tissue & Cell
Michael Kreuter, Ulrich Costabel, Luca Richeldi, Vincent Cottin, Marlies Wijsenbeek, Francesco Bonella, Elisabeth Bendstrup, Toby M Maher, Daniel Wachtlin, Susanne Stowasser, Martin Kolb
BACKGROUND: Cardiovascular comorbidities are frequent in patients with idiopathic pulmonary fibrosis (IPF), and many patients with IPF receive treatment with statins to reduce cardiovascular risk. OBJECTIVES: We investigated whether statin use at baseline was associated with differences in disease progression in placebo-treated patients or influenced the treatment effect of nintedanib in the INPULSIS® trials. METHODS: Post-hoc subgroup analyses of patients receiving versus not receiving statins at baseline using pooled data from the INPULSIS® trials...
February 7, 2018: Respiration; International Review of Thoracic Diseases
Fanny Porte, Vincent Cottin, Laura Catella, Laura Luciani, Katell Le Lay, Stève Bénard
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause. To date, there is no specific cure for IPF and only two treatments (pirfenidone and nintedanib) have marketing authorizations and recommendations in international and French guidelines. OBJECTIVES: A cost-utility analysis (CUA) has been conducted to evaluate the efficiency of nintedanib, in comparison to all available alternatives, in a French setting using the official methodological guidelines...
January 25, 2018: Current Medical Research and Opinion
Argyrios Tzouvelekis, Theodoros Karampitsakos, Maria Kontou, Andreas Granitsas, Ioanna Malliou, Aris Anagnostopoulos, Paschalis Ntolios, Vasilios Tzilas, Evangelos Bouros, Paschalis Steiropoulos, Serafeim Chrysikos, Katerina Dimakou, Nikolaos Koulouris, Demosthenes Bouros
BACKGROUND: Nintedanib represents an antifibrotic compound able to slow down disease progression of patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To investigate the safety and efficacy of nintedanib in patients with IPF in a real-life setting. METHODS: This was a multicentre, retrospective, observational, real-life study for patients with IPF receiving nintedanib between October 2014 and October 2016. RESULTS: We identified 94 patients with IPF receiving nintedanib (72 males, mean age±SD: 73...
January 20, 2018: Pulmonary Pharmacology & Therapeutics
Takashi Nakano
Malignant pleural mesothelioma(MPM)is a highly aggressive tumor with a poor prognosis and an increasing incidence worldwide. The only standard first-line chemotherapy for patients with unresectable MPM is cisplatin(CDDP)plus peme- trexed(PEM)(CDDP/PEM), with a median overall survival of about 12months and a median progression-free survival(PFS) of less than 6 months. There are no treatments with proven benefit on survival for relapsed MPM patients. Therefore, novel therapeutic strategies are urgently required...
December 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Jürgen Behr, Andreas Günther, Francesco Bonella, Klaus Geißler, Dirk Koschel, Michael Kreuter, Antje Prasse, Nicolas Schönfeld, Helmut Sitter, Joachim Müller-Quernheim, Ulrich Costabel
Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a median survival of 2 - 4 years after diagnosis. Since the publication of the German IPF guideline in 2013 new treatment trials have been published, necessitating an update of the pharmacological therapy of IPF. Different from the previous guideline, the GRADE system was discarded and replaced by the Oxford evidence classification system which allows a more differentiated judgement. The following pharmacological therapies were rated not suitable for the treatment of IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone, azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan...
January 16, 2018: Pneumologie
Francesco Varone, Giacomo Sgalla, Bruno Iovene, Teresa Bruni, Luca Richeldi
Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease characterized by the progressive loss of pulmonary function, ultimately leading to respiratory failure and death. Two novel compounds, nintedanib and pirfenidone, have shown efficacy in reducing the rate of decline of lung function in IPF patients. The multiple tyrosine kinase inhibitor nintedanib has extensively being studied as a potential angiogenesis inhibitor in clinical against various neoplastic disorders. Afterwards, this compound was successfully tested in IPF...
February 2018: Expert Opinion on Pharmacotherapy
Wan Shun Daniel Tan, Wupeng Liao, Shuo Zhou, Dan Mei, Wai-Shiu Fred Wong
The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects. Novel intervention is definitely needed to offer optimal therapeutic strategy and clinical outcome...
December 27, 2017: Current Opinion in Pharmacology
Cheng Chen, Yong-Yan Wang, Ying-Xia Wang, Meng-Qun Cheng, Jian-Bing Yin, Xuan Zhang, Zhi-Peng Hong
Pulmonary fibrosis (PF) is a chronic and ultimately fatal interstitial lung disease of various causes. The advent of nintedanib and pirfenidone provides treatment options for PF patients for the first time. However, the adverse effects of the two drugs such as gastrointestinal disorders and hepatic dysfunction often lead to treatment discontinuation. Gentiopicroside (GPS) is a natural secoiridoid glycoside from gentian species of medicinal plants, and has a variety of pharmacological activities, including hepatoprotective and cholagogic, anti-inflammatory, antinociceptive, and smooth muscle relaxing activities...
December 23, 2017: Biochemical and Biophysical Research Communications
Satoshi Okamori, Takanori Asakura, Keita Masuzawa, Hiroyuki Yasuda, Hirofumi Kamata, Makoto Ishii, Tomoko Betsuyaku
RATIONAL: The efficacy of nintedanib, a multitarget receptor tyrosine kinase inhibitor, has been demonstrated in recent randomized controlled trials involving patients with idiopathic pulmonary fibrosis (IPF). However, accelerated disease progression after nintedanib discontinuation has never been reported. PATIENT CONCERNS: We report 2 cases involving patients with a history of IPF who presented with respiratory deterioration at 3 weeks after the discontinuation of nintedanib therapy for IPF...
December 2017: Medicine (Baltimore)
Chiara Scelfo, Antonella Caminati, Sergio Harari
Idiopathic pulmonary fibrosis (IPF) is a rare pulmonary disease with a poor prognosis and severe impact on quality of life. Early diagnosis is still challenging and important delays are registered before final diagnosis can be reached. Available tools fail to predict the variable course of the disease and to evaluate response to antifibrotic drugs. Despite the recent approval of pirfenidone and nintedanib, significant challenges remain to improve prognosis and quality of life. It is hoped that the new insights gained in pathobiology in the last few years will lead to further advances in the diagnosis and management of IPF...
2017: F1000Research
José Antonio Rodríguez-Portal
Idiopathic pulmonary fibrosis is a fatal form of progressive fibrosing interstitial pneumonia with limited treatment options. In recent years, its management has been transformed with the approval of two new antifibrotic drugs: nintedanib and pirfenidone. Nintedanib is a tyrosine kinase inhibitor that efficiently slows idiopathic pulmonary fibrosis progression and has an acceptable tolerability profile. This article reviews new available evidence on the long-term efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis...
March 2018: Drugs in R&D
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