28
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Nintedanib for Systemic Sclerosis–Associated Interstitial Lung Disease

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD.

          Related collections

          Most cited references19

          • Record: found
          • Abstract: found
          • Article: not found

          Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis.

          Idiopathic pulmonary fibrosis is a progressive lung disease with a high mortality rate. Because the signaling pathways activated by several tyrosine kinase receptors have been shown to be involved in lung fibrosis, it has been suggested that the inhibition of these receptors may slow the progression of idiopathic pulmonary fibrosis. In a 12-month, phase 2 trial, we assessed the efficacy and safety of four different oral doses of the tyrosine kinase inhibitor BIBF 1120 as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Secondary end points included acute exacerbations, quality of life (measured with the St. George's Respiratory Questionnaire [SGRQ]), and total lung capacity. A total of 432 patients underwent randomization to receive one of four doses of BIBF 1120 (50 mg once a day, 50 mg twice a day, 100 mg twice a day, or 150 mg twice a day) or placebo. In the group receiving 150 mg of BIBF 1120 twice a day, FVC declined by 0.06 liters per year, as compared with 0.19 liters per year in the placebo group, a 68.4% reduction in the rate of loss with BIBF 1120 (P = 0.06 with the closed testing procedure for multiplicity correction; P = 0.01 with the hierarchical testing procedure). This dose also resulted in a lower incidence of acute exacerbations, as compared with placebo (2.4 vs. 15.7 per 100 patient-years, P = 0.02) and a small decrease in the SGRQ score (assessed on a scale of 0 to 100, with lower scores indicating better quality of life) as compared with an increase with placebo (-0.66 vs. 5.46, P = 0.007). Gastrointestinal symptoms (which led to more discontinuations in the group receiving 150 mg twice a day than in the placebo group) and increases in levels of liver aminotransferases were more frequent in the group receiving 150 mg of BIBF 1120 twice daily than in the placebo group. In patients with idiopathic pulmonary fibrosis, BIBF 1120 at a dose of 150 mg twice daily, as compared with placebo, was associated with a trend toward a reduction in the decline in lung function, with fewer acute exacerbations and preserved quality of life. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00514683 .).
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis

            Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease characterised by fibrosis of the lung parenchyma and loss of lung function. Although the pathogenic pathways involved in IPF have not been fully elucidated, IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair, in which there is uncontrolled proliferation of lung fibroblasts and differentiation of fibroblasts into myofibroblasts, which excessively deposit extracellular matrix (ECM) proteins in the interstitial space. A number of profibrotic mediators including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and transforming growth factor-β are believed to play important roles in the pathogenesis of IPF. Nintedanib is a potent small molecule inhibitor of the receptor tyrosine kinases PDGF receptor, FGF receptor and vascular endothelial growth factor receptor. Data from in vitro studies have shown that nintedanib interferes with processes active in fibrosis such as fibroblast proliferation, migration and differentiation, and the secretion of ECM. In addition, nintedanib has shown consistent anti-fibrotic and anti-inflammatory activity in animal models of lung fibrosis. These data provide a strong rationale for the clinical efficacy of nintedanib in patients with IPF, which has recently been demonstrated in phase III clinical trials.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Mapping and predicting mortality from systemic sclerosis

                Bookmark

                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                Massachusetts Medical Society
                0028-4793
                1533-4406
                May 20 2019
                May 20 2019
                Affiliations
                [1 ]From the Department of Rheumatology, University Hospital Zurich, Zurich (O.D.), and Boehringer Ingelheim (Schweiz), Basel (M. Gahlemann) — both in Switzerland; the Respiratory Institute, Cleveland Clinic, Cleveland (K.B.H.); the Departments of Pulmonary Medicine and Oncology (A.A.) and Allergy and Rheumatology (M.K.), Nippon Medical School Graduate School of Medicine, Tokyo; University of Colorado School of Medicine, Aurora (A.F.); the Division of Rheumatology and Clinical Immunogenetics, University of...
                Article
                10.1056/NEJMoa1903076
                31112379
                d511f953-6a67-49db-acbc-c0d564b341a3
                © 2019

                http://www.nejmgroup.org/legal/terms-of-use.htm

                History

                Comments

                Comment on this article