title: Pharmacological treatment of idiopathic pulmonary fibrosis - preclinical and clinical studies of pirfenidone, nintedanib, and N-acetylcysteine.
abstract: Three recent clinical trials on the pharmacologic treatment of idiopathic pulmonary fibrosis (IPF) mark a new chapter in the management of patients suffering from this very severe fibrotic lung disease. This review article summarizes the published investigations on the preclinical studies of three novel IPF drugs, namely pirfenidone, nintedanib, and N-acetylcysteine (NAC). In addition, the study protocols, differences, and the main findings in the recent clinical trials of these pharmacological treatments are reviewed. The strategy for drug development and the timeline from the discovery to the clinical use have been very different in these regimens. Pirfenidone was discovered in 1976 but only recently received approval in most countries, and even now its exact mechanism of action is unknown. On the contrary, nintedanib (BIBF1120) was identified in large drug screening tests as a very specific inhibitor of certain tyrosine kinases, but no published data on preclinical tests existed until 2014. NAC, a mucolytic drug with an antioxidant mechanism of action was claimed to possess distinct antifibrotic properties in several experimental models but proved to be ineffective in a recent randomized placebo-controlled trial. At present, no curative treatment is available for IPF. A better understanding of the molecular mechanisms of IPF as well as relevant preclinical tests including animal models and in vitro experiments on human lung cells are needed to promote the development of therapeutic drugs.
authors.affiliation: Department of Pulmonary Medicine, Helsinki University Central Hospital, Heart and Lung Center and the University of Helsinki, Helsinki, Finland.
authors.forename: Marjukka
authors.initials: M
authors.lastname: Myllärniemi
authors.affiliation: Department of Internal Medicine, Respiratory Diseases, Institute of Clinical Medicine, University of Oulu, Oulu, Finland ; Medical Research Center Oulu, Respiratory Research Unit, Oulu University Hospital, Oulu, Finland ; Unit of Medicine and Clinical Research, Pulmonary Division, University of Eastern Finland, Kuopio, Finland ; Division of Respiratory Medicine, Center for Medicine and Clinical Research, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Kaarteenaho
keywords: Idiopathic pulmonary fibrosis; nintedanib; pirfenidone