Current and novel drug therapies for idiopathic pulmonary fibrosis

Abstract

Over the past decade, there has been a cohesive effort from patients, physicians, clinical and basic scientists, and the pharmaceutical industry to find definitive treatments for idiopathic pulmonary fibrosis (IPF). As understanding of disease behavior and pathogenesis has improved, the aims of those treating IPF have shifted from reversing the disease to slowing or preventing progression of this chronic fibrotic illness. It is to be hoped that by slowing disease progression, survival will be improved from the current dismal median of 3.5 years following diagnosis. In Europe and Asia, a milestone has recently been reached with the licensing of the first IPF-specific drug, pirfenidone. This review assesses the current treatment modalities available for IPF, including pirfenidone. It also turns an eye to the future and discusses the growing number of promising compounds currently in development that it is hoped, in time, will make their way into the clinic as treatments for IPF.

Keywords: acute exacerbations; clinical trials; interstitial lung disease; pirfenidone; usual interstitial pneumonia.

Figure 1

Current understanding of the pathogenesis of idiopathic pulmonary fibrosis (IPF) suggests that repetitive alveolar epithelial injury results in basement membrane denudation and activation of key pathways involved in the wound-healing response. Notes: This in turn leads to fibroblast proliferation, transformation of fibroblasts to myofibroblasts, and expansion of the extracellular matrix. These effects are augmented by the influx of circulating inflammatory cells, including the putative bone marrow–derived fibroblast precursor – the fibrocyte. Various treatments are in development targeting different aspects of IPF disease pathogenesis through inhibition of fibrogenesis, promotion of antifibrotic pathways, or reduction of alveolar injury. Copyright^© 2012. Reprinted with permission from Elsevier. Maher TM. Idiopathic pulmonary fibrosis: pathobiology of novel approaches to treatment. Clin Chest Med. 2012;33:69–83. Abbreviations: FXa, factor Xa; PAR, protease-activated receptor; HGF, hepatocyte growth factor; KGF, keratinocyte growth factor; IL, interleukin; TGF, transforming growth factor; CTGF, connective tissue growth factor; VEGF, vascular endothelial growth factor; NOX4, NADPH Oxidase 4. EP, E prostanoid; LPA, Lysophosphatidic acid; CCL-2, Chemokine (C-C motif) ligand 2.