Pharmacotherapy for idiopathic pulmonary fibrosis: current landscape and future potential

Abstract

Over the past two and a half decades, many clinical trials have been designed to determine the safety and efficacy of pharmacotherapy for patients with idiopathic pulmonary fibrosis (IPF). However, so far, only two drugs (pirfenidone and nintedanib) have been found to have an impact on disease progression as defined by reducing the rate of decline in forced vital capacity over a year among IPF patients with mild to moderate impairment in lung function. These two drugs have been approved for treatment of IPF by regulatory agencies and are currently in clinical use worldwide. This article summarises the current landscape of pharmacotherapy for IPF and highlights the prospects and potential of new therapies that are currently being pursued in clinical trials.

FIGURE 1

Concepts in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Schematic representation and investigational therapies for IPF, targeting aberrant responses to injury. The schematic indicates the sequential profibrotic processes implicated in the currently prevailing paradigm of IPF pathogenesis, in which recurrent or persistent injury to the alveolar epithelium is believed to drive aberrant wound-healing responses, resulting in fibrosis rather than repair. Drug candidates evaluated in recently completed or ongoing phase II and III clinical trials in IPF are placed in the context of the profibrotic process(es) they are believed to target. Although fibrosis in IPF appears to predominantly expand the interstitial compartment, the aberrant repair processes driving IPF progression, and the fibrosis they produce, may occur in both the interstitium and the airspaces. For the purposes of figure clarity, the development of fibrosis in the airspaces is depicted in this figure. ^#: the recent clinical trial using simtuzumab failed to demonstrate the therapeutic potential of blocking LOXL2 [25]. NAC: N-acetylcysteine; IL: interleukin; CTGF: connective tissue growth factor; LOXL2: lysyl oxidase 2. Courtesy of Dr A. Tager; reproduced and modified from [27] with permission from the publisher.