New treatment and markers of prognosis for idiopathic pulmonary fibrosis: lessons learned from translational research

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with increasing prevalence, high mortality rates and poor treatment options. The diagnostic process is complex and often requires an interdisciplinary approach between different specialists. Information gained over the past 10 years of intense research resulted in improved diagnostic algorithms, a better understanding of the underlying pathogenesis and the development of new therapeutic options. Specifically, the change from the traditional concept that viewed IPF as a chronic inflammatory disorder to the current belief that is primarily resulting from aberrant wound healing enabled the identification of novel treatment targets. This increased the clinical trial activity dramatically and resulted in the approval of the first IPF-specific therapy in many countries. Still, the natural history and intrinsic behavior of IPF are very difficult to predict. There is an urgent need for new therapies and also for development and validation of prognostic markers that predict disease progression, survival and also response to antifibrotic drugs. This review provides an up to date summary of the most relevant clinical trials, novel therapeutic drug targets and outlines a spectrum of potential prognostic biomarkers for IPF.

Keywords::

• biomarkers
• clinical trials
• idiopathic pulmonary fibrosis
• prognostic markers

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Idiopathic pulmonary fibrosis (IPF) is a very severe form of chronic lung disease associated with mortality rates that are worse than most cancers – this and the lack of efficacious therapies highlight the need for developing new medicines for IPF.

• • The last decade has seen a dramatic increase of clinical investigation in IPF, with more than 6000 patients being enrolled in clinical trials compared to less than 200 in the preceding decade.

• • The pathogenesis of IPF is complex and involves many different pathways, most of them belonging to the area of tissue injury and repair, less to the field of chronic inflammation. Many novel compounds in drug development target these pathways.

• • The first IPF-specific therapy, pirfenidone, has received regulatory approval in many countries in the last few years; several others are currently explored in advanced clinical trials.

• • Both clinical management and clinical trials rely primarily on decline of forced vital capacity to determine disease progression and drug efficacy, but this outcome is far away from being optimal. Biomarkers hold promise to support clinical decision making in the future.