The therapy of idiopathic pulmonary fibrosis: what is next?

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease, characterised by progressive scarring of the lung and associated with a high burden of disease and early death. The pathophysiological understanding, clinical diagnostics and therapy of IPF have significantly evolved in recent years. While the recent introduction of the two antifibrotic drugs pirfenidone and nintedanib led to a significant reduction in lung function decline, there is still no cure for IPF; thus, new therapeutic approaches are needed. Currently, several clinical phase I-III trials are focusing on novel therapeutic targets. Furthermore, new approaches in nonpharmacological treatments in palliative care, pulmonary rehabilitation, lung transplantation, management of comorbidities and acute exacerbations aim to improve symptom control and quality of life. Here we summarise new therapeutic attempts and potential future approaches to treat this devastating disease.

FIGURE 1

Evolution of treatment in idiopathic pulmonary fibrosis (IPF). Schematic representation of clinical trials of therapy performed for IPF in the past three decades. Circle sizes are an approximate representation of the sample sizes of the clinical trials. +: study ended with positive outcome; −: study ended with negative outcome. Reproduced and modified from [3] with permission.

FIGURE 2

Graphic expression (comorbidome) of comorbidities with >10% prevalence in the entire cohort, and those comorbidities with the strongest association with mortality (hazard ratio (HR) >1, 95% CI >1; p<0.05) [166]. The area of the circle relates to the prevalence of the disease. The proximity to the centre (mortality) expresses the strength of the association between the disease and risk of death. This was scaled from the inverse of the HR (1/HR). All bubbles associated with a statistically significant increase in mortality are fully inside the dotted orbit (1/HR <1). Bubble colours represent organ systems or disease clusters. CV: cardiovascular; CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease. Reproduced and modified from [186] with permission.