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.

Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme

“…In addition to clinical research using existing therapies, novel pharmacotherapies are in development [125]. As nintedanib and pirfenidone are now considered standard of care in IPF, several trials of novel therapeutics (including GLPG1690 [126], PRM-151 [127], PBI-4050 [128] and pamrevlumab [129]) allowed concomitant therapy with nintedanib or pirfenidone in both treatment and placebo arms [125][126][127][128][129]. During a Phase II trial of PBI-4050, an inhibitor of differentiation of fibroblasts into myofibroblasts, an apparent interaction with pirfenidone was observed.…”

Guías chilenas de fibrosis pulmonar idiopática, 2019

“…13,14 y posteriormente grandes ensayos multinacionales, dieron la gran noticia: contábamos con medicamentos que, cumpliendo todas las condiciones que exige la evidencia en medicina, eran eficaces en cambiar el curso de la enfermedad enlenteciendo el avance de la misma y permitiendo ganar años de vida a una mayoría importante de pacientes. Lo más notable es que casi simultáneamente aparecieron la Pirfenidona 15,16 y el Nintedanib 17 , dos antifibróticos diferentes, ambos eficaces, y se ha abierto una gama de nuevas moléculas que se están probando y seguramente en los próximos años dispondremos de nuevas drogas útiles 18 .…”

Versatile workflow for cell type resolved transcriptional and epigenetic profiles from cryopreserved human lung

“…Chronic obstructive pulmonary disease 4 (COPD) and idiopathic pulmonary fibrosis 5 (IPF) are devastating lung diseases characterized by progressive airflow limitation and tissue scarring, respectively. To date, limited therapeutic options are available for COPD and IPF, thus, major efforts are made in both academic labs and pharmaceutical industries 4,6,7 to identify novel drugs targeting key molecular pathways involved in the pathogenesis of these diseases.…”