Pharmacological management of Idiopathic Pulmonary Fibrosis: current and emerging options

ABSTRACT

Introduction

Idiopathic Pulmonary Fibrosis is a chronic, progressive lung disease characterized by worsening lung scarring and the radiological/histological pattern of usual interstitial pneumonia. Substantial progress has been made in the clinical management of IPF in the last decade. The two novel antifibrotics, Nintedanib and Pirfenidone have changed the landscape of IPF, by hindering disease progression; however, the drugs have significant discontinuation rates, due to adverse events and do not offer a definitive cure, as such IPF remains a deleterious disease with poor survival.

Areas covered

In this review, the authors focus on the current and emerging pharmacological options in the treatment of IPF. They include a summary of the current approach including treatment of comorbidities and then discuss promising drugs in the drug pipeline.

Expert opinion

IPF remains a disease with detrimental outcomes. The plethora of emerging pharmacological treatments brings hope for the future. The current pharmacological ‘one fits all’ approach has been proven effective in slowing disease progression. The future lies in an oncological approach with combination of therapies. We expect to see a change in clinical trial endpoints and a more inclusive approach for the diagnosis of IPF.

Abbreviation list

AE: Acute ExacerbationA-SMA: a smooth muscle actinATX: AutotaxinCOPD: Combined Obstructive Pulmonary DiseaseCPFE: Combined Pulmonary Fibrosis and EmphysemaGER: Gastro-esophageal refluxFVC: forced vital capacityECMO: extracorporeal membrane oxygenationILD: Interstitial Lung DiseaseIPF: Idiopathic Pulmonary FibrosisNAC: N-acetylcysteineLPA: Lysophosphatidic acidPH: Pulmonary RehabilitationPR: Pulmonary rehabilitationRCTs: randomized placebo-controlled trialsUIP: usual interstitial pneumonia

KEYWORDS:

• IPF
• current
• emerging
• pharmacotherapy
• drugs

Article highlights

• IPF is a devastating disease

• Antifibrotics (Nintedanib and Pirfenidone) are breakthrough treatments that have improved the progression of the disease

• Antifibrotics are largely considered ’dirty drugs’ acting on multiple fibrotic pathways

• The future would involve the use of a highly pleiotropic agent along with a pathway-specific novel therapy, based on molecular phenotyping

• Clinical trials will need reflect the real-life clinical practice, by adopting the more inclusive ‘working diagnosis’ of IPF

• Clinical Trials endpoints will probably sift to composite endpoints using time to clinical worsening and molecular biomarkers

This box summarizes key points contained in the article.

Declaration of interest

AU Wells discloses personal fees for consultancy and/or speaking roles from Actelion, Boehringer Ingelheim, Roche, and Bayer. The authors have no other 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 apart from those disclosed

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.