An updated safety review of the drug treatments for idiopathic pulmonary fibrosis

ABSTRACT

Introduction

The approval of antifibrotic agents nintedanib and pirfenidone revolutionized the management of idiopathic pulmonary fibrosis (IPF). These treatments showed acceptable tolerability in randomized-clinical trials; however, they have been associated with a spectrum of potential side effects which require careful assessment of risks and benefits in the individual patient before commencing and during antifibrotic therapy.

Areas covered

The accrued evidence on safety of nintedanib and pirfenidone is summarized, from the first randomized clinical trials to the open-label extension studies and post-marketing clinical experiences which helped clarify the long-term tolerability of these drugs.

Expert opinion

The data collected over the last years confirmed the comparable tolerability profile of nintedanib and pirfenidone. The physician’s assessment of expected side effects may help decide the optimal first-line therapy for the individual patient. Patient’s counseling during treatment remains essential to manage emerging adverse events and eventually inform the decision of drug discontinuation.

KEYWORDS:

• Idiopathic pulmonary fibrosis
• pirfenidone
• nintedanib
• safety
• tolerability

Article highlights

• Nintedanib and pirfenidone have transformed the management of idiopathic pulmonary fibrosis, as they are capable of slowing down the decline of pulmonary function in these patients.

• The data collected over the last years from extension studies of clinical trials and real-life reports largely confirmed the tolerability profile of the two antifibrotic drugs, with no new emerging safety signals.

• Drug discontinuation still occurs in a considerable proportion of patients treated with antifibrotics, more frequently in those with more advanced disease and significant comorbidities.

• The choice of nintedanib or pirfenidone as first-line drug should be based on their tolerability profile, the expected side effects in the individual patient and on his/her personal preferences.

• Patients commencing treatment with pirfenidone or nintedanib should be carefully followed up in order to manage adverse events and therefore reduce the risk of premature discontinuation.

This box summarizes key points contained in the article.

Declaration of interest

G Sgalla reports personal fees from Boehringer Ingehleim, outside the submitted work. L Richeldi reports personal fees and other from Boehringer Ingelheim, other from Fibrogen, personal fees from InterMune, personal fees from Cipla, personal fees from Vertex, other from GlaxoSmithKline, other from Astrazeneca, other from Sanofi-Aventis, other from Celgene, other from Prometic, other from Roche, from Takeda, outside the submitted work. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have received personal fees from Boehringer Ingelheim Japan. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.