Antibody-based therapies for idiopathic pulmonary fibrosis

ABSTRACT

Introduction

Pirfenidone and nintedanib have been the first agents demonstrating to slow down the progressive functional decline in patients with Idiopathic Pulmonary Fibrosis (IPF). Antibody-based therapies with precise molecular targets have been largely investigated over the last decade in IPF as alternative or complementary treatments, in the hope to ameliorate the relentless fibrotic process of IPF.

Areas covered

In this review, we summarize the available evidence on two groups of monoclonal antibodies tested in IPF: those directed against known fibrogenic factors and matrix components, and those developed to antagonize the inflammation and immunity pathways. While the latter have failed to demonstrate any clinical efficacy in IPF so far, the anti-CTGF pamrevlumab has been recently proved to be capable of slowing down functional decline as compared to placebo, prompting further investigation.

Expert opinion

Despite most trials on antibody-based therapies in IPF provided so far unsatisfying results, the therapeutic development in this field should continue to be pursued to deliver a more personalized treatment approach in the future, which is not currently offered by available treatment options. A more careful trial designing and the use of valid predictive markers of response to treatment are required to enhance effectiveness of future trials.

KEYWORDS:

• Idiopathic pulmonary fibrosis
• antibody-based therapy
• interstitial lung disease
• IPF treatment
• randomized clinical trials
• precision medicine

Article highlights

• Nintedanib and pirfenidone, the two currently available treatments for Idiopathic Pulmonary Fibrosis, slow down but do not halt clinical and functional deterioration in these patients.

• Several antibody-based treatments directed against factors involved in either the profibrotic and the inflammation/immunity cascades have been tested in randomized clinical trials (RCTs) over the last decade.

• Most RCTs on antibody-based therapies were not successful in demonstrating efficacy of the experimental drug against placebo.

• Pamrevlumab, an anti-CTGF monoclonal antibody, has been the only proving so far to be effective as compared to placebo in IPF patients, and is being investigated in a phase 3 RCT.

• More accurate disease stratification using predictive markers of response to novel targeted treatments is needed more than ever to increase effectiveness of future RCTs and pave the way to personalized treatment in IPF.

This box summarizes key points contained in the article.

Declaration of interest

G Sgalla reports fees from Boehringer Ingelheim outside the submitted work. L Richeldi has received grants and personal fees from Boehringer Ingelheim and InterMune, and personal fees from Biogen-Idec, ImmuneWorks, Medimmune, Roche, Sanofi-Aventis, Shionogi, and Takeda outside of 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.