Pirfenidone and Nintedanib for Treatment of Idiopathic Pulmonary Fibrosis

Gayathri Sathiyamoorthy, MD; Sameep Sehgal, MD; Rendell W. Ashton, MD

Disclosures

South Med J. 2017;110(6):393-398. 

In This Article

Abstract and Introduction

Abstract

Idiopathic pulmonary fibrosis is one of the most common entities of the family of disorders known as the interstitial lung diseases. It is a chronic, progressive, and often-fatal disease with a median survival time of 3 to 5 years. In 2014 the US Food and Drug Administration approved pirfenidone and nintedanib, two antifibrotic agents for the treatment of idiopathic pulmonary fibrosis. Because these are the only drugs approved that can alter the course of this rare but fatal disease, this article reviews the major studies that led to the approval of these drugs and examines the indications for treatment and the expected outcomes of therapy.

Introduction

The idiopathic interstitial pneumonias are a subset of interstitial lung diseases (ILD) with unknown etiology that are classified based on specific radiologic and histologic patterns. Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of idiopathic interstitial pneumonia. On high-resolution computed tomography of the chest, subpleural and basal distributions of reticular abnormalities and honeycombing with or without traction bronchiectasis are typically seen (Figs. 1 and 2), and a classic radiographic appearance usually is sufficient to make the diagnosis. If atypical features are present on high-resolution computed tomography, then the diagnosis may not be definite but labeled probable or possible IPF. Surgical lung biopsy may then be required to confirm the diagnosis. The histologic pattern known as usual interstitial pneumonia consists of marked fibrosis, architectural distortion with geographic and temporal heterogeneity, and honeycombing changes predominantly in the subpleural and paraseptal distributions. Patchy involvement of lung parenchyma by fibrosis and fibroblastic foci are seen typically (Figs. 3–5).[1] The disease process is limited to the lung and usually occurs in patients 60 years old and older. It is associated with a poor prognosis, although disease progression can be variable and often is unpredictable. In the United States, IPF prevalence is estimated to be at 14 to 43/100,000 individuals[2] and the median survival time is approximately 3 to 5 years from time of diagnosis[3] (Table 1). Because of the prevalence and high mortality of IPF, researchers have studied a wide variety of potential agents, searching for an effective treatment. Until 2014, the story of treatment for IPF was one of dismal failure, featuring various drugs and combination therapies, which showed initial promise theoretically or when tested in vitro, but only produced adverse effects with no benefit when studied in clinical trials. With this background in mind, it is easy to understand the excitement as well as the skepticism within the ILD community when two randomized controlled trials published in 2014 promised some efficacy in treating IPF. The two antifibrotic agents studied in these trials are pirfenidone and nintedanib, which were approved in 2014 by the US Food and Drug Administration (FDA) for the treatment of IPF. Patients with IPF and the providers who care for them have undergone a long wait for effective therapy and now have the option of two drugs with potential benefits. In light of the current era of extensive marketing by manufacturers and heavy media coverage surrounding any therapeutic breakthroughs such as this one, we aim to objectively evaluate the existing literature regarding these FDA approved treatment options. We review here the major studies that led to the approval of pirfenidone and nintedanib, discuss what is known of their mechanism of action and clinical features, and offer recommendations for the care of patients with IPF who may desire referral for consideration of either of these medications.

Figure 1.

Computed tomography, axial view (lung window) showing subpleural reticular opacities and peripheral honeycomb change (blue arrow). Radiology figures courtesy of Ruchi Yadav, MD.

Figure 2.

Computed tomography, coronal view (lung window) demonstrating basilar predominance of reticular opacities and honeycomb change.

Figure 3.

Usual interstitial pneumonia: temporal heterogeneity. Scarred lung (green arrow) is abruptly juxtaposed to normal lung (blue arrow) (200x, H&E). Pathology figures courtesy of Sanjay Mukhopadhyay, MD.

Figure 4.

Usual interstitial pneumonia: microscopic honeycomb change. Dilated, mucin-filled spaces lined by respiratory epithelium (green arrow) (40x, H&E).

Figure 5.

Usual interstitial pneumonia: fibroblast focus. Note localized collection of fibroblasts within the interstitium (green arrows) (200x, H&E).

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