Pirfenidone and Nintedanib in Pulmonary Fibrosis: Lights and Shadows

Abstract

Pirfenidone and Nintedanib are specific drugs used against idiopathic pulmonary fibrosis (IPF) that showed efficacy in non-IPF fibrosing interstitial lung diseases (ILD). Both drugs have side effects that affect patients in different ways and have different levels of severity, making treatment even more challenging for patients and clinicians. The present review aims to assess the effectiveness and potential complications of Pirfenidone and Nintedanib treatment regimens across various ILD diseases. A detailed search was performed in relevant articles published between 2018 and 2023 listed in PubMed, UpToDate, Google Scholar, and ResearchGate, supplemented with manual research. The following keywords were searched in the databases in all possible combinations: Nintedanib; Pirfenidone, interstitial lung disease, and idiopathic pulmonary fibrosis. The most widely accepted method for evaluating the progression of ILD is through the decline in forced vital capacity (FVC), as determined by respiratory function tests. Specifically, a decrease in FVC over a 6-12-month period correlates directly with increased mortality rates. Antifibrotic drugs Pirfenidone and Nintedanib have been extensively validated; however, some patients reported several side effects, predominantly gastrointestinal symptoms (such as diarrhea, dyspepsia, and vomiting), as well as photosensitivity and skin rashes, particularly associated with Pirfenidone. In cases where the side effects are extremely severe and are more threatening than the disease itself, the treatment has to be discontinued. However, further research is needed to optimize the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality. Finally, other studies are requested to establish the treatments that can stop ILD progression.

Keywords: Nintedanib; Pirfenidone; forced vital capacity; idiopathic pulmonary fibrosis; interstitial lung disease.

Figure 1

CT lung scan of a 75-year-old male patient at the time of UIP diagnosis at our center, after Pirfenidone was started. The CT scan in boxes (A,B) show traction bronchiectasis (red arrow) and honeycombing areas mainly located at the basal zone (red asterisk). CT images in boxes (C,D) were acquired after 3 years of follow up and specific therapy and show progression in findings already present (red arrow and asterisk) together with septal thickening (yellow square), another UIP radiological feature.

Figure 2

Radiological images of a 72-year-old man with SSC-ILD (A–D). CT scans show the main features of NSIP, which is the most common pattern in patients with systemic sclerosis. In particular, traction bronchiectasis (in the blue square) (C,D), ground glass areas (yellow asterisk) (C,D) with a symmetrical distribution and mainly peripheral and lower lobe involvement, and reticular opacities (green arrow) (A) are noted. The blue arrow also indicates the dilated esophagus (B), another feature observed in patients with systemic sclerosis.