Absence of early metabolic response assessed by 18F-FDG PET/CT after initiation of antifibrotic drugs in IPF patients

Respir Res. 2019 Jan 15;20(1):10. doi: 10.1186/s12931-019-0974-5.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a progressive and irreversible respiratory failure. Non-invasive markers of disease activity are essential for prognosis and evaluation of early response to anti-fibrotic treatments.

Objectives: The aims of this study were to determine whether fluorodeoxyglucose ([18F]-FDG) lung uptake is reduced after initiation of pirfenidone or nintedanib and to assess its possible use as a prognostic factor.

Methods: [18F]-FDG PET/CT was performed in IPF patients and in a murine model of pulmonary fibrosis. PET/CTs were performed at day 8 and day 15 post-instillation of bleomycin in pirfenidone- or vehicule-treated mice. In IPF patients, PET-CT was performed before and 3 months after the initiation of pirfenidone or nintedanib.

Results: In bleomycin-treated mice, pirfenidone significantly reduced the [18F]-FDG uptake compared to vehicule-treated mice at day 15 (p < 0.001), whereas no difference was observed at day 8 after bleomycin administration. In IPF patients, [18F]-FDG lung uptake before and after 3 months of treatment by nintedanib (n = 11) or pirfenidone (n = 14) showed no significant difference regardless the antifibrotic treatment. Moreover, no difference was noticed between patients with progressive or non-progressive disease at one year of follow up.

Conclusions: Pirfenidone significantly reduces the lung [18F]-FDG uptake during the fibrotic phase in a mouse model of IPF. However, these preclinical data were not confirmed in IPF patients 3 months after the initiation of antifibrotic therapy. [18F]-FDG seems therefore not useful in clinical practice to assess the early response of IPF patients to nintedanib or pirfenidone.

Keywords: Biomarker; ILD; IPF; Idiopathic pulmonary fibrosis; Interstitial lung disease; Nintedanib; PET/CT; Pirfenidone.

MeSH terms

  • Aged
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Female
  • Fibrosis
  • Fluorodeoxyglucose F18*
  • Humans
  • Idiopathic Pulmonary Fibrosis / diagnostic imaging*
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Indoles / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Positron Emission Tomography Computed Tomography / methods*
  • Prospective Studies
  • Pyridones / therapeutic use*

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyridones
  • Fluorodeoxyglucose F18
  • pirfenidone
  • nintedanib