Asri Lecture Hall: Efficacy analysis of pirfenidone in IPF patients with defined and undefined UIP

【Introduction to Aisra】

Normal interstitial pneumonia (UIP) is a pathological type
of interstitial pneumonia.
Chest x-ray of UIP patients is mainly manifested by a reticular shadow on the base and periphery of both lungs, often bilateral, asymmetrical, with decreased lung volume; CT and HRCT are characterized by two lung flaks, basal-dominated reticular shadows, with a small amount of ground glass opacities, severe cases of fibrosis, and often traction bronchial and bronchiectasis and/or subpleural cellular-like changes
.

HRCT in patients with IPF usually presents as ordinary interstitial pneumonia (UIP), however some patients may be diagnosed with IPF but their HRCT does not show a clear UIP, i.
e.
, a patient with
a probable/suspicious UIP type of IPF diagnosed by an imaging department.
So is there a difference between the effectiveness of these IPF patients who cannot be diagnosed with UIP taking pirfenidone and those who can diagnose IPF with PIFENIDONE (the drug represented by Asri as the main representative)?

【Research Progress】

In September, a study published in PLOS ONE by a team of experts from multiple countries used data from multi-national European MultiPartner IPF Registry (EMPIRE) to review and analyze the treatment benefits of pirfenidone for patients with different types of IPF
.

【Patient Situation】

The study included patients with IPF who completed EMPIRE registration and followed up to October 29, 2019 from January 1, 2015 to December 31, 2018, all of whom underwent HRCT and lung biopsy for histopathological evaluation and MDT discussion to make a final IPF diagnosis
.
At the same time, the EMPIRE data also included patients whose HRCT or histopathological results did not show UIP patterns
.
In the end, a total of 1626 patients with IPF were included, of which 808 received pirfenidone (pirfenidone group) and 818 did not receive antifibrotic therapy (non-antifibrotic treatment group
).

【Comparison of efficacy】

Pifenidone therapy can benefit
patients with IPF of both UIP type and possibly UIP type.
Patients receiving pirfenidone had higher
OS rates compared to patients who did not receive anti-fibrotic therapy.
(The OS rate is considered the best efficacy endpoint in a tumor clinical trial and is the preferred endpoint when the patient's survival can be adequately assessed.
)

As shown in the figure above, the survival rate of pirfenidone group vs the group without anti-fibrosis therapy was 87.
1% vs.
79.
8% after 1 year of follow-up, 72.
8% vs 63.
2% after 2 years of follow-up, and 57.
9% vs 55.
6% after 3 years of follow-up.

As shown in the figure above, the survival rates after relapse (PRS), pirfenidone group vs.
non-antifibrotic therapy group were 59.
7% vs 53.
6% after follow-up, 30.
9% vs 28.
1% after follow-up, and 15.
8% vs 14.
5% after 3 years of follow-up.
The median time to IPF progression was 15.
3 months and 13.
9 months, respectively
, in the pirfenidone group and the group without antifibrosis therapy.

As shown in the figure above, the overall survival rate was higher in all subgroups classified by diagnostic certainty, including IPF patients with a definitive diagnosis of UIP and patients with IPF who were not clearly diagnosed with
UIP.

As shown in the figure above, the FVC of the pifenidone group vs the group without antifibrotic therapy, and the FVC of the pirfenidone group decreased to -0.
073 L/year (95% CI, -0.
230 to -0.
109 L/year); FVC in the group without antifibrotic therapy decreased to -0.
209 L/year (95% CI: -0.
289 to -0.
130 L/year; P=0.
011）
。

Pifenidone also has a significant delaying effect on the decline in lung function in patients with confirmed IPF but not clearly manifested as UIP, pifenidone group -0.
073 liters / year (95% CI: -0.
132 liters / to -0.
015 liters / year); Group without antifibrotic therapy - 0.
193 L/year (95% CI: -0.
272 L/year to -0.
114 L/year);

This suggests that PIFENIDONE can slow the decline in lung function regardless of whether HRCT in patients with IPF presents with or without a UIP type, but that pirfenidone may be more
effective in patients with definite UIP/IPF.

【Research Conclusion】

In summary, analysis of real-world data from EMPIRE registry studies confirmed that pyrifenidone (the primary agent represented by Asri) treatment prolongs progression-free survival and slows deterioration
of lung function in patients with IPF with and unspecified UIP manifestations of HRCT.
That is, patients with IPF, regardless of whether HRCT has a clear UIP manifestation, such as CTD-ILD, hypersensitivity pneumonia, etc.
may benefit
from pirfenidone.

【References】

LI Xia, LI Huiping, HE Guojun, .
Comparative analysis of the characteristics and prognosis of idiopathic nonspecific interstitial pneumonia and ordinary interstitial pneumonia[J].
International Journal of Respiration, 2008, 28(20):4.

Májek O, Gregor J, Mogulkoć N, et al.
Survival and lung function decline in patients with definite, probable and possible idiopathic pulmonary fibrosis treated with pirfenidone[J].
PloS one, 2022, 17(9): e0273854.