Correlation of response to antifibrotic treatment with adverse events to antifibrotic drugs in IPF patients from the real-world EMPIRE registry

Background: A correlation of adverse events (AE), and the efficacy of EGFR TKIs in lung cancer patients (pts) is known. Similar AE are seen in IPF pts treated with triple TKI nintedanib (N) and pirfenidone (P). Post hoc analysis to assess the correlation between clinically outcomes in IPF pts from the real-world EMPIRE registry and AE to antifibrotics. Methods The analysis was performed 6 months after the initiation of antifibrotics according to AE. Correlation with mortality and progression-free survival-PFS, were assessed by the Kaplan–Meier survival function, correlation with AE by the Cox proportional hazards regression analysis. Results: Out of 1,233 pts, 698 were treated with P and 535 with N; AE were observed in 96 pts (7.8%): dyspepsia in 2.1%, elevated liver enzymes in 1.6%, diarrhoea in 0.7%, nausea in 1.1%, photosensitivity,rash,vomiting in 0.3% each, fatigue in 0.2%. The occurrence of AE correlated with the PFS, for all pts (p= 0.004) and for treated with N (p= 0.015), but not mortality. PFS was significantly better in the group of pts with no AE. Fatigue in all pts (adjusted HR 6.0; 1.5–24.8;p= 0.012), in treated with P(5.0; 1.2–20.5;p= 0.027), nausea in pts with N (6.8;1.6–28.8;p= 0.010) correlated with higher mortality. The effect of AE on PFS were noted in all pts for nausea (2.2; 1.2–3.8; p= 0.006) and rash (4.1;1.5–11.0;p= 0.005); in pts on P for rash (4.2;1.5–11.2;p= 0.005);in pts on N for nausea (3.5;1.6–7.5; p= 0.001). Conclusion: The occurrence of AE correlates with PFS, but not with mortality. The occurrence of individual AE is associated with a poorer prognosis of pts.