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. 2023 May 19;12(10):3564.
doi: 10.3390/jcm12103564.

A Real-World Prognosis in Idiopathic Pulmonary Fibrosis: A Special Reference to the Role of Antifibrotic Agents for the Elderly

Kojiro Honda  1 , Takeshi Saraya  1 , Haruyuki Ishii  1
Affiliations

A Real-World Prognosis in Idiopathic Pulmonary Fibrosis: A Special Reference to the Role of Antifibrotic Agents for the Elderly

Kojiro Honda et al. J Clin Med. .

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of idiopathic interstitial pneumonia, and its prevalence increases with age. In the era of pre-antifibrotic agents, the median survival time of Japanese patients with IPF is 35 months, with a 5-year survival rate in western countries ranging from 20% to 40%. The prevalence of IPF is highest in elderly patients aged ≥75 years; however, the efficacy and safety of long-term use of pirfenidone and/or nintedanib are not fully understood.

Objective: This study aimed to determine the efficacy and safety of the sole use of antifibrotic agents (pirfenidone or nintendanib) for IPF in the elderly.

Method: We retrospectively reviewed patients with IPF who were diagnosed and treated with either pirfenidone or nintedanib in our hospital between 2008 and 2019. We excluded patients with the subsequent use of both antifibrotic agents. We examined the survival probability and frequency of acute exacerbation, with focus on long-term use (≥1 year), elderly patients (≥75 years of age), and disease severity.

Results: We identified 91 patients with IPF (male to female ratio: 63 to 28, age 42 to 90 years). The numbers of patients with disease severity classified by JRS (I/II/III/IV) and GAP stage (I/II/III) were (38/6/17/20) and (39/36/6), respectively. The survival probabilities were comparable between the elderly (n = 46) and non-elderly groups (n = 45, p = 0.877). After the initiation of antifibrotic agents, the cumulative incidence ratio of acute exacerbation of IPF was significantly lower in the early stage (GAP stage I, n = 20) than in the progressive stage of disease (GAP stages II and III, n = 20, p = 0.028). A similar trend was noted in the JRS disease severity classification (I, II vs. III, IV) (n = 27 vs. n = 13, p = 0.072). In the long-term treatment (≥1 year) group (n = 40), the survival probabilities at 2 and 5 years after treatment initiation were 89.0% and 52.4%, respectively, which did not reach the median survival rate.

Conclusions: Even in elderly patients (≥75 years of age), antifibrotic agents demonstrated positive effects on survival probability and the frequency of acute exacerbation. These positive effects would be improved for earlier JRS/GAP stages or long-term use.

Keywords: IPF; acute exacerbation; antifibrotic agents; elderly patients; long-term treatment; survival probability.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Survival probabilities based on the Kaplan–Meier method for all enrolled patients: (A) The median survival time (MST) from the first visit to our hospital was 53 months. (B) The MST did not differ between the elderly and non-elderly groups.
Figure 2
Figure 2
Survival probabilities according to the Kaplan–Meier method for patients treated with pirfenidone (A) and nintedanib (B), showing that the mean survival times (MSTs) did not differ between elderly and non-elderly groups in each treatment group.
Figure 3
Figure 3
Survival probabilities after treatment among patients with IPF and antifibrotic agent use for ≥1 year. The 2- and 5-year survival probabilities (89.0% and 52.4%, respectively) did not reach the median survival rate.
Figure 4
Figure 4
Cumulative incidence ratios of acute exacerbation of IPF. The ratios within 1, 2, and 3 years among patients with long-term antifibrotic agent use (≥1 year, n = 40) were 15.4%, 26.3%, and 36.0%, respectively (A). Patients with mild disease (JRS classifications I and II) showed a lower occurrence of AE compared to those with moderate to severe stages (classes III and IV) (B). Patients with GAP stage I showed a significantly lower incidence of AE compared to those with GAP stages II and III during the observational period (C). * means p value is less than 0.05.
Figure 5
Figure 5
Log-rank analysis showed a significantly higher cumulative incidence of AE in the pirfenidone group than that in the nintedanib group. ** means p value is less than 0.01.
Figure 6
Figure 6
Log-rank analysis showing comparable survival probabilities between longer (≥1 year) and shorter (<1 year) treatment durations (A). The cumulative incidence of AE is also comparable between two groups (B).
Figure 7
Figure 7
Treatment-based analysis in elderly patients with IPF. The cumulative incidence of acute exacerbation (AE) in patients administered nintedanib is significantly lower in those with prolonged treatment duration (≥1 year) compared to those with a shorter treatment duration (A). This trend was not observed for pirfenidone treatment (B). * means p value is less than 0.05.
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