Effects of low-dose pirfenidone on survival and lung function decline in patients with idiopathic pulmonary fibrosis (IPF): Results from a real-world study

Abstract

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown etiology. In several randomized clinical trials, and in the clinical practice, pirfenidone is used to effectively and safely treat IPF. However, sometimes it is difficult to use the dose of pirfenidone used in clinical trials. This study evaluated the effects of low-dose pirfenidone on IPF disease progression and patient survival in the real-world. Methods This retrospective, observational study enrolled IPF patients seen at the time of diagnosis at a single center from 2008 to 2018. Longitudinal clinical and laboratory data were prospectively collected. We compared the clinical characteristics, survival, and pulmonary function decline between patients treated and untreated with various dose of pirfenidone. Results Of 295 IPF patients, 100 (33.9%) received pirfenidone and 195 (66.1%) received no antifibrotic agent. Of the 100 patients who received pirfenidone, 24 (24%), 50 (50%), and 26 (26%), respectively, were given 600, 1200, and 1800 mg pirfenidone daily. The mean survival time was 57.03 ± 3.90 months in the no-antifibrotic drug group and 73.26 ± 7.87 months in the pirfenidone-treated group (p = 0.027). In the unadjusted analysis, the survival of the patients given pirfenidone was significantly better (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.48–0.99, p = 0.04). After adjusting for age, gender, body mass index, and the GAP score [based on gender (G), age (A), and two physiological lung parameters (P)], survival remained better in the patients given pirfenidone (HR = 0.56, 95% CI: 0.37–0.85, p = 0.006). In terms of pulmonary function, the decreases in forced vital capacity (%), forced expiratory volume in 1 s (%) and the diffusing capacity of lung for carbon monoxide (%) were significantly smaller (p = 0.000, p = 0.001, and p = 0.007, respectively) in patients given pirfenidone. Conclusions Low-dose pirfenidone provided beneficial effects on survival and pulmonary function decline in the real-world practice.

The influence of immortal time bias in observational studies examining associations of antifibrotic therapy with survival in idiopathic pulmonary fibrosis: A simulation study

“…Of the 16 studies reviewed, we found that 14 studies were detected with presence of ITB based on the ITB checklist, while there were insufficient data for assessment of two others. This is consistent with a recently published Letter to Editor (26) that summarized observational studies reporting the effectiveness of antifibrotic therapy on mortality of IPF and identified 14 studies (16-19, 35,41,42,44,45,[53][54][55][56][57] presenting ITB. Compared to a previous study (26), we have included more studies and have provided more detailed information by using the ITB checklist and conducting a simulation study to identify and account for ITB in IPF studies.…”

Factors associated with dose reduction of pirfenidone in patients with idiopathic pulmonary fibrosis: A study based on real-world clinical data

“…Another phase III trial in Japan reported a significant difference in vital capacity (approximately 0.07 L) between the high-dose (1800 mg/day) and placebo groups (p = 0.0416) and a significant difference in vital capacity (approximately 0.09 L) between the low-dose (1200 mg/day) and placebo groups (p = 0.0394), suggesting that low-dose pirfenidone is effective [12]. A study assessing real-world pirfenidone data in South Korea reported that relatively a low dose of pirfenidone (�1200 mg/day) can have an effect on pulmonary function decline [14,15]. In our study, we compared changes in FVC and DLCO between the standard and low-dose groups and found no significant difference in efficacy with dose, which is comparable to the findings of previous studies.…”

“…Although some studies have reported that low-dose pirfenidone is not inferior to a standard dose [12,14,15], there are few reports focused on the side effects associated with pirfenidone and reduced doses. Thus, we aimed to investigate clinical characteristics of and factors associated with dose reduction of pirfenidone in a real-world setting.…”

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

“…Recently, a systematic review and meta-analysis of RCTs also indicated that Pirfenidone treatment was associated with a longer progression-free-survival and a lower incidence of acute exacerbation (Wu et al, 2021). In the real-world practice, Pirfenidone also provided beneficial effects on survival and pulmonary function decline (Lee et al, 2021). Moreover, A post hoc analysis of ASCEND and CAPACITY program suggested a clinically relevant benefit of Pirfenidone in IPF patients with more advanced lung function impairment (Nathan et al, 2019).…”