Baseline and longitudinal changes in blood biomarkers for predicting clinical outcomes in pirfenidone-treated idiopathic pulmonary fibrosis: a prospective observational study

This study investigated blood biomarkers for predicting lung function decline or disease progression in patients with idiopathic pulmonary fibrosis (IPF) receiving pirfenidone. Data from a multicenter prospective observational study in South Korea were analyzed. Patients with available blood samples at baseline and 6 months were followed up for 12 months. We assessed the predictive value of baseline levels and 6-month changes in nine biomarkers for forced vital capacity (FVC) deterioration and disease progression. FVC deterioration was defined as an absolute decline of ≥ 10% points in FVC % predicted at 12 months, while disease progression included FVC deterioration, hospitalization, or death. A total of 118 patients were included, with a mean age of 68.9 years and 82.2% being men. Median follow-up and treatment duration were 350 days. Greater FVC decline was observed in patients with higher baseline biomarker levels. Elevated baseline CCL18 predicted FVC deterioration in unadjusted analysis, and higher baseline CCL18 and KL-6 were independently associated with disease progression after adjusting for age, sex, and baseline FVC. Baseline CA-125 was associated with FVC deterioration after adjustment, and its relative changes over 6 months were associated with FVC deterioration and showed a trend toward disease progression. When comparing predictive models, individual biomarkers showed discriminative performance comparable to clinical variables, and their addition to clinical variables resulted in a slight, non-significant improvement in performance (area under the curve for FVC deterioration increasing from 0.769 to 0.824). These findings suggest that several blood biomarkers, particularly CCL18, KL-6, and CA-125, may provide additional prognostic information for IPF patients receiving pirfenidone and warrant further investigation.