Change in serum surfactant protein (SP)-A, SP-D and KL-6 predict the therapeutic effect of antifibrotic drugs in IPF

Background: Serum surfactant protein (SP)-A, SP-D, and KL-6 are prognostic biomarkers of patients with idiopathic pulmonary fibrosis (IPF), however, the relationship with the therapeutic effect of antifibrotic drugs has not been investigated. Aim: To clarify whether serum SP-A, SP-D and KL-6 are therapeutic predictive markers of pirfenidone and nintedanib in patients with IPF. Methods: We retrospectively investigated patients with IPF who started pirfenidone or nintedanib between January 2014 and June 2018 at our hospital. The change in clinical parameters and serum SP-A, SP-D and KL-6 levels were evaluated. Patients with a > 10% decline in forced vital capacity (FVC) or a > 15% decline in diffusing capacity of the lung for carbon monoxide (DLco) from baseline to 6 months were classified as a deterioration group and the other was classified as an effective group. Results: Forty-nine patients were included (pirfenidone; 23, nintedanib; 26). Thirty-two patients were the effective group and 17 patients were the deterioration group. In the effective group, the change in serum SP-A, SP-D, and KL-6 from baseline to 3 and/or 6 months significantly decreased compared with the deterioration group. The change in serum SP-A and SP-D showed significant negative correlations with the change in %FVC and %DLCO. According to the logistic regression analysis, the decrease in SP-A from baseline to 3 months was a predictor of the effect at 6 months (odd’ ratio 0.88). Conclusions: Change in SP-A, SP-D and KL-6 represent the therapeutic effect of antifibrotic drugs. These may be therapeutic predictive biomarkers of antifibrotic drugs.