Clinical significance of serum SP-D as a biomarker for antifibrotics in idiopathic pulmonary fibrosis (IPF): Post hoc analysis of a phase 3 trial of pirfenidone in Japan

Background: The heterogeneity in IPF poses a major challenge for management of IPF. Antifibrotic drugs suppress the disease progression, and they also improve the survival in some patients. However, no biomarker has been proved to predict the response to antifibrotics. Aims and Objectives: We evaluated the significance of serum markers as predictor for response to pirfenidone in patients in phase 3 trial in Japan. Methods: We analyzed the data from 267 patients with IPF in phase 3 trial of pirfenidone in Japan. Association of baseline serum SP-D levels was examined with changes from baseline in vital capacity (VC) and progression-free survival (PFS: the progression was defined as a ≥10% decline in VC from baseline and/or death). Results: When patients were divided into high and low SP-D groups by the median level at baseline (202 ng/mL), significantly better response (changes in VC at 52 weeks and PFS) to pirfenidone was observed in low SP-D group than in high SP-D group (Figure). Serum concentration of SP-D decreased during therapeutic course in pirfenidone groups, and the decline was significant from 8 weeks after the initiation of pirfenidone. Conclusions: Serum SP-D levels has the potential for a predictor of response to pirfenidone in patients with IPF, and for a biomarker to monitor the course of treatment.