Neighbors M, et al. - Researchers assessed the prognostic and predictive properties of biomarkers across multiple endpoints for patients with idiopathic pulmonary fibrosis (IPF) treated with pirfenidone and ascertained whether or not they are modulated by pirfenidone treatment. The most consistent predictor of disease progression across IPF cohorts was blood CCL18 concentrations. These concentrations had a potential to inform new target discovery and clinical trial design.

Methods

• Experts performed post-hoc analyses of test and replication cohorts from CAPACITY 004, CAPACITY 006, and ASCEND trials for the plasma proteins CCL13, CCL17, CCL18, CXCL13, CXCL14, COMP, interleukin 13, MMP3, MMP7, osteopontin, periostin, and YKL40.
• The participants eligible for this study had IPF and received pirfenidone 2403 mg/day or placebo in CAPACITY (test cohort) or ASCEND (replication cohort), were aged 40–80 years, and without missing biomarker data at baseline.
• The primary analysis for identifying the biomarkers that were consistently prognostic for clinical outcome measures was the correlation between biomarker concentrations at baseline and absolute change in percentage of predicted forced vital capacity (FVC_%pred) at 12 months (CAPACITY week 48, ASCEND week 52) in the placebo group.
• In the replication cohort, they further assessed the biomarkers within the test cohort that met predefined success criteria of a prognostic p value less than 0·10 from multivariate analysis.
• Moreover, they calculated the predictive impact size (ie, biomarkers that were predictive for benefit from pirfenidone) as the difference in FVC_%predtreatment effect (pirfenidone in relation to placebo) between high vs low biomarker subgroups at week 48 (test cohort) or week 52 (replication cohort).

Results

• Findings suggested that several baseline biomarkers (CCL13, CCL18, COMP, CXCL13, CXCL14, periostin, and YKL40) were prognostic for progression outcomes in the placebo groups of the test cohort.
• Nonetheless, for absolute change in percentage of FVC_%pred in both the test (p=0·032) and replication (p=0·004) cohorts, only CCL18 was consistently prognostic.
• Regardless of baseline biomarker concentration, pirfenidone treatment benefit was consistent.