Blood Krebs von den Lungen-6 levels predict treatment response to antifibrotic therapy in patients with idiopathic pulmonary fibrosis

Abstract

Background Antifibrotic therapy can slow disease progression (DP) in patients with idiopathic pulmonary fibrosis (IPF). However, the prognostic biomarkers for DP in patients with IPF receiving antifibrotic therapy have not been identified. Therefore, we aimed to evaluate the prognostic efficacy of serum Krebs von den Lungen-6 (KL-6) for DP in patients with IPF receiving antifibrotic therapy. Methods The clinical data of 188 patients with IPF who initiated antifibrotic therapy at three tertiary hospitals was retrospectively analyzed. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, diffusing capacity for carbon monoxide ≥ 15%, acute exacerbation, or deaths during 6 months after antifibrotic therapy. Results The mean age of patients was 68.9 years, 77.7% were male, and DP occurred in 43 patients (22.9%) during follow-up (median, 7.6 months; interquartile range, 6.2–9.8 months). There was no difference in baseline KL-6 levels between the DP and no-DP groups; however, among patients with high baseline KL-6 levels (≥ 500 U/mL), changes in KL-6 levels over 1 month were higher in the DP group than those in the non-DP group, and higher relative changes in KL-6 over 1 month were independently associated with DP (odds ratio, 1.043; 95% confidence interval 1.005–1.084) in the multivariable logistic analysis adjusted for age and FVC. In the receiver operating characteristic curve analysis, the 1-month change in KL-6 was also useful for predicting DP (area under the curve = 0.707; P < 0.012). Conclusions Our data suggest that the relative change in KL-6 over 1 month might be useful for predicting DP in patients with IPF receiving antifibrotic therapy when baseline KL6 is high.

Radioproteomics stratifies molecular response to antifibrotic treatment in pulmonary fibrosis

“…However, differentiation between natural disease progression and treatment failure is difficult by means of conventional PFT and HRCT assessment 6 . Molecular response markers, including peripheral blood biomarkers may improve precision, but these are still in early developmental stages and may not fully reflect lung tissue phenotypes 7,38,39 . Over the last decade, radiomics has emerged as a powerful tool for drug response monitoring and predicting outcomes in various diseases, such as cancer, neurological disorders and recently also ILDs [40][41][42] .…”

“…Current evaluation of treatment response primarily relies on longitudinal lung function measurements, which are prone to intra-subject variability, can be influenced by extrapulmonary parameters, and lack insights into the underlying molecular response 5,6 . Liquid- or tissue-derived readouts could partially address these limitations, but validated biomarkers are not yet available and repeated lung biopsies are not a viable option due to the associated interventional risks 7 . Radiomics analysis of routinely performed high-resolution computed tomography (HRCT) scans has great potential to serve as a non-invasive solution for evaluation of treatment response in individual patients in four dimensions (3D space + time) 8,9 .…”

Enfermedad pulmonar intersticial difusa

“…Se ha demostrado que esta proteína está elevada, tanto en suero como en líquido broncoalveolar, en pacientes con enfermedad pulmonar intersticial difusa (EPID), tanto FPI como no FPI, comparada con sujetos sanos. Además, esta molécula podría ser de utilidad como marcador de progresión 12 , e incluso de respuesta al tratamiento 13 .…”

Acute Exacerbations of Interstitial Lung Diseases: Focus on Biomarkers

“…Another study identified increased KL-6 serum levels as a risk factor for AE-IPF in patients treated with nintedanib [ 16 ]. Baseline KL-6 levels, as well as serial changes of KL-6, were associated with progressive disease (including AE) in a cohort of 188 patients under antifibrotic treatment [ 17 ]. Despite these positive results, a meta-analysis of fourteen studies regarding the association of KL-6 levels with AE-IPF showed that the detection power of the biomarker is limited, and no relationship between biomarker concentrations and mortality was found.…”