Serum CCL18 Levels Predict Survival and Disease Progression in IPF Patients Treated with Antifibrotic Drugs

Introduction IPF is a progressive disease with a poor prognosis. Recently antifibrotic treatment with either pirfenidone or nintedanib were approved. Both drugs have been shown to slow disease progression. In previous studies undertaken before the approval of antifibrotic treatment we and others have reported on the predictive value of serum CCL18 concentration in patients not treated with antifibrotics.
Objective To investigate the predictive value of serum CCL18 concentrations on disease progression and mortality in a cohort of IPF patients treated with antifibrotic drugs. In addition, we genotyped the CCL18 promoter polymorphism to analyze a correlation between CCL18 concentration and the CCL18 genotype.
Methods IPF was defined according to the ATS/ERS criteria. The study was approved by the local ethics committee and all 119 patients signed informed consent prior to inclusion. Serum samples were harvested at initial diagnosis (baseline, prior to antifibrotic treatment) and during the antifibrotic treatment. Serum CCL18 concentrations were measured by ELISA. In addition, we genotyped the CCL18 promoter polymorphism (SNP rs2015086). Patients were followed for 24 months. Pulmonary function tests, including FVC% and DLCO% and survival status were analyzed.
Results At initial diagnosis the mean CCL18 concentration was 143 ng/ml. In comparison, the mean CCL18 concentration after 9 ± 4 months of antifibrotic treatment was 156 ng/ml (p = 0.00 187). The genotyping of the CCL18 promoter polymorphism showed that 69% of all patients were homozygous (AA-genotype), 30% had a heterozygous (AG-) genotype and only 1% was homozygous for allele 2 (GG-genotype). The mean CCL18 concentration in patients with an AA-genotype was 129 ± 46 ng/ml, for patients with AG-genotype considerably higher with 196 ± 80 ng/ml and for the GG-genotype even higher with 314 ng/ml (p = 0.0004). Serum CCL18 concentration keeps its predictive value in IPF patients treated with antifibrotics.
Conclusion Our data show a statistically significant slight increase in the serum CCL18 levels during an antifibrotic treatment irrespective of the antifibrotic drug. Furthermore, the CCL18 gene polymorphism has an impact on the CCL18 concentration which also works for prediction of survival and disease progression in IPF patients treated with antifibrotic drugs.