POS0859 C-REACTIVE PROTEIN AND INTERLEUKIN-6: POTENTIAL BIOMARKERS OF DISEASE ACTIVITY AND TREATMENT RESPONSE IN SYSTEMIC SCLEROSIS-INTERSTITIAL LUNG DISEASE

Abstract

BackgroundClinically feasible and valid biomarkers of systemic sclerosis-interstitial lung disease (SSc-ILD) are needed. While promising candidate biomarkers are under investigation (e.g., KL-6, CCL-8), clinical assays for these proteins are not currently available. C-reactive protein (CRP) measurements are feasible, cost-effective, and have been shown to predict mortality in SSc.1 Measuring interleukin (IL)-6, a proinflammatory cytokine implicated in SSc-ILD pathogenesis, is also feasible in most clinical settings.Objectives(1) To investigate whether CRP and IL-6 levels change in response to treatment with immunosuppression in SSc-ILD; (2) To explore whether the change in CRP and IL-6 predict the future course of forced vital capacity (FVC).MethodsCRP and IL-6 levels were measured in serum at baseline and after 12 months in participants of Scleroderma Lung Study (SLS) II (patients with active SSc-ILD receiving 24 months of mycophenolate or 12 months cyclophosphamide followed by 12 months of placebo2). Measured values were log-transformed to remove skewness. The FVC%-predicted was measured every 3 months over the course of 24 months. Spearman’s correlations evaluated the relationship between baseline CRP or IL-6 measurements and other patient parameters. Paired t-tests were used to compare the change in individual CRP and IL-6 measurements from baseline to 12 months. Linear mixed effects models were used to examine the relationship between the change in CRP and IL-6 (baseline to 12 months) and the subsequent course of the FVC (12 to 24 months). All analysis were performed for the entire cohort and separately by treatment arm.ResultsOf the 142 participants of SLS II, 101 had CRP and IL-6 measurements at baseline and 12 months. Baseline CRP and IL-6 levels correlated significantly with higher modified Rodnan skin score (CRP: r=0.3, P=0.005; IL-6: r=0.2, P=0.01) and shorter disease duration (CRP: r=-0.3, P=0.005; IL-6: r=-0.2, P=0.01) and were higher in patients with diffuse SSc (CRP: P=0.007; IL-6: P=0.01). Relationships to baseline FVC and DLCO were not observed. CRP decreased significantly from baseline to 12 months in the whole group (P=0.01), but the decrease was slightly greater in patients randomized to mycophenolate versus cyclophosphamide (-0.47 vs. -0.33 ug/mL). IL-6 also decreased from baseline to 12 months in the whole group with a trend towards significance (P=0.10) (Figure 1). The mean decrease in IL-6 was again slightly greater in patients randomized to mycophenolate versus cyclophosphamide (-0.31 vs. -0.10 pg/mL). After controlling for baseline FVC and treatment arm in the mixed effects model, there was a relationship between the decrease in CRP from baseline to 12 months and an improved course of FVC 12 to 24 months (Estimate -0.64), but this did not reach significance (P=0.14). However, after controlling for baseline FVC and treatment arm, a greater decrease in IL-6 from baseline to 12 months was significantly associated with a greater improvement in FVC from 12 to 24 months (Estimate -1.28; P=0.01).Figure 1.Change in CRP (A) and IL-6 (B) from baseline to 12 months by treatment arm in SLS II. CYC=cyclophosphamide (Blue), MMF=mycophenolate (red)ConclusionPatients with active SSc-ILD receiving one year of immunosuppressive therapy in the SLS II study experienced reductions in their CRP and IL-6 levels over this interval. The magnitude of the decrease in CRP and IL-6 over the first year also correlated with the course of FVC over the ensuing 12 months. These findings suggest a dynamic relationship between CRP and IL-6 measurements and the course of SSc-ILD in patients on immunosuppressive therapy. Further investigation of these findings is warranted.