Monitoring Treatment Response in Eosinophilic Esophagitis
Monitoring Treatment Response in Eosinophilic Esophagitis
76 adult patients with active EoE were included in the primary study and had received treatment with either budesonide (n = 57) or placebo (n = 19). In 69 patients (budesonide: n = 51; placebo: n = 18) blood samples were sufficient for biomarker analyses. In the 7 remaining patients no or insufficient blood samples were available. The key characteristics of the 69 finally included subjects are listed in Table 1.
Almost all patients of the budesonide group (n = 51/52, 98%) showed histological remission, while in the placebo group, none of the 18 patients (n = 0/18, 0%) showed histological remission. The mean as well as the peak numbers of eos/mm hpf decreased significantly from baseline to end-of-treatment in the budesonide group, while no significant decrease was observed in the placebo group (Table 2). The total endoscopical intensity score decreased significantly from baseline to end-of treatment in the budesonide group, whereas there was no significant change in the placebo group. The dysphagia score improved significantly from baseline to end-of-treatment in both groups.
We observed a significant decrease in the mean AEC from baseline to end-of-treatment in budesonide recipients (380.2 ± 335.5 vs. 214.7 ± 179.3/mm, P = 0.0001), but not in placebo recipients (376.2 ± 230.6 vs. 393.7 ± 251.0/mm, P = 0.7231) (Figure 2a). Overall, there was a reduction in AEC in 35/48 (72.9%) of the budesonide recipients vs. 7/18 (38.9%) of the placebo recipients (P = 0.0199; Figure 3).
(Enlarge Image)
Figure 2.
Comparison of biomarker levels before (black bars, baseline) and after (grey bars, end-of-treatment (EOT)) treatment showed (a) significant decrease in absolute blood eosinophil count in budesonide but not in placebo recipients; (b) significant decrease in serum-eosinophilic-cationic-protein (ECP) in budesonide but not in placebo recipients; (c) significant decrease in serum-CCL-26 in budesonide but not in placebo recipients; (d) significant decrease in serum-CCL-17 in budesonide but not in placebo recipients; (e) no changes of serum-CCL-18 in budesonide and placebo recipients and (f) significant decrease in serum-mastcell-tryptase (MCT) in budesonide but not in placebo recipients.
(Enlarge Image)
Figure 3.
Under therapy, there was a reduction in absolute blood eosinophil count in 35/48 (72.9%) of the budesonide recipients vs. 7/18 (38.9%) of the placebo recipients (P = 0.0199).
Serum levels of CCL-17 (294.3 ± 158.7 vs. 257.9 ± 162.6 pg/mL, P = 0.0019), CCL-26 (26.7 ± 32.2 vs. 16.2 ± 16.3 pg/mL, P = 0.0058), ECP (45.5 ± 44.7 vs. 27.5 ± 25.0 μg/L, P = 0.0016) and MCT (5.3 ± 2.9 vs. 4.5 ± 2.6 μg/L, P = 0.0019) significantly decreased from baseline in budesonide, but not in placebo recipients (CCL-17: 293.8 ± 144.7 vs. 293.3 ± 157.2 pg/mL, P = 0.9869; CCL-26: 18.2 ± 13.2 vs. 15 ± 14.3 pg/mL, P = 0.0502; ECP: 37.8 ± 27.6 vs. 44.1 ± 54.3 μg/L, P = 0.5840; MCT: 5.4 ± 5.3 vs. 5.3 ± 5.6 μg/L, P = 0.6323). A significant change in serum-CCL-18 was neither observed in budesonide recipients (53.4 ± 23.6 vs. 49.7 ± 18.7 ng/mL, P = 0.0902) nor in placebo recipients (46.3 ± 12.5 vs. 44.4 ± 14.3 ng/mL, P = 0.5864) (Figure 2b–f).
We compared the biomarker levels of atopic (n = 39) with non-atopic (n = 30) EoE patients at baseline. No significant differences were observed for any biomarker (Table 3).
We observed a significant correlation of AEC with oesophageal eosinophil density at baseline (r = 0.28, P = 0.0236) and at end-of-treatment (r = 0.42, P = 0.004). We did not find a significant correlation of AEC with total dysphagia score or total endoscopy score. Serum ECP significantly correlated with total endoscopy score at baseline (r = 0.27, P = 0.0249), but not at end-of-treatment. There was no significant correlation of serum ECP with the dysphagia score and with the oesophageal eosinophil density at baseline and at end-of-treatment. Serum-CCL-17, -CCL-26 and -MCT did not show any significant correlations with histology, dysphagia score or endoscopy score.
In ROC-AUC analyses post-treatment values of AEC were significantly associated with the primary end point of histological remission (ROC-AUC 0.754; 95% CI: 0.617–0.891; P = 0.0003). Youden-index-calculation provided a sensitivity of 88% and specificity of 56% for a cut-off of 300 eosinophils/mm. No significant association for the other parameters was observed.
Results
Patient Characteristics
76 adult patients with active EoE were included in the primary study and had received treatment with either budesonide (n = 57) or placebo (n = 19). In 69 patients (budesonide: n = 51; placebo: n = 18) blood samples were sufficient for biomarker analyses. In the 7 remaining patients no or insufficient blood samples were available. The key characteristics of the 69 finally included subjects are listed in Table 1.
Histological, Endoscopic and Clinical Response
Almost all patients of the budesonide group (n = 51/52, 98%) showed histological remission, while in the placebo group, none of the 18 patients (n = 0/18, 0%) showed histological remission. The mean as well as the peak numbers of eos/mm hpf decreased significantly from baseline to end-of-treatment in the budesonide group, while no significant decrease was observed in the placebo group (Table 2). The total endoscopical intensity score decreased significantly from baseline to end-of treatment in the budesonide group, whereas there was no significant change in the placebo group. The dysphagia score improved significantly from baseline to end-of-treatment in both groups.
Biomarkers
We observed a significant decrease in the mean AEC from baseline to end-of-treatment in budesonide recipients (380.2 ± 335.5 vs. 214.7 ± 179.3/mm, P = 0.0001), but not in placebo recipients (376.2 ± 230.6 vs. 393.7 ± 251.0/mm, P = 0.7231) (Figure 2a). Overall, there was a reduction in AEC in 35/48 (72.9%) of the budesonide recipients vs. 7/18 (38.9%) of the placebo recipients (P = 0.0199; Figure 3).
(Enlarge Image)
Figure 2.
Comparison of biomarker levels before (black bars, baseline) and after (grey bars, end-of-treatment (EOT)) treatment showed (a) significant decrease in absolute blood eosinophil count in budesonide but not in placebo recipients; (b) significant decrease in serum-eosinophilic-cationic-protein (ECP) in budesonide but not in placebo recipients; (c) significant decrease in serum-CCL-26 in budesonide but not in placebo recipients; (d) significant decrease in serum-CCL-17 in budesonide but not in placebo recipients; (e) no changes of serum-CCL-18 in budesonide and placebo recipients and (f) significant decrease in serum-mastcell-tryptase (MCT) in budesonide but not in placebo recipients.
(Enlarge Image)
Figure 3.
Under therapy, there was a reduction in absolute blood eosinophil count in 35/48 (72.9%) of the budesonide recipients vs. 7/18 (38.9%) of the placebo recipients (P = 0.0199).
Serum levels of CCL-17 (294.3 ± 158.7 vs. 257.9 ± 162.6 pg/mL, P = 0.0019), CCL-26 (26.7 ± 32.2 vs. 16.2 ± 16.3 pg/mL, P = 0.0058), ECP (45.5 ± 44.7 vs. 27.5 ± 25.0 μg/L, P = 0.0016) and MCT (5.3 ± 2.9 vs. 4.5 ± 2.6 μg/L, P = 0.0019) significantly decreased from baseline in budesonide, but not in placebo recipients (CCL-17: 293.8 ± 144.7 vs. 293.3 ± 157.2 pg/mL, P = 0.9869; CCL-26: 18.2 ± 13.2 vs. 15 ± 14.3 pg/mL, P = 0.0502; ECP: 37.8 ± 27.6 vs. 44.1 ± 54.3 μg/L, P = 0.5840; MCT: 5.4 ± 5.3 vs. 5.3 ± 5.6 μg/L, P = 0.6323). A significant change in serum-CCL-18 was neither observed in budesonide recipients (53.4 ± 23.6 vs. 49.7 ± 18.7 ng/mL, P = 0.0902) nor in placebo recipients (46.3 ± 12.5 vs. 44.4 ± 14.3 ng/mL, P = 0.5864) (Figure 2b–f).
Comparison of Atopic With Non-atopic Patients
We compared the biomarker levels of atopic (n = 39) with non-atopic (n = 30) EoE patients at baseline. No significant differences were observed for any biomarker (Table 3).
Correlation of Biomarker Levels With Histology, Dysphagia and Endoscopy Score
We observed a significant correlation of AEC with oesophageal eosinophil density at baseline (r = 0.28, P = 0.0236) and at end-of-treatment (r = 0.42, P = 0.004). We did not find a significant correlation of AEC with total dysphagia score or total endoscopy score. Serum ECP significantly correlated with total endoscopy score at baseline (r = 0.27, P = 0.0249), but not at end-of-treatment. There was no significant correlation of serum ECP with the dysphagia score and with the oesophageal eosinophil density at baseline and at end-of-treatment. Serum-CCL-17, -CCL-26 and -MCT did not show any significant correlations with histology, dysphagia score or endoscopy score.
Prediction of Histological Remission
In ROC-AUC analyses post-treatment values of AEC were significantly associated with the primary end point of histological remission (ROC-AUC 0.754; 95% CI: 0.617–0.891; P = 0.0003). Youden-index-calculation provided a sensitivity of 88% and specificity of 56% for a cut-off of 300 eosinophils/mm. No significant association for the other parameters was observed.
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