Fecal Lactoferrin (fLac) and Calprotectin (fCal) as Surrogate Markers of Mucosal Healing: Post-hoc Analysis from the PURSUIT SC Induction Study

Abstract

Introduction: Previously we reported greater improvement in both fLac&fCal levels in UC pts who showed clinical response&endoscopic healing in PURSUIT SC induction golimumab(GLM)study1. These post-hoc analyses assessed association of fecal inflammatory markers, fLac&fCal, with Mayo endoscopy subscores using data from this study. Methods: The Ph3 portion of PURSUIT-SC was a multicenter, rand, PBO-controlled dble-blind study to evaluate safety&efficacy of induction therapy with SC GLM. Pts with Mayo scores of 6-12 inclusive, including endoscopic subscore >2 were rand to PBO/PBO, GLM 200mg/100mg, or GLM 400mg/ 200mg at Wks 0&2. Mucosal healing was assessed at Wk6 using Mayo endoscopy subscore. Stool samples were collected for fLac& fCal Wk0 thru Wk6. Assays for fLac&fCal concentrations were performed using validated methods. The area under a ROC curve(AUC)assessed the association of baseline&Wk6 fLac&fCal with Mayo endoscopy subscores of 0(defining normal or inactive disease)& subscores of 0 or 1(defining endoscopic healing in this study)at Wk6. Various cut offs of fLac&fCal concentrations were explored to determine balance of sensitivity&specificity for endoscopy subscores of 0 or 0 or 1. Results: Mayo endoscopy subscores of 0 or 1 were associated with lowest concentrations of fLac&fCal(Table). Baseline fLac&fCal were poor predictors for endoscopic healing at Wk6(AUCs< 0.63). Area under ROC curve analysis showed fLac&fCal at Wk6 are fair surrogate markers for normal/inactive endoscopic disease activity(endoscopy subscore of 0)at Wk6 with AUCs of 0.77&0.79, resp. Similar AUCs were observed for endoscopy subscores of 0 or 1. Cutoffs of fLac < 50 μg/ml & fCal < 250mg/kg at Wk6 offered reasonable sensitivity&specificity(fLac 0.74, 0.67 & fCal 0.79, 0.70)for normal/inactive endoscopic disease activity at Wk6. In contrast, cutoffs of fLac < 100μg/ml & fCal < 500mg/kg at Wk6 offered similarly reasonable sensitivity&specificity(fLac 0.73, 0.63 & fCal 0.74, 0.64)for endoscopy subscores of 0 or 1. Conclusion: At Wk6, Mayo endoscopy subscores were positively associated with levels of fLac&fCal. Cut-offs of fLac < 50μg/ml & fCal < 250mg/kg at Wk6 showed reasonable sensitivity&specificity for normal/endoscopic disease activity. Overall these data suggest that fecal inflammatory marker levels might be useful surrogates for endoscopic improvement.Table 1: Fecal Inflammatory Marker Concentrations and Mayo Endoscopy Subscores at Week 6