057 The role of substance P and its receptor NK1R in chronic prurigo: Results from a randomized, controlled trial with topical aprepitant

Substance P (SP) and the neurokinin 1 receptor (NK1R) are held to be involved in the pathogenesis of chronic prurigo (CPG). Here, we assessed SP serum levels, cutaneous NK1R expression, and the effects of topical aprepitant, an NK1R antagonist, in CPG patients. As compared to controls, SP was increased in the serum of CPG patients (163.5 pg/ml ±17.3 vs. 43.7 pg/ml ±20.1; P<0.001), and expression of NK1R and number of NK1R positive cells was higher in lesional vs. non-lesional skin of CPG patients (intensity of IR: 1.7 ±0.2 vs. 1 ±0.3; p<0.05 and number of NK1R-positive cells/mf: 53.2 ±10.3 vs. 21.7 ±9.0; p<0.05). In a randomized, placebo-controlled, split-sided, double-blind trial, topical aprepitant reduced pruritus intensity as assessed by VAS by >50% from baseline to day 28 (-35.2), but so did placebo vehicle (-38.1, P=0.76). Overall CPG scores improved significantly by day 28 in both treatment groups, with no significant difference between the two (P=0.32). Our findings imply both SP and NK1R are involved in the pathogenesis of CPG. Parallel group-designed trials are needed to assess the efficacy of topical aprepitant treatment in CPG.