Real-world effectiveness of a topical dihydroavenanthramide D formulation for chronic pruritus: A multicenter clinical study with molecular evidence of pruritogenic pathway modulation

Abstract

Chronic pruritus is a prevalent and clinically burdensome condition that substantially impairs quality of life and is sustained by complex interactions between neuro-immune signaling and epidermal barrier dysfunction. Central mediators implicated in this pruritogenic network include interleukin-4 (IL-4), interleukin-13 (IL-13), interleukin-31 (IL-31), substance P encoded by TAC1, and nerve growth factor (NGF). The aim of this study was to evaluate the real-world effectiveness of a topical formulation containing dihydroavenanthramide D (DHAvD), a neurokinin-1 receptor inhibitor, in combination with barrier-repairing agents for reducing pruritus severity in patients with chronic pruritus of diverse etiologies. A supportive molecular sub-study was also performed to determine whether clinical improvement was accompanied by modulation of cutaneous pruritogenic gene expression. A prospective, single-arm, multicenter clinical study was conducted in 1,000 patients with chronic pruritus of diverse etiologies. The formulation was applied twice daily for 14 days, and pruritus severity was assessed using the 12-Item Pruritus Severity Scale (12-PSS; range 3–22). In a molecular sub-study, 20 patients with chronic idiopathic pruritus underwent paired skin biopsies from symptomatic areas before and after treatment, and cutaneous mRNA expression of IL4, IL13, IL31, TAC1, and NGF was quantified by qRT-PCR. The mean 12-PSS score decreased from 11.37±3.71 at baseline to 5.64±2.87 at day 14 (d=−1.72; p<0.001), and 55.4% of participants achieved a ≥50% reduction in pruritus severity. The reduction in symptom severity was consistent across etiological subgroups (p=0.787). A clinically meaningful reduction was also observed among patients treated with the cream as monotherapy, with 12-PSS scores decreasing from 10.44±3.78 to 5.06±2.62 (d=−1.53; p<0.001). In the molecular sub-study, significant downregulation of all five target genes was observed, with effect sizes ranging from d=−0.62 for IL4 (p=0.013) to d=−2.64 for NGF (p<0.001). In conclusion, topical DHAvD combined with barrier-repairing agents was associated with clinically meaningful real-world reduction in chronic pruritus severity and supportive molecular evidence of multi-target pruritogenic pathway modulation. These findings warrant confirmation in randomized vehicle-controlled trials.