Systemic neurokinin-1 receptor antagonists mitigate chronic pruritus: A systematic review and meta-analysis

Abstract

Evidence suggests that substance P and neurokinin-1 receptor (NK1R) are often overexpressed in various chronic pruritus-inducing conditions. Several randomized controlled trials (RCTs) have demonstrated that targeting NK1R disrupts key itch signalling pathways, indicating the antipruritic effects of NK1R antagonists. However, these results remain to be validated. In this systematic review and meta-analysis, we synthesized and evaluated clinical evidence on the efficacy of systemic NK1R antagonists against chronic pruritus. PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched for relevant studies published from database inception to July 2024. We included RCTs and non-RCTs that compared NK1R antagonists with placebo and assessed reductions in patients' pruritus score. We further performed subgroup analyses by treatment duration, antagonist type and disease type. This study included 13 RCTs, 2 non-RCTs and 5 grey literatures (N = 2,876 patients). Pooled data indicated that systemic NK1R antagonists significantly reduced chronic pruritus (standardized mean difference [SMD]: -0.448; 95% confidence interval [CI]: -0.735 to -0.161; p = 0.002) with a significant association in achieving a clinically meaningful 4-point improvement. (OR: 1.631; 95% CI: 1.251 to 2.127; p = 0.000). Across the studies, 33.9% of patients in the systemic NK1R antagonists group achieved a clinically meaningful 4-point improvement, compared to 24.7% in the placebo group. The reductions in patients' pruritus scores were significantly greater with serlopitant (SMD: -0.292; 95% CI: -0.513 to -0.072; p = 0.009) and aprepitant (SMD: -1.55; 95% CI: -2.967 to -0.132; p = 0.032) than with placebo. Furthermore, significant reductions were observed across nonmalignant dermatological conditions (SMD: -0.390; 95% CI: -0.669 to -0.111; p = 0.006). Our study suggests that systemic NK1R antagonists, particularly serlopitant and aprepitant, hold a modest therapeutic effect for treating chronic pruritus, particularly in patients with nonmalignant dermatological conditions. Thus, clinicians can consider NK1R antagonists to effectively interrupt itch signalling in patients with chronic pruritus.

Keywords: NK‐1 antagonist; NK‐1 inhibitor; aprepitant; chronic itch; pruritus; serlopitant.