Phase 2 trial of a neurokinin-1 receptor antagonist for the treatment of chronic itch in patients with epidermolysis bullosa: A randomized clinical trial

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

卷:82

Article

Chiou, Albert S.¹  Choi, Sara¹  Barriga, Melissa¹  Dutt-Singkh, Yana¹  Solis, Daniel C.²  Nazaroff, Jaron³  Bailey-Healy, Irene¹  Li, Shufeng¹  Shu, Kim⁴  Joing, Mark⁴  Kwon, Paul⁴  Tang, Jean Y.¹ 

[1] Stanford Univ, Sch Med, Dept Dermatol, 450 Broadway St,Pavil C,2nd Floor, Redwood City, CA 94063 USA

[2] Univ Calif Riverside, Dept Internal Med, Riverside, CA 92521 USA

[3] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA

[4] Menlo Therapeut Inc, Redwood City, CA USA

关键词: chronic itch;    drug response;    epidermolysis bullosa;    neurokinin 1 receptor;    NK1 receptor;    NK1 receptor antagonist;    pruritus;    serlopitant;    substance P;   

DOI  :  10.1016/j.jaad.2019.09.014

来源: Elsevier

【 摘 要 】

Background: Chronic pruritus causes major morbidity in epidermolysis bullosa (EB). The substance P-neurokinin 1 receptor (SP-NK1) pathway is a promising target for treating EB-related pruritus. Objective: To evaluate the safety and efficacy of the oral NK1 receptor antagonist serlopitant in treating moderate-severe pruritus in EB. Methods: The study randomized 14 patients to serlopitant or placebo for 8 weeks, followed by a 4-week washout and optional open-label extension. The primary end point was change in itch as measured by the Numeric Rating Scale. Secondary end points were change in itch during dressing changes and wound size. Results: We observed greater itch reduction with serlopitant, equivalent to a 0.64-point comparative reduction on the 11-point Numeric Rating Scale by week 8, although this failed to meet statistical significance (P = .11). More serlopitant patients achieved $3-point reduction compared with placebo (43% vs 14%, P = .35). In post hoc analysis excluding 1 patient with a concurrent seborrheic dermatitis flare, serlopitant achieved significantly greater median itch reduction from baseline by week 4 (similar to 2 points vs 0, P = .01). We observed no statistically significant differences in secondary end points. Serlopitant was well-tolerated. Limitations: Small sample size due to disease rarity. Conclusion: The potential itch reduction with serlopitant observed in this trial will be pursued by a larger powered trial (NCT03836001).

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