Gil Yosipovitch1, Sonja Ständer2, Matthew B Kerby3, James W Larrick4, Andrew J Perlman4, Edward F Schnipper4, Xiaoming Zhang3, Jean Y Tang5, Thomas Luger6, Martin Steinhoff7. 1. Miami Itch Center, Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, Florida. 2. Center for Chronic Pruritus, Department of Dermatology, University Hospital Münster, Münster, Germany. 3. Menlo Therapeutics Inc, Redwood City, California. 4. Velocity Pharmaceutical Development, LLC, South San Francisco, California. 5. Department of Clinical Dermatology, Stanford University, Redwood City, Stanford, California. 6. Department of Dermatology, University Hospital Münster, Münster. 7. Department of Dermatology, University of California San Diego, Dublin; Department of Dermatology, Weill Cornell University-Qatar, Hamad Medical Corporation, Doha, Qatar. Electronic address: MSteinhoff@hamad.qa.
Abstract
BACKGROUND: The substance P/neurokinin 1 receptor pathway is critical in chronic pruritus; anecdotal evidence suggests that antagonism of this pathway can reduce chronic itch. OBJECTIVE: To assess the safety and efficacy of the substance P/neurokinin 1 receptor antagonist serlopitant in treating chronic pruritus. METHODS:Eligible patients with severe chronic pruritus who were refractory to antihistamines or topical steroids were randomized to serlopitant, 0.25, 1, or 5 mg, or to placebo, administered once daily for 6 weeks as monotherapy or with midpotency steroids and emollients. The primary efficacy end point was percentage change in visual analog scale pruritus score from baseline. RESULTS: Serlopitant treatment resulted in a dose-dependent decrease in pruritus. The mean percentage decreases from baseline visual analog scale pruritus scores were statistically significantly larger with the 1- and 5-mg doses of serlopitant (P = .022 and P = .013, respectively) than with placebo at week 6. No significant safety or tolerability differences were detected among the groups. LIMITATIONS: The sample size was insufficient for subgroup analyses of the efficacy of serlopitant for chronic pruritus on the basis of underlying conditions. CONCLUSIONS: Serlopitant, 1 mg and 5 mg daily, was associated with a statistically significant reduction in chronic pruritus and was well tolerated (NCT01951274).
RCT Entities:
BACKGROUND: The substance P/neurokinin 1 receptor pathway is critical in chronic pruritus; anecdotal evidence suggests that antagonism of this pathway can reduce chronic itch. OBJECTIVE: To assess the safety and efficacy of the substance P/neurokinin 1 receptor antagonist serlopitant in treating chronic pruritus. METHODS: Eligible patients with severe chronic pruritus who were refractory to antihistamines or topical steroids were randomized to serlopitant, 0.25, 1, or 5 mg, or to placebo, administered once daily for 6 weeks as monotherapy or with midpotency steroids and emollients. The primary efficacy end point was percentage change in visual analog scale pruritus score from baseline. RESULTS: Serlopitant treatment resulted in a dose-dependent decrease in pruritus. The mean percentage decreases from baseline visual analog scale pruritus scores were statistically significantly larger with the 1- and 5-mg doses of serlopitant (P = .022 and P = .013, respectively) than with placebo at week 6. No significant safety or tolerability differences were detected among the groups. LIMITATIONS: The sample size was insufficient for subgroup analyses of the efficacy of serlopitant for chronic pruritus on the basis of underlying conditions. CONCLUSIONS: Serlopitant, 1 mg and 5 mg daily, was associated with a statistically significant reduction in chronic pruritus and was well tolerated (NCT01951274).
Authors: Caroline Perner; Cameron H Flayer; Xueping Zhu; Pamela A Aderhold; Zaynah N A Dewan; Tiphaine Voisin; Ryan B Camire; Ohn A Chow; Isaac M Chiu; Caroline L Sokol Journal: Immunity Date: 2020-10-23 Impact factor: 31.745