PracticeUpdate Dermatology Best of 2018

EDITOR’S PICKS 12

Serlopitant for the Treatment of Chronic Pruritus Journal of the American Academy of Dermatology Take-home message

" This study also demonstrates that more research is needed in evaluating the basic pathophysiology of pruritus. " COMMENT By Erin E. Boh MD, PhD C hronic pruritus poses a signifi- cant burden on society in terms of healthcare cost and treatment challenges. Additionally, many systemic diseases are also known to be associated with pruritus. Currently, the pathophysiology of pruritus is unclear, but we do know that the substance P/neurokinin 1 recep- tor (NK1R) pathway is critical in chronic pruritus. In this original article, the authors eval- uated the safety and efficacy of novel agent serlopitant, an NK1R antago- nist, for treatment of chronic pruritus in patients with disparate dermatologic diseases and idiopathic pruritus. In this study, serlopitant treatment resulted in a dose-dependent decrease in pruritus in all groups as well as improvement in the DLQI (quality-of-life assay). Nearly 45% of patients had a pri- mary dermatologic disease. However, it should be noted that improvement in pruritus occurred in the treatment group regardless of the underlying der- matologic disease. This is particularly exciting as treatments for chronic pruri- tus are not particularly helpful. This was a small patient population, and the high placebo rates should not detract from the potential significance of this study. This study also demonstrates that more research is needed in evaluating the basic pathophysiology of pruritus. If we are able to discover the key players and pathways in pruritus, we will be able to construct drugs that can target these pathways to block its effects. Dr. Boh is Chairman & Professor of Dermatology at Tulane University Health Sciences Center in New Orleans, Louisiana.

• The authors assessed the safety and efficacy of serlopitant in patients with chronic pruritus associated with dermatologic and non-dermatologic conditions. Patients were randomized to receive either placebo (n=64), or serlopitant 0.25 mg (n=64), 1 mg (n=65), and 5 mg (n=64). No adverse events were detected. After 6 weeks, patients receiving 1 mg or 5 mg of serlopitant had a marked decrease in pruritus scores compared with patients receiving placebo. Differences emerged at 3 weeks after treatment initiation and remained at final follow-up visit 4 weeks after completing treatment. • The results suggest that serlopitant is well-tolerated and reduces pruritus in patients with severe chronic pruritus from several dermatologic and non-dermatologic conditions that were refractory to antihistamines and corticosteroids. Jeffrey F. Scott MD

Abstract BACKGROUND The substance P/neurokinin 1 receptor (NK1R) pathway is critical in chronic pruritus; anecdotal evidence suggests antag- onism of this pathway can reduce chronic itch. OBJECTIVE To assess the safety and efficacy of the NK1R 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 placebo, administered once daily for 6 weeks as monotherapy or with mid- potency steroids and emollients. The primary efficacy end point was percentage change in Visual Analog Scale (VAS) pruritus score from baseline. RESULTS Serlopitant treatment resulted in a dose-dependent decrease in pruritus. Mean percentage decreases from baseline VAS

pruritus scores were statistically significantly larger for the 1- and 5-mg doses of serlopitant (P = .022 and P = .013) versus 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 serlopi- tant for chronic pruritus based on underlying conditions. CONCLUSIONS Serlopitant 1 mg and 5 mg daily was associated with a statistically significant reduction in chronic pruritus and was well tolerated. Serlopitant for the Treatment of Chronic Pruritus: Results of a Randomized, Multicenter, Placebo- Controlled Phase 2 Clinical Trial. J Am Acad Dermatol 2018 Feb 17;[EPub Ahead of Print], G Yosipovitch, S Ständer, MB Kerby, et al. www.practiceupdate.com/c/64715

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