serlopitant and Pruritus

Topics: Animals; Antipruritics; Chronic Disease; Humans; Isoindoles; Neurokinin-1 Receptor Antagonists; Pruritus; Quality of Life; Receptors, Neurokinin-1

Pruritus, a common symptom of psoriasis, negatively affects quality of life; however, treatment of lesional skin does not consistently alleviate psoriatic itch.. To examine the effects of serlopitant, an oral, once-daily neurokinin 1 receptor antagonist, for treatment of psoriatic pruritus in a phase 2, randomized clinical trial (NCT03343639).. Patients (n = 204) were randomized to receive serlopitant, 5 mg, or placebo daily for 8 weeks. Eligible adult patients had plaque psoriasis for ≥6 months, plaques covering ≤10% of body surface area, pruritus for ≥4 weeks, and Worst Itch Numeric Rating Scale (WI-NRS) score ≥7 at the initial screening.. Participants (54.2% women) had a mean age of 47.5 years and 85.2% were white. Mean baseline WI-NRS scores were 8.3 for serlopitant and 8.1 for placebo. The WI-NRS 4-point response rate at 8 weeks (primary end point) was 33.3% for serlopitant vs 21.1% for placebo (P = .028); at 4 weeks the rates were 20.8% for serlopitant vs 11.5% for placebo (P = .039). Treatment-related adverse events were reported for 4.9% of serlopitant-treated and 4.0% of placebo-treated patients.. This was a phase 2 study with a small study population. Patients with severe psoriasis were excluded.. Serlopitant significantly reduced pruritus associated with mild to moderate psoriasis, supporting continued development of serlopitant for this patient population.

Topics: Adult; Diarrhea; Female; Headache; Humans; Isoindoles; Male; Middle Aged; Nasopharyngitis; Neurokinin-1 Receptor Antagonists; Pruritus; Psoriasis; Severity of Illness Index

There is an unmet need for psychometrically sound instruments to measure pruritus associated with prurigo nodularis (PN).. To evaluate the psychometric properties of the itch numeric rating scale (itch NRS), both the Worst Itch Numeric Rating Scale (WI-NRS) and the Average Itch Numeric Rating Scale (AI-NRS).. This secondary analysis is based on a secondary end point of a phase 2 randomized clinical trial of serlopitant for treatment of pruritus associated with PN. This randomized, double-blind, placebo-controlled study was conducted at 15 sites in Germany. Eligible patients were aged 18 to 80 years and had generalized PN for more than 6 weeks that was refractory to previous antipruritic therapies. Patients were required to have a visual analog scale itch score of 7 or higher at screening. Data were collected from July 2014 to June 2016 and analyzed from June 2016 to January 2017.. The itch NRS (AI-NRS and WI-NRS) was correlated together with the following measures: the electronic verbal rating scale (eVRS) for itch self-categorization, average itch visual analog scale (AI-VAS), worst itch visual analog scale (WI-VAS), the pruritus-specific quality-of-life rating instrument ItchyQoL, Dermatology Life Quality Index (DLQI), and Prurigo Activity and Severity Score (items 7b and 7a: percentage healed prurigo lesions and percentage of prurigo lesions with excoriations).. There were 123 participants in this study; the mean (SD) age of participants was 57.3 (11.58) years, and 58 (47.2%) were male. Strong associations (r ≥ 0.5) were observed between itch NRS items (WI-NRS and AI-NRS) and AI-VAS (24 hours) at weeks 2, 4, and 8 (r = 0.72-0.90; P < .001). Similar strong associations were also observed between itch NRS items and WI-VAS (24 hours) and eVRS for itch severity across weeks 2, 4, and 8 (r = 0.65-0.92; all P < .001). Strong correlations were seen between change scores for WI-NRS and WI-VAS and AI-VAS (r = 0.76 and 0.70, respectively; both P < .001). Similar findings were seen for AI-NRS, where correlations between change scores for WI-VAS and AI-VAS were 0.71 and 0.72, respectively (both P < .001). Analyses for the itch NRS items also showed that test-retest reliability was acceptable and provided evidence of acceptable convergent validity based on the eVRS and visit verbal rating score for itch self-categorization, ItchyQoL, and DLQI.. Results from this secondary analysis show that the itch NRS items WI-NRS and AI-NRS have good psychometric properties for pruritus associated with PN and should be considered acceptable tools for assessing pruritus in future clinical trials of PN.. ClinicalTrials.gov Identifier: NCT02196324.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Double-Blind Method; Female; Germany; Humans; Isoindoles; Male; Middle Aged; Prurigo; Pruritus; Psychometrics; Quality of Life; Reproducibility of Results; Severity of Illness Index; Visual Analog Scale; Young Adult

Anecdotal evidence suggests that neurokinin 1 receptor antagonism reduces pruritus intensity in chronic pruritic conditions such as prurigo nodularis (PN).. This study assessed safety and efficacy of the neurokinin 1 receptor antagonist serlopitant for treatment of pruritus in PN.. In this randomized, double-blind, placebo-controlled study, 128 patients with chronic, treatment-refractory PN for more than 6 weeks received serlopitant, 5 mg, or placebo orally once daily for 8 weeks. The primary end point was change in average itch visual analog scale score at weeks 4 and 8.. Average itch visual analog scale scores significantly improved with serlopitant versus with placebo at weeks 4 and 8: the least squares mean difference (serlopitant minus placebo) was -1.0 at week 4 (P = .02) and -1.7 at week 8 (P < .001). The least squares mean difference between serlopitant and placebo reached statistical significance at week 2 (-0.9 [P = .011]). The most frequently reported treatment-emergent adverse events in the serlopitant group were nasopharyngitis, diarrhea, and fatigue.. The 8-week duration may be insufficient to assess clinically relevant resolution of PN lesions.. Serlopitant reduced pruritus in patients with treatment-refractory PN and was well tolerated.

Topics: Adult; Aged; Chronic Disease; Diarrhea; Double-Blind Method; Fatigue; Female; Humans; Isoindoles; Male; Middle Aged; Nasopharyngitis; Neurokinin-1 Receptor Antagonists; Prurigo; Pruritus; Visual Analog Scale

The substance P/neurokinin 1 receptor pathway is critical in chronic pruritus; anecdotal evidence suggests that antagonism of this pathway can reduce chronic itch.. To assess the safety and efficacy of the substance P/neurokinin 1 receptor antagonist serlopitant in treating chronic pruritus.. 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.. 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.. The sample size was insufficient for subgroup analyses of the efficacy of serlopitant for chronic pruritus on the basis of underlying conditions.. Serlopitant, 1 mg and 5 mg daily, was associated with a statistically significant reduction in chronic pruritus and was well tolerated (NCT01951274).

Topics: Administration, Oral; Adult; Aged; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Isoindoles; Male; Middle Aged; Neurokinin-1 Receptor Antagonists; Pruritus; Reference Values; Severity of Illness Index; Treatment Outcome

Topics: Humans; Isoindoles; Neurodermatitis; Prurigo; Pruritus