Peak Pruritus Numerical Rating Scale: psychometric validation and responder definition for assessing itch in moderate‐to‐severe atopic dermatitis

Abstract

SummaryBackgroundModerate‐to‐severe atopic dermatitis (AD) is a chronic disease characterized by intense, persistent and debilitating itch, resulting in sleep deprivation, signs of anxiety and depression, impaired quality of life and reduced productivity. The Peak Pruritus Numerical Rating Scale (NRS) was developed and validated as a single‐item, patient‐reported outcome (PRO) of itch severity.ObjectivesTo describe the content validity and psychometric assessment (test–retest reliability, construct validity, known‐groups validity, sensitivity to change) of the Peak Pruritus NRS, and to derive empirically a responder definition to identify adults with a meaningful change in itch.MethodsContent validity was assessed through in‐depth patient interviews. Psychometric assessments used data from phase IIb and phase III dupilumab clinical trials and included test–retest reliability, construct validity, known‐groups validity and sensitivity to change in patients with moderate‐to‐severe AD.ResultsInterview participants indicated that the Peak Pruritus NRS was a relevant, clear and comprehensive assessment of itch severity. Peak Pruritus NRS scores showed large, positive correlations with existing PRO measures of itch, and weak or moderate correlations with clinician‐reported measures assessing objective signs of AD. Peak Pruritus NRS score improvements were highly correlated with improvements in other itch PROs, and moderately correlated with improvements in clinician‐reported measures assessing objective signs of AD. The most appropriate threshold for defining a clinically relevant, within‐person response was ≥ 2–4‐point change in the Peak Pruritus NRS.ConclusionsThe Peak Pruritus NRS is a well‐defined, reliable, sensitive and valid scale for evaluating worst itch intensity in adults with moderate‐to‐severe AD.

Clinically Meaningful Responses to Dupilumab in Adolescents with Uncontrolled Moderate-to-Severe Atopic Dermatitis: Post-hoc Analyses from a Randomized Clinical Trial

“…Patients in the FAS and the IGA > 1 subgroup had statistically significant improvements from baseline (nominal p < 0.05) as early as 1-2 weeks in EASI, SCORAD score, BSA affected, itch (Peak Pruritus NRS and SCORAD pruritus VAS scores), SCORAD sleep VAS score, POEM score, CDLQI, and the Patient Global Assessment of Disease Severity category; they also experienced less breakthrough disease, as assessed by the use of rescue medication for intolerable symptoms, compared with patients who received placebo. More dupilumab-treated patients in both analysis populations had significant improvements in several outcome measures with pre-specified thresholds for clinical importance, including EASI-50 [26,33] and EASI-75, ≥ 3-point improvement in Peak Pruritus NRS score [34,35], and ≥ 6-point improvement in both POEM score [33,36] and CDLQI [36]. Significantly more dupilumab-than placebo-treated patients in the FAS and IGA > 1 subgroup had an absolute EASI ≤ 7 or CDLQI ≤ 6 at week 16, indicating that they had, at worst, mild disease by the end of treatment [37,38].…”

“…Such a definition of treatment response would be more relevant for clinical decision making than one based on IGA alone. Therefore, clinically meaningful improvements are defined here as improvements from baseline of ≥ 50% in EASI [26,33], ≥ 3 points in the Peak Pruritus Numerical Rating Scale (NRS) score [34,35], or ≥ 6 points in the Children's Dermatology Life Quality Index (CDLQI) [36], values based on published thresholds of clinically meaningful improvements.…”

“…Clinically meaningful improvement in at least one of the three domains of signs, symptoms, and QoL was defined as EASI-50, ≥ 3-point improvement in Peak Pruritus NRS score from baseline, ≥ 6-point improvement in POEM score from baseline, or ≥ 6-point improvement in CDLQI from baseline at week 16. Improvement thresholds for EASI [26,33], Peak Pruritus NRS score [34,35], POEM score [33,36], and CDLQI [36] were based on the published minimal clinically important differences in the population of adolescents with AD. We also assessed the proportions of patients with EASI ≤ 7 at week 16, a category that corresponds to mild AD [37], and with CDLQI ≤ 6, a category indicating no or a small impact on QoL [38].…”

A New Generation of Treatments for Itch

“…Dupilumab is a monoclonal antibody targeting the α subunit of the IL-4 receptor, blocking the signaling of cytokines IL4 and IL13, key cytokines involved in T helper (Th) 2 immunity. Dupilumab has revolutionized the treatment of AD, significantly improving clinical symptoms of AD, rapidly reducing itch, and improving patients' quality of life (33,34). Currently, the use of dupilumab in other pruritic con ditions is of great interest.…”

Clinical Response and Quality of Life in Patients with Severe Atopic Dermatitis Treated with Dupilumab: A Single-Center Real-Life Experience

“…Response to dupilumab was defined as an improvement of ≥75% in EASI from baseline (EASI75). Additionally, patient-reported outcomes including the Italian version of Dermatology Life Quality Index (DLQI) questionnaire [20], Patient-Oriented Eczema Measure (POEM) [21], Hospital Anxiety and Depression Scale (HADS) [22], Peak Pruritus Numerical Rating Scale (NRS-itch) during the past 7 days [23], and VAS-sleep [24], which are measurement instruments widely accepted to evaluate quality of life in AD, were collected at baseline and at weeks 4 and 16 after dupilumab initiation.…”