Validation of a scoring algorithm for the clinician-reported outcome tool 'prurigo activity and severity (PAS)' based on clinical studies of dupilumab in adults with prurigo Nodularis.

Background: Prurigo nodularis (PN) also known as chronic prurigo, is a chronic inflammatory skin disease characterized by intensely itchy nodules/lesions which occur due to intensive scratching. PN management is, in part, based on clinician evaluations of PN lesions, which can be supported by clinician-reported outcomes (ClinRO) such as the Prurigo Activity and Severity (PAS) instrument. A 5-item version of PAS was included in recent phase-3 dupilumab PN trials (PRIME [NCT04183335]/PRIME2 [NCT04202679]). The PAS score was derived using the unweighted sum of 3-items of the 5-item PAS (range, 0-11; higher score indicates worse activity and severity): Item 2 (number of lesions), Item 5a (percentage of lesions with excoriations/crusts) and Item 5b (percentage of healed lesions) for use in clinical practice and for communication of treatment benefit to physicians.

Objectives: To evaluate the measurement properties of PAS score and derive within-patient (responder definition) and between-group improvement thresholds for interpreting changes in PAS score in patients with PN.

Methods: The data source was the pooled treatment group, intention-to-treat (ITT) data from the phase-3 PRIME (NCT04183335) and PRIME2 (NCT04202679) studies evaluating the efficacy of dupilumab in adult patients with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. PAS score reliability, validity and sensitivity to change were evaluated, and anchor- and distribution-based methods were applied to derive meaningful change thresholds.

Results: The pooled ITT population included 311 patients (mean age 49.5 years, 65.3% female). Adequate to good psychometric properties were demonstrated for PAS score. The within-patient meaningful improvement threshold was estimated as 3.0 points (absolute change) and 37% (per cent change). A 1.7-point (absolute change) and 20% (per cent change) improvement were estimated to reflect a between-group meaningful change in PAS score.

Conclusions: PAS score is a simple, clinically relevant indicator of PN lesion activity and severity supported by suitable psychometric performance.