Worst Itch Numeric Rating Scale Effective as Fit-for-Purpose Instrument for Prurigo Nodularis

New findings suggest that the Worst Itch Numeric Rating Scale (WI-NRS) may be a fit-for-purpose tool which supports the efficacy end points assessing pruritus intensity among adults with prurigo nodularis (PN).¹

These findings were the conclusion of new research, led by Shawn Kwatra, MD, of Johns Hopkins Medical Institutions in Baltimore, Maryland. Kwatra et al. sought to evaluate the WI-NRS tool’s clinically meaningful thresholds for itch improvement and validate psychometric properties for WI-NRS among individuals with moderate to severe prurigo nodularis.

The investigators noted the psychometric properties of WI-NRS had been well-researched in terms of use in dermatologic diseases such as psoriasis and eczema, though they concluded that evidence for use in prurigo nodularis had been limited.²

“This study aimed to evaluate the content validity of WI-NRS through qualitative interviews,” Kwatra and colleagues wrote. “Assessment of the psychometric properties and a confirmation of the within-patient improvement thresholds for the WI-NRS instrument was done using data from recent phase 3 PN trials.”

Background and Methods

The research team had previously carried out the PRIME and PRIME2 studies, and their new secondary analysis centered on the content validity of the WI-NRS assessment tool. They implemented in-depth, one-on-one qualitative interviews with a total of 20 individuals who had prurigo nodularis patients in the US.

There were 3 such patients in New Orleans, 10 in Los Angeles, and 7 in St. Louis. The investigators used concept elicitation and cognitive debriefing techniques for their interviews of these participants.

The subjects were determined based upon a set of inclusion criteria: maintaining a confirmed diagnosis of prurigo nodularis with or without mild atopic dermatitis (an Investigator’s Global Assessment [IGA] Scale score of 2 for 3 months at least), being 18 years or older, and having been willing to provide informed consent.

In their secondary analysis of the PRIME and PRIME2 studies, the research team’s assessments of content validity of WI-NRS involved psychometric evaluations which drew from pooled data from masked, intention-to-treat (ITT) patients with prurigo nodularis. The patients had been from double-masked, randomized, and placebo-controlled studies.

The team’s evaluations included construct validity, test-retest reliability, known-groups validity, and sensitivity to alterations in adult individuals with moderate-to-severe disease. They found thresholds for substantial within-subject improvement in WI-NRS scores by utilizing both distribution and anchor-based methods.

The investigators’ assessment was done following each of the PRIME and PRIME2 studies’ conclusions. Specifically, December 2019 - November 2021 for PRIME and January 2020 - August 2021 for PRIME2.

The exposures assessed by the team were dupilumab (300 mg) or placebo administered subcutaneously every 2 weeks for a total of 24 weeks. The major outcomes they evaluated were WI-NRS scores at specified time points up to 24 weeks after randomization.

Findings

There were a total of 20 subjects in the 2 studies analyzed, with the average age of these participants being 49.3 years and 55% being female. There were 311 individuals involved in the combined intention-to-treat assessment, with average age being 49.5 years and 65.3% being female.

The investigators found that among those with prurigo nodularis, the WI-NRS questions among all 20 subjects, the recall period among 19 of 20, and the response scale among all 20 had been found to be clear and pertinent. They also reported that the test-retest reliability of the tool between the points of screening and baseline had been sufficient, with intraclass correlation coefficient being 0.72, using Patient Global Impression of Severity [PGIS] for stable participants.

The research team confirmed WI-NRS’s validity through correlations which were rated as moderate to strong (absolute r range = 0.34-0.73) with related measures and rated as weaker (absolute r range = 0.06-0.32) with less related measures. The assessment tool was also shown to be responsive to changes, which the team noted was indicated by variations in groups’ baseline changes (per PGIS change and PGI of Change [PGIC]).

The investigators also noted that the threshold for improvements deemed to be clinically meaningful had been 4 points (range, 3.0-4.5). This was based upon anchor-based methods with PGIC and PGIS, corroborated by the use of distribution-based methods.

“The WI-NRS was found to be a valid and reliable instrument to capture itch data of patients with PN, and a 4-point improvement on WI-NRS may be used to represent a within-patient meaningful improvement in patients with PN,” they wrote. “WI-NRS is a fit-for-purpose instrument to support efficacy end points measuring the intensity of itching in adults with PN.”

References

1. ^{Kwatra SG, Yosipovitch G, Kim B, et al. Worst Itch Numeric Rating Scale for Prurigo Nodularis: A Secondary Analysis of 2 Randomized Clinical Trials. JAMA Dermatol. Published online June 12, 2024. doi:10.1001/jamadermatol.2024.1634.}
2. ^{Naegeli AN, Flood E, Tucker J, Devlen J, Edson-Heredia E. The Worst Itch Numeric Rating Scale for patients with moderate to severe plaque psoriasis or psoriatic arthritis. Int J Dermatol. 2015;54(6):715-722. doi:10.1111/ijd.12645.}