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Clinical Trial
. 2024 Aug 1;160(8):813-821.
doi: 10.1001/jamadermatol.2024.1634.

Worst Itch Numeric Rating Scale for Prurigo Nodularis: A Secondary Analysis of 2 Randomized Clinical Trials

Shawn G Kwatra  1 , Gil Yosipovitch  2 , Brian Kim  3 , Sonja Stander  4 , Stephanie Rhoten  5 , Cristina Ivanescu  5 , Nadine Haeusler  5 , Ella Brookes  6 , Jerome Msihid  7 , Melanie Makhija  6 , Ashish Bansal  8 , Ryan B Thomas  8 , Donia Bahloul  7
Affiliations
Clinical Trial

Worst Itch Numeric Rating Scale for Prurigo Nodularis: A Secondary Analysis of 2 Randomized Clinical Trials

Shawn G Kwatra et al. JAMA Dermatol. .

Abstract

Importance: Prurigo nodularis (PN) is a debilitating skin disease characterized by the hallmark symptom of chronic itch; the intensity of itch in PN was assessed using the Worst Itch Numeric Rating Scale (WI-NRS) to evaluate the primary efficacy end point of 2 recent phase 3 studies of dupilumab treatment for PN.

Objective: To validate the psychometric properties and to determine the clinically meaningful improvement threshold for WI-NRS in patients with moderate to severe PN.

Design, setting, and participants: In this secondary analysis of the PRIME and PRIME2 trials, content validity of WI-NRS was assessed through in-depth patient interviews. Psychometric assessments used pooled data from masked, intention-to-treat (ITT) patients with PN from randomized, double-masked, and placebo-controlled studies. Psychometric assessments included test-retest reliability, construct validity, known-groups validity, and sensitivity to change in adult patients with moderate-to-severe PN. Thresholds for meaningful within-patient improvement in the WI-NRS score were determined using anchor and distribution-based approaches. Data were analyzed after completion of each study, December 2019 to November 2021 for PRIME and January 2020 to August 2021 for PRIME2.

Exposures: Dupilumab (300 mg) or placebo subcutaneously every 2 weeks for 24 weeks.

Main outcomes and measures: WI-NRS score at specified time points up to 24 weeks after randomization.

Results: A total of 20 patients were included across the 2 studies (mean [SD] age, 49.3 [17.2] years; 11 female [55%]); 311 patients were included in the pooled intention-to-treat analysis (mean [SD] age, 49.5 [16.1] years; 203 female [65.3%]). The WI-NRS questions (20 of 20 patients), recall period (19 of 20 patients), and response scale (20 of 20 patients) were easy to understand and relevant for patients with PN. Adequate test-retest reliability was observed between screening and baseline (intraclass correlation coefficient = 0.72, using Patient Global Impression of Severity [PGIS] to define stable patients). Convergent and discriminant validity was supported by moderate to strong correlations (absolute r range = 0.34-0.73) with other conceptually related measures and weaker correlations (absolute r range = 0.06-0.32) with less-related measures, respectively. WI-NRS was sensitive to change, as demonstrated by differences in change from baseline among groups (per PGIS change and PGI of Change [PGIC]). Using anchor-based approach with PGIS and PGIC, the clinically meaningful improvement threshold was 4 points (range, 3.0-4.5), which was also supported by distribution-based methods.

Conclusion and relevance: This study found that WI-NRS may be a fit-for-purpose instrument to support efficacy end points measuring the intensity of itching in adults with PN.

Trial registration: NCT04183335 (PRIME) and NCT04202679 (PRIME2).

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kwatra reported receiving personal fees from Sanofi and Regneron outside the submitted work; he is an advisory board member and/or consultant for AbbVie, Amgen, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Bristol Myers Squibb, Cara Therapeutics, Dermavant, Galderma, Incyte Corporation, Johnson & Johnson, Leo Pharma, Novartis Pharmaceuticals Corporation, Pfizer, Regeneron Pharmaceuticals, and Sanofi and has served as an investigator for Galderma, Incyte, Pfizer, and Sanofi. Dr Yosipovitch reported personal fees and grants from Sanofi Regeneron during the conduct of the study; he reported receiving grants for work as an investigator from Eli Lilly, Pfizer, Novartis, Escient, LEO, Celldex, and Kiniksa outside the submitted work; he received personal fees from Galderma for service as advisory board member and an investigator, AbbVie as an investigator and advisory board member, GSK as an advisory board member, Eli Lilly as an investigator and advisory board member, Pfizer as an advisory board member, Novartis as an advisory board member, Arcutis as an advisory board member, Vifor for consulting work, Kamari for consulting work, and nonfinancial support from Piere Fabre as an investigator; he also served as a member of boards for International Forum for the Study of Itch, National Psoriasis Foundation, and International Eczema Council. Dr Kim reported receiving nonfinancial support preparing the manuscript from Sanofi Regeneron during the conduct of the study; he reported receiving personal fees from 23andMe, ABRAX Japan, AbbVie, Almirall, Amgen, Arcutis Biotherapeutics, Arena Pharmaceuticals, argenx, AstraZeneca, Boehringer Ingelheim, BristolMyers Squibb, Cara Therapeutics, Clexio Biosciences, Eli Lilly and Company, Escient Pharmaceuticals, Evommune, Galderma, Genentech, GSK, Granular Therapeutics, Incyte Corporation, Innovaderm Research, Janssen, Kiniksa, LEO Pharma, Micreos, Novartis, Pfizer, Recens Medical, Regeneron Pharmaceuticals, Sanofi, Septerna, Teva, Trevi, Triveni, Vial, and WebMD outside the submitted work; in addition, Dr Kim had a patent for Janus kinase inhibitors for itch issued. Dr Ständer reported grants from Sanofi, Galderma, Kiniksa Pharmaceuticals, and Trevi Therapeutics outside the submitted work; she reported receiving personal fees and/or support to her institution from Sanofi, Galderma, Celldex, Incyte, Kiniksa Pharmaceuticals, Trevi Therapeutics, Eli Lilly, AbbVie, and Amgen outside the submitted work. Dr Rhoten reported personal fees from IQVIA during the conduct of the study; she reported personal fees from IQVIA outside the submitted work. Dr Ivanescu contract work with IQVIA to perform the analyses during the conduct of the study. Dr Haeusler reported receiving personal fees from Sanofi during the conduct of the study. Dr Msihid reported employment and stock option ownership with Sanofi during the conduct of the study. Dr Bansal reported employment with Regeneron Pharmaceuticals during the conduct of the study. Dr Thomas reported employment and ownership of stock options with Regeneron Pharmaceuticals during the conduct of the study. Dr Bahloul reported personal fees from Sanofi during the conduct of the study. No other disclosures were reported.

Comment on

References

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