OBJECTIVES: A phase 3 clinical trial (NCT04681729) was conducted to evaluate the efficacy and safety of dupilumab among Chronic Inducible Cold Urticaria (ColdU) patients, using several single-item patient reported outcome measures (PROMs) after ice cube application to inform efficacy endpoints: Peak Pruritus-Numeric Rating Scale (PP-NRS), Peak Pain-NRS, and Peak Burning Sensation-NRS (PBS-NRS). Each item is rated on a scale from 0 (no symptom) to 10 (worst symptom severity). Psychometric properties of the three NRSs were assessed using data from the trial.

METHODS: A total of 82 ColdU patients were randomized. The psychometric analyses included construct validity, reliability, and responsiveness; within-patient and between-group meaningful change thresholds (MCTs) were estimated using Patient Global Impression of Change/Severity (PGIC/S) as anchors.

RESULTS: The baseline mean score for PP-NRS, Peak Pain-NRS and PBS-NRS were 6.47, 5.62 and 5.85, respectively. The three NRSs scales demonstrated a near to adequate test-retest reliability (interclass correlation coefficient ranges from 0.56 to 0.68) and an adequate convergent validity (moderate to strong correlation for both PP-NRS and PBS-NRS with several measures, including PGIS, and low to strong correlation for Peak Pain-NRS with the same measures). All scales demonstrated known-groups validity and were sensitive to detect change (all p<0.05). MCTs were estimated for within-patient (PP-NRS: 4, range: 3-6; Peak Pain-NRS: 3, range: 2-3 and PBS-NRS: 3, range: 2-5) and between-group (PP-NRS: 2.7, range: 2.5-3.3; Peak Pain-NRS: 2.2, range: 1.6-3.2 and PBS-NRS: 2.7, range: 1.6-3.4), respectively.

CONCLUSIONS: The findings demonstrate acceptable psychometric properties of the three NRSs under investigation and support their ability to capture meaningful change in symptoms experienced by the ColdU patients in a clinical trial context.