Background

The Itch Numeric Rating Scale (NRS), Skin Pain NRS, and Atopic Dermatitis Sleep Scale (ADSS) are self-administered patient-reported outcome (PRO) instruments developed to assess symptoms in patients with atopic dermatitis (AD). The objective of this study was to evaluate the psychometric properties (reliability, validity, and responsiveness) and interpretability thresholds of these PROs using data from three pivotal Phase 3 studies in adults.

Methods

BREEZE-AD1, BREEZE-AD2, and BREEZE-AD5 evaluated the safety and efficacy of baricitinib in adults with moderate-to-severe AD. Clinician-reported outcomes and other PROs commonly assessed in patients with AD were used to estimate meaningful changes and evaluate test-retest reliability, convergent and divergent validity, known-groups validity, responsiveness, and meaningful change thresholds (MCTs) of the Itch NRS, Skin Pain NRS, and ADSS.

Results

The test-retest reliability of the Itch NRS, Skin Pain NRS, and ADSS was evidenced by generally large intraclass correlation coefficients (> 0.7) in stable groups of patients between baseline and Week 1 and Weeks 4 and 8. Moderate-to-large correlations (r > 0.4) at baseline and Week 16 were generally observed between each measure and other PROs measuring the same concept, supporting convergent validity. Small-to-moderate correlations with clinician-reported outcomes demonstrated divergent validity. Each instrument was able to distinguish between known groups of disease severity as assessed using other indicators of AD severity. The responsiveness of the Itch NRS, Skin Pain NRS, and ADSS scales was demonstrated through significant differences in their change scores from baseline to Week 16 between categories of change in another PRO also from baseline to Week 16. Thresholds for interpreting meaningful change were estimated as - 4.0 for the 0-10 Itch and Skin Pain NRS items; - 1.25 for the 0-4 ADSS Items 1 and 3 and; - 1.50 for the 0-29 ADSS Item 2, these equivalent to moderate degrees of change.

Conclusions

Results of this study demonstrate that the psychometric properties of the Itch NRS, Skin Pain NRS, and ADSS are good to excellent. These findings support the use of these instruments in daily assessment of AD symptoms in adults with moderate-to-severe AD. Trial registration ClinicalTrials.gov numbers: NCT03334396, NCT03334422, and NCT03435081.

Background

The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) is a standardized severity assessment for use in clinical trials and registries for atopic dermatitis (AD).

Objectives

To investigate the reliability, validity, responsiveness and within-patient meaningful change of the vIGA-AD.

Methods

Data were analysed from adult patients with moderate-to-severe AD in the BREEZE-AD1 (N = 624 patients; NCT03334396), BREEZE-AD2 (N = 615; NCT03334422) and BREEZE-AD5 (N = 440; NCT03435081) phase III baricitinib clinical studies.

Results

Across studies, test-retest reliability for stable patients showed moderate-to-good agreement [range of Kappa values for Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD), 0·516-0·639; for Eczema Area and Severity Index (EASI), 0·658-0·778]. Moderate-to-large correlations between vIGA-AD and EASI or body surface area (range at baseline, 0·497-0·736; Week 16, 0·716-0·893) supported convergent validity. Known-groups validity was demonstrated vs. EASI and PGI-S-AD (vIGA-AD for severe vs. moderate EASI categories at baseline, P < 0·001). Responsiveness was demonstrated vs. EASI (P < 0·001 for much improved vs. improved and improved vs. stable). Anchor- and distribution-based methods supported a vIGA-AD change of -1·0 as clinically meaningful. These findings are limited to populations defined by the studies' inclusion and exclusion criteria.

Conclusions

The vIGA-AD demonstrated sufficient reliability, validity, responsiveness and interpretation standards for use in clinical trials. What is already known about this topic? A description of the development of the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) has been published previously. What does this study add? The current study validates the vIGA-AD by demonstrating appropriate test-retest reliability, convergent validity, known-groups validity and responsiveness across three baricitinib clinical studies. In addition, a 1-point change was identified as a clinically meaningful patient-perceived change minimal clinically important difference in the vIGA-AD. What are the clinical implications of the work? The vIGA-AD is a measure for investigator assessment of atopic dermatitis suitable for use in clinical research.