Interpreting the Relationship Among Itch, Sleep, and Work Productivity in Patients with Moderate-to-Severe Atopic Dermatitis: A Post Hoc Analysis of JADE MONO-2

Background: Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis. Objective: The aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial. Methods: A repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep. Results: The relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4–6, and 10 were associated with 0 days, 3–4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0–1, 4–5, and 10 were associated with 0–10%, 20–30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep. Conclusion: These results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity. Clinical Trial Registration: NCT03575871.