Efficacy of Abrocitinib and Dupilumab in Patients With Moderate-to-Severe Atopic Dermatitis With Severe Itch at Baseline and in Subgroups by Baseline Thresholds of Severe Itch: A Post Hoc Analysis of the JADE COMPARE and JADE DARE Clinical Trials

INTRODUCTION • Itch associated with atopic dermatitis (AD) has a substantial impact on the patient’s quality of life1 • Patients with moderate-to-severe AD often describe itch as their most burdensome symptom2 • Abrocitinib, an oral Janus kinase-1-selective inhibitor, provided significantly greater itch responses at week 2 of treatment compared with dupilumab, an injectable interleukin-4 receptor alpha inhibitor, in patients with moderate-to-severe AD who received background topical therapy in 2 randomized clinical trials3,4 • Efficacy of abrocitinib and dupilumab has not been investigated in patients with AD and severe itch OBJECTIVE • To evaluate the efficacy of abrocitinib and dupilumab in patients with moderate-to-severe AD and severe itch using various baseline thresholds of severe itch METHODS Study Design • This post hoc analysis included data from patients with moderate-to-severe AD who received abrocitinib 200 mg QD or dupilumab 300 mg Q2W in combination with background topical therapy in the JADE COMPARE (NCT03720470) and JADE DARE (NCT04345367) phase 3 trials (Supplementary Figure) • Patients from JADE COMPARE and JADE DARE who had severe itch at baseline (Peak Pruritus Numerical Rating Scale [PP-NRS, used with permission from Regeneron Pharmaceuticals, Inc. and Sanofi] score ≥7) were pooled for analysis Analyses • All patients having baseline PP-NRS ≥7, as well as individual subgroups with baseline PP-NRS scores of 7, 8, 9, and 10, were assessed at week 2 and week 16 for achievement of ≥4-point improvement in PP-NRS (PP-NRS4), PP-NRS score of 0 or 1 (itch-free state), and Dermatology Life Quality Index score of 0 or 1 (DLQI 0/1) • Patient-Oriented Eczema Measure (POEM) score of ≤2 was assessed at week 16 • Missing data were handled using nonresponder imputation, whereby if a subject withdrew from the study, they were considered nonresponders after withdrawal RESULTS Patients and Baseline Disease Characteristics • A total of 875 patients had severe itch at baseline (abrocitinib 200 mg, 453; dupilumab 300 mg, 422) • Overall, patients had substantial itch (median PP-NRS: 8 [abrocitinib] and 8 [dupilumab]) and quality of life impairment (median DLQI: 16 [abrocitinib] and 16 [dupilumab]) at baseline • Baseline disease characteristics for the overall pooled population and individual subgroups by baseline PP-NRS scores are shown in Table 1 — Subgroups with baseline PP-NRS score of 9 or 10 were associated with greater baseline disease severity — Similarly, median DLQI scores at baseline were greater in subgroups with baseline PP-NRS scores of 9 or 10 than those with baseline PP-NRS scores of 7 or 8 Itch Response and Patient-Reported Outcomes by Baseline Itch Severity • The proportions of patients achieving PP-NRS4 and PP-NRS 0/1 at week 2 were greater with abrocitinib than with dupilumab in patients with severe itch, regardless of the baseline threshold; by week 16, the relative differences between treatment groups diminished for PP-NRS4 but were maintained for PP-NRS 0/1 (Figure 1) • The proportions of patients achieving POEM ≤2 response at week 16 were greater with abrocitinib than dupilumab across all evaluated thresholds of severe itch (Figure 2) • A greater proportion of patients achieved DLQI 0/1 response with abrocitinib than dupilumab at week 2 which was maintained at week 16 across all evaluated thresholds of severe itch (Figure 2). CONCLUSIONS • Patients with moderate-to-severe AD who had a higher burden of itch at baseline reported a greater impairment in patient-reported measures of quality of life and disease severity • Across various thresholds of severe itch, abrocitinib provided more rapid achievement of an itch-free state (defined as PP-NRS 0/1) and substantial quality of life improvements that were greater than dupilumab as early as the first assessment at week 2 • The difference between abrocitinib and dupilumab treatment groups largely diminished by week 16 for PP-NRS4 but was maintained for PP-NRS 0/1, POEM ≤2, and DLQI 0/1, suggesting a 4-point improvement in PP-NRS may not be sufficient for patients with severe itch at baseline • Abrocitinib may be an appropriate treatment option for patients who have severe itch and are expecting to achieve an itch-free state.