Upadacitinib Phase 3 Trials Identify Psychological and Functional Benefits of Ambitious Treatment Targets in AD

A post hoc analysis of the phase 3 Measure Up 1 and Measure Up 2 trials provides new evidence that achieving more stringent treatment targets in moderate to severe atopic dermatitis (AD) is associated with substantially greater improvements in patient-reported outcomes (PROs).¹ With this research, the authors reinforce the clinical relevance of treat-to-target strategies such as those proposed by the Aiming High in Eczema/Atopic Dermatitis (AHEAD) recommendations.²

Background

While traditional clinical trial endpoints in AD have focused on physician-assessed measures such as the Eczema Area and Severity Index (EASI), there is increasing recognition that patient-centered outcomes are critical to evaluating treatment success. The AHEAD framework emphasizes the importance of aiming for optimal disease control—defined by near-complete skin clearance and minimal itch—through shared decision-making between clinicians and patients.

Study Design

In this poster, presented at the 2026 American Academy of Dermatology Annual Meeting, investigators pooled data from 2 randomized, double-blind, placebo-controlled phase 3 trials evaluating oral upadacitinib (15 mg or 30 mg daily) in adolescents and adults with moderate to severe AD. Patients were stratified into mutually exclusive cohorts based on treatment response at week 16, regardless of assigned therapy. The “optimal” target was defined as achieving at least 90% improvement in EASI (EASI 90) along with minimal itch (Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0 or 1). The “moderate” target was defined as EASI 75 with a ≥4-point improvement in WP-NRS, while a third group included patients who achieved neither threshold.

The analysis evaluated the proportion of patients in each cohort who achieved stringent PRO targets at week 16 across multiple domains, including quality of life, symptom burden, sleep, pain, psychological health, daily functioning, and treatment satisfaction. These outcomes were assessed using validated instruments such as the Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), Atopic Dermatitis Symptom Scale (ADerm-SS), and Atopic Dermatitis Impact Scale (ADerm-IS).

Results

The findings demonstrated a clear gradient of benefit, with patients achieving the optimal skin and itch target experiencing the greatest improvements across all PRO measures. At week 16, those in the optimal group were substantially more likely to report no or minimal impact of AD on quality of life, as reflected by DLQI or children’s DLQI scores of 0 or 1. Similarly, a higher proportion achieved POEM scores indicative of clear or almost clear disease, as well as minimal symptom burden on ADerm-SS.

Sleep outcomes also showed marked improvement among patients achieving optimal targets. A significantly greater proportion reported minimal or no sleep disturbance based on both Sleep NRS and ADerm-IS sleep domain scores compared with those in the moderate group. Improvements in skin pain followed a similar pattern, with more patients in the optimal cohort reporting little to no pain.

Importantly, the benefits extended beyond physical symptoms to psychological outcomes. Patients achieving optimal targets were more likely to experience meaningful improvements in anxiety and depression, as measured by HADS scores, highlighting the broader psychosocial impact of achieving near-complete disease control. Functional outcomes also improved as greater proportions of patients reported minimal interference with their daily activities and emotional well-being.

Treatment satisfaction was also notably higher in the optimal cohort. Approximately 82% of patients achieving EASI 90 and WP-NRS 0/1 reported being very or extremely satisfied with their treatment, compared with 68.6% of those achieving the moderate target.

Final Thoughts

Overall, the findings reinforce the AHEAD recommendations and support a shift toward more ambitious treatment goals in AD management, emphasizing the value of targeting near-complete clearance and minimal symptoms whenever feasible. Incorporating PROs into routine assessment may further help clinicians tailor therapy and monitor treatment success from the patient’s perspective, as the authors noted.

References

1. Kirchhof M, Bunick C, Savage L, et al. Impact of Optimal vs Moderate Skin and Itch Treatment Targets on Patient-Reported Outcomes in Moderate-to-Severe Atopic Dermatitis: Insights from Measure Up 1 and 2 Phase 3 Studies. Poster presented at: 2026 American Academy of Dermatology Annual Meeting; March 27-31, 2026; Denver, Colorado.

2. Silverberg JI, Gooderham M, Katoh N, et al. Combining treat-to-target principles and shared decision-making: International expert consensus-based recommendations with a novel concept for minimal disease activity criteria in atopic dermatitis. J Eur Acad Dermatol Venereol. 2024;38(11):2139-2148. doi:10.1111/jdv.20229