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Upadacitinib Switch from Dupilumab Effective in Head and Neck Atopic Dermatitis
Investigators assessed the efficacy of switching to upadacitinib in those with atopic dermatitis who had an inadequate response to dupilumab.
Patients with head and neck atopic dermatitis who have inadequate responses to dupilumab and switch to upadacitinib may experience significant improvements in lesions and skin outcomes, according to recent data.1
Upadacitinib, a selective Janus kinase (JAK) 1 inhibitor approved by the US Food and Drug Administration for moderate-to-severe atopic dermatitis in adults and adolescents, has previously been evaluated in head-to-head Level Up and Heads Up clinical trials.2 In this new poster, shown at the 2026 Maui Derm Hawaii meeting, investigators assessed switching to upadacitinib among those with an inadequate response in the head and neck region after dupilumab use.
In this post hoc analysis, the investigative team looked at pooled data from a pair of direct comparison trials assessing upadacitinib versus dupilumab: the LEVEL UP study (NCT05601882) and the HEADS UP study (NCT03738397). those involved in LEVEL UP were initially randomized to be treated either with dupilumab 300 mg or upadacitinib 15 mg. Prior to the beginning of the open-label extension (OLE) at the 16-week mark, subjects on upadacitinib could have their dose raised to 30 mg based on their clinical response.
At week 16 of LEVEL UP, individuals without attainment of adequate disease control, defined as less than 75% improvement in Eczema Area and Severity Index (EASI75), followed different pathways of treatment. Those already given upadacitinib either stayed on their current dose or escalated to a 30 mg dose, while subjects originally assigned to dupilumab switched to upadacitinib 15 mg. They had the option to escalate to upadacitinib 30 mg at the 20-week mark, depending on response to their medication.
In the HEADS UP trial, those evaluated were randomized at the point of baseline to either dupilumab 300 mg or upadacitinib 30 mg, and the OLE phase took place at the 24-week mark. Individuals who completed the double-blind period and chose to continue entered the OLE and were given upadacitinib 30 mg. For those who were dupilumab-treated who also had an inadequate response in the head and neck (HN) region, defined as failure to attain HN EASI75, outcomes were assessed at the 4 and 16-week marks after changing to upadacitinib therapy.
These evaluations were aimed at the proportion of participants reaching HN EASI75, EASI90, and EASI100. Outcomes related to itch, across both studies, were evaluated via the Worst Pruritus Numerical Rating Scale (WP-NRS). The investigators’ analyses included the proportion of subjects who reported a clinically meaningful improvement, defined as at least a 4-point reduction, as well as those achieving minimal or no itch, indicated by WP-NRS scores of 0 or 1. All outcomes related to treatment efficacy were determined through the use of the observed case analyses.
The researchers observed similar baseline demographic and disease characteristics between patients involved in the LEVEL UP and HEADS UP trials. In LEVEL UP, the majority of those evaluated shifting from dupilumab to upadacitinib were successful in attaining HN EASI75, with a substantial proportion also achieving HN EASI90 and EASI100.
Among those who switched, the investigators observed, adjusted median HN EASI scores improved by 87.9% from the point of baseline by 16 weeks after the shifts in treatment. Additionally, the team highlighted comparable results in HEADS UP, where most of those evaluated who switched from dupilumab to upadacitinib attained HN EASI75 and EASI90. Many also reached complete clearance, reflected by EASI100 scores.
In this cohort, adjusted median HN EASI scores were shown to have improved by 97.5% from baseline at 16 weeks post-therapy switch. Across both studies, most of those evaluated experienced clinically meaningful itch severity reductions. Also, a notable proportion reported minimal or no itch within a single month of beginning upadacitinib therapy following the switch from dupilumab.
References
DaSilva D, Shahriari M, Bunick C, et al. Head and Neck Atopic Dermatitis: Therapeutic Response After Switching to Upadacitinib in Moderate-to-Severe Atopic Dermatitis Patients Who Had Inadequate Response to Dupilumab. Presented at: Maui Derm Hawaii 2026; January 25-29, 2026; Maui, Hawaii.
Bunick CG, Irvine AD, Levy GF, et al. Safety of upadacitinib in atopic dermatitis in randomized clinical trials across 6 years. J Eur Acad Dermatol Venereol. 2025 Nov 15. doi: 10.1111/jdv.70172. Epub ahead of print. PMID: 41239921.
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