LEVEL UP: New Data on Switching from Dupilumab to Upadacitinib in Atopic Dermatitis

Patients with moderate-to-severe atopic dermatitis who failed to adequately respond to dupilumab may attain skin and itch improvements after switching to upadacitinib, new findings suggest.1

These new data were the result of a second period of the LEVEL UP study, authored by such investigators as Christopher Bunick, MD, PhD, associate professor of dermatology at Yale University School of Medicine. In this second LEVEL UP period, Bunick and colleagues built on prior findings from the initial phase of the phase 3b/4 LEVEL UP head-to-head trial.2

The prior analysis suggested upadacitinib use resulted in greater concurrent achievement of near-complete skin clearance and minimal to absent pruritus versus dupilumab after 16 weeks in adults and adolescents with moderate-to-severe disease.

“The current report extends these findings by providing results from period 2 of the LEVEL UP study where patients not achieving ≥ 75% improvement in the Eczema Area and Severity Index (EASI 75) from baseline at the end of period 1 (week 16) entered an additional 16-week treatment period (period 2),” the team wrote.1

Design and Findings on Switching from Dupilumab to Upadacitinib

Individuals who failed to achieve a 75% improvement from baseline at minimum in the Eczema Area and Severity Index (EASI 75) by Week 16 at the conclusion of period 1 of LEVEL UP (NCT05601882) were considered eligible to enter a 16-week extension phase. Bunick and coauthors designated this phase as period 2. In this second phase of LEVEL UP, those who had been treated with dupilumab were switched to upadacitinib at an initial dose of 15 mg. They were given the option to raise their dosage to 30 mg depending on their clinical responses.

Evaluations of efficacy in the second phase of the trial were aimed at greater thresholds of atopic dermatitis control and relief in itch. Assessments included a Worst Pruritus Numerical Rating Scale (WP-NRS) score of 0 or 1, attainment of EASI 90, and the combined achievement of both at the 20 and 32-week marks. There were 208 trial subjects who were transitioned from dupilumab to upadacitinib and entered period 2 of LEVEL UP.

A substantial proportion of these individuals in the extension phase demonstrated, at Week 32, meaningful improvements following the medication switch.1 Bunick and colleagues noted 79.6% reached an EASI 75 score. Additionally, they highlighted the achievement of EASI 90 by 58.7% and EASI 100 by 19.9%. Among study subjects showing a baseline WP-NRS score of 4 at minimum, the investigative team found 60.2% had a reduction of 4 points or more in their level of itch severity.

They found 37.0% of those who entered the second phase with a baseline WP-NRS score exceeding 1 achieved little to no itch, as reflected by a WP-NRS score of 0 or 1.1 In another notable result, the team found 26.8% had met the stringent composite end point of simultaneous EASI 90 and WP-NRS 0/1 by the 32-week mark. Improvements considered clinically meaningful were already evident, according to Bunick et al, at the 20-week mark.1 This result suggested a relatively rapid response after switching medications.

From a safety perspective, a lack of unexpected adverse events (AEs) during this second phase was observed.1 The consistency of the investigators’ safety findings and the established safety profile of upadacitinib was highlighted by Bunick and colleagues. No new safety concerns were identified during the extension phase.

The investigative team highlighted several potential limitations of their research, including noting the study’s limitation “by the absence of a comparator group during period 2 of the Level Up study; measures of improvement are based on a comparison to treatment response following a switch from the comparator group (DUPI) to the treatment group (UPA).”1

References

1. Bunick CG, Magnolo N, Eyerich K, et al. Switching from Dupilumab to Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis After Inadequate Response to Dupilumab: Efficacy and Safety Results from Period 2 of Phase 3b/4 Study (LEVEL UP). Am J Clin Dermatol. 2026 Jan 14. doi: 10.1007/s40257-025-01003-0. Epub ahead of print. PMID: 41533220.

2. Silverberg JI, Bunick CG, Eyerich K. Efficacy and safety of upadacitinib versus dupilumab in adults and adolescents with moderate-to-severe atopic dermatitis: week 16 results of an open-label randomized efficacy assessor-blinded head-to-head phase IIIb/IV study (Level Up). Br J Dermatol. 2024 Dec 23;192(1):36-45. doi: 10.1093/bjd/ljae404. PMID: 39438067.