Upadacitinib Switch Linked to No Skin Flares in Atopic Dermatitis

Patients with moderate to severe atopic dermatitis (AD) had no skin lesion flares through 16 weeks after switching to upadacitinib (Rinvoq; AbbVie) following an inadequate response to dupilumab (Dupixent; Regeneron and Sanofi). The finding comes from a post hoc analysis of the LEVEL UP and HEADS UP trials, presented in a poster at the 2026 Fall Clinical Dermatology Conference in Las Vegas, Nevada. Itch flares were infrequent in both studies.¹

According to the study authors, patient concerns about losing partial disease control or experiencing worsening symptoms can complicate treatment-switch decisions after an inadequate response to a biologic. Upadacitinib, an oral Janus kinase inhibitor, showed superior efficacy over dupilumab, an IL-4 receptor alpha antagonist, in the head-to-head HEADS UP and LEVEL UP trials.^2,3

The analysis included patients who switched from dupilumab to upadacitinib monotherapy in LEVEL UP (NCT05601882) and HEADS UP (NCT03738397). Inadequate response was defined as failure to achieve at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI) score (EASI 75). In LEVEL UP, patients with an inadequate response to dupilumab 300 mg at week 16 switched to upadacitinib 15 mg, with escalation to 30 mg based on clinical response.¹

In HEADS UP, the analysis focused on patients who did not achieve EASI 75 at week 24 and then switched to upadacitinib, and patients who reached EASI 75 were excluded. The LEVEL UP cohort included 207 patients, and the HEADS UP cohort included 28. At the time of switching, mean EASI scores were 13.5 (SD, 7.7) in LEVEL UP and 11.8 (SD, 4.6) in HEADS UP.¹

Mean Worst Pruritus Numerical Rating Scale (WP-NRS) scores at the switch were 3.9 (SD, 2.3) in LEVEL UP and 4.1 (SD, 2.7) in HEADS UP. Skin lesion flare was defined as an increase of at least 6.6 points in EASI score from the time of switching. Through 16 weeks, no skin lesion flares occurred in LEVEL UP (0/201) or HEADS UP (0/27), based on observed case data.¹

Itch Flares and Dose Escalation Data

Itch flare was defined as an increase of at least 4 points in WP-NRS score from the time of switching. A 4-point increase cannot occur from a score above 6 on the 0-to-10 scale. The itch flare analysis was therefore limited to patients with a WP-NRS score of 6 or lower at the switch.¹

Patients with 1 or more itch flares at any visit were counted once. Itch flares occurred in 3.6% (5/139) of patients in LEVEL UP and 4.8% (1/21) of patients in HEADS UP. In LEVEL UP, 52.7% of the 207 patients who switched to upadacitinib 15 mg remained on this dose without escalation.¹

In LEVEL UP, EASI was assessed at weeks 4 and 16 after the switch, and itch results relied on weekly averages from weeks 1 to 16. In HEADS UP, EASI and WP-NRS were assessed at weeks 4, 8, and 16.¹ The poster did not report safety data for the switch population.¹

The authors concluded the findings may help inform treatment-switch discussions with patients concerned about worsening skin lesions or itch during the transition from dupilumab to upadacitinib. The analysis was post hoc, and HEADS UP contributed a small subgroup of 28 patients.¹

References

1. Zirwas MJ, Ruiz Dasilva D, Shahriari M, et al. Switching to upadacitinib monotherapy was associated with minimal or no flares following inadequate response to dupilumab in patients with moderate-to-severe atopic dermatitis. Presented at: The 2026 Fall Clinical Dermatology Conference; October 8–11, 2026; Las Vegas, NV. Poster DV-021148.
2. Blauvelt A, Teixeira HD, Simpson EL, et al. Efficacy and safety of upadacitinib vs dupilumab in adults With moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2021;157(9):1047-1055. doi: 10.1001/jamadermatol.2021.3023
3. Silverberg JI, Bunick CG, Hong HC, et al. 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;192(1):36-45. doi: 10.1093/bjd/ljae404