Dose Escalation to Upadacitinib 30 mg Necessary Among Some with Atopic Dermatitis

Data presented at the American Academy of Dermatology (AAD) Annual Meeting demonstrate that targeting multiple disease pathways is necessary for attaining high efficacy among those with atopic dermatitis, and the mechanistic rationale supports raising upadacitinib doses to 30mg for certain patients to reach an Eczema Area and Severity Index (EASI) 90 response.1

These data were the result of a recent analysis authored, in part, by Kilian Eyerich, MD, PhD, chair and professor at the department of dermatology and venerology for the University of Freiburg, Germany. The results were drawn from a biomarker analysis of the LEVEL-UP trial (NCT05601882) and were presented at AAD in Orlando.

Eyerich noted that the analysis’s goal had been to “elucidate molecular mechanisms driving the superior treatment response to upadacitinib over dupilumab in patients with moderate-to-severe atopic dermatitis using biomarker analyses.”1

Atopic dermatitis is an inflammatory skin condition that is characterized by impairments to patients’ skin barrier and by multifactorial immune dysregulation. Both upadacitinib and dupilumab are medications which have been approved by the US Food and Drug Administration (FDA), with the former having superior efficacy in recent clinical findings.2

Such findings, also presented at AAD, indicated that a higher proportion of upadacitinib-treated individuals achieved, at the 16-week mark, skin clearance in atopic dermatitis across all of their bodily regions compared to dupilumab.2 As the investigative team now sought to elucidate the mechanisms driving the observed superior response among patients with atopic dermatitis to upadacitinib, they out to assess disease-associated serum biomarkers in the LEVEL-UP trial.1,2

The trial participants who had received upadacitinib, with a 15mg QD starting dose adjusted based on clinical response, or dupilumab, had their biomarkers analyzed by Eyerich and colleagues at the point of baseline through the 16-week mark. The biomarkers that were implicated in disease pathogenesis were assessed via enzyme-linked immunosorbent assays and then reported at the 0, 4, 8, and 16-week marks.

The investigators implemented a mixed-effects model for repeated measures, using the model to calculate percent changes from the point of baseline and to determine their findings’ statistical significance. Overall, the team concluded that upadacitinib robustly affected type 2 inflammation among subjects (CCL26, CCL17, and eosinophil count).1

It impacted inflammation while exhibiting early and continued reductions in participants’ biomarkers that were linked to inflammation (type 22 [IL-22] and type 1 [CXCL10]) and to impaired skin barrier function (beta-defensin 2 [BD2]).1

The investigative team furthe noted that while dupilumab had a notable impact on type 2 markers among LEVEL-UP participants, the effects observed by the team on IL-22 and BD2 were shown to be less pronounced. In fact, they highlighted that there was no impact on CXCL10.

The team also did not note differential impact on CCL17 or CCL26 following dupilumab therapy between participants who attained Week 16 EASI90 or those who did not.1 This, the investigators expressed, suggested that type 2 inflammation impact alone does not predict EASI 90 responses among subjects.

Eyerich and colleagues further highlighted that in patients who required a dose escalation to 30mg of upadacitinib, higher baseline levels and lower reductions in CCL26, CCL17, IL-22, and BD2 during the time of escalation were observed compared to those who remained on upadacitinib 15mg.

After the period in which doses were raised, the investigators noted secondary reductions in participants’ biomarkers. They highlighted that these underpinned a molecular basis that is behind requisite drug escalation as needed to attain optimal clinical responses for those with atopic dermatitis.

Overall, the team’s data suggest impacts on multiple disease nodes as necessary for achievement of high levels of efficacy. Additionally, the mechanistic rationale supports the move to escalate to 30mg of upadacitinib for some individuals to get an EASI 90 response.

For more data presented at AAD, view related studies and recent findings covered at the conference here.

References

1. Eyerich K, Kwatra S, Parmentier J, et al. Impact on Multiple Inflammatory Axes Drives a High Level of Efficacy to Upadacitinib: Biomarker Analysis from LEVEL-UP, a Phase 3b/4 Head-to-Head Study with Dupilumab. Presented at the 2025 American Academy of Dermatology (ADA) Annual Meeting. Orlando, FL. March 07-11, 2025.

2. Eyerich K, Torres T, Silverberg J, et al. Higher Levels of Skin Clearance Across Body Regions with Upadacitinib versus Dupilumab in Patients with Moderate-to-Severe Atopic Dermatitis. Presented at the 2025 American Academy of Dermatology (ADA) Annual Meeting. Orlando, FL. March 07-11, 2025.