Upadacitinib Demonstrates Efficacy in Patients With AD and Head and Neck Involvement

This week at the 33rd European Academy of Dermatology and Venereology (EADV) Congress held in Amsterdam, AbbVie presented new data on the efficacy of upadacitinib (Rinvoq) for the treatment of patients with atopic dermatitis in the head and neck regions. According to the poster authors, atopic dermatitis on the head and neck is often difficult to treat and refractory to existing treatments. Atopic dermatitis on the head and neck can also be associated with increased rates of anxiety and depression in patients due to these areas being more visible than others.¹

Overall, upadacitinib 15mg and upadacitinib 30mg outperformed placebo regarding a greater proportion of patients achieved a clinically meaningful improvement, defined by a decrease in the head and neck EASI score over 16 weeks.¹

To take an in-depth look at the significance of the Measure Up 1 and Measure Up 2 phase 3 studies and their evaluation of upadacitinib, Dermatology Times spoke with Kilian Eyerich, MD, PhD, poster author and chair and professor at the department of dermatology and venerology of the University of Freiburg in Germany.

Q&A With Kilian Eyerich, MD, PhD

Kilian Eyerich, MD, PhD

Image credit: AbbVie

Dermatology Times: Can you provide an overview of the new data presented at EADV on upadacitinib for moderate to severe atopic dermatitis?

Eyerich: New post-hoc analysis of the ongoing phase 3 studies (Measure Up 1 and Measure Up 2) showed that a higher proportion of patients with moderate to severe atopic dermatitis (AD) with varying degrees of head and neck involvement treated with upadacitinib achieved the following optimal treatment targets compared to placebo at week 16:

• Near complete skin clearance in the head and neck region (EASI Head & Neck Score < 1), minimal or no impact on quality of life (DLQI 0/1), and minimal disease activity, which is the simultaneous achievement of near complete skin clearance (EASI 90) and no to little itch (WP-NRS 0/1). Specific data for each endpoint can be found in the press release.

DT: What differentiates upadacitinib from other treatments currently available for AD, especially in high-impact areas such as the head and neck?

Eyerich: Research shows that AD in the head and neck region can have a significant impact on symptom frequency and quality of life for patients, which contributes to the disease burden and is often associated with poorer clinical outcomes. Despite taking steps to manage their condition, patients still continue to suffer from these debilitating symptoms, especially with visible head and neck involvement.

This analysis demonstrates the efficacy of a targeted systemic therapy in varying degrees of severity in the head and neck AD involvement. Upadacitinib also achieves minimal disease activity – the simultaneous achievement of near-complete skin clearance (EASI 90) and no to little itch (WP-NRS 0/1) – and improvements in quality of life measured by DLQI 0/1.

DT: Can you elaborate on the significance of the post-hoc analysis from the ongoing phase 3 studies? How does it enhance our understanding of upadacitinib’s efficacy in head and neck involvement in patients with AD?

Eyerich: These data further underscore the unmet needs contributing to burden among AD patients, despite taking steps to manage their condition. This analysis is the first of its kind to stratify the severity of disease in the head and neck region at baseline, demonstrating the efficacy of upadacitinib (a targeted systemic therapy) in moderate-to-severe AD across all patient subgroups from no-to-mild, moderate, or severe head and neck involvement.

Setting stringent clinical measures is critical in achieving disease control in AD and aiming for a higher standard of care. Positive results from the analysis demonstrate that higher treatment targets are achievable and clinically meaningful results are possible for patients with a targeted systemic therapy, such as upadacitinib.

DT: What impact does the severity of AD in the head and neck region have on patients’ quality of life, and how does upadacitinib help improve these aspects?

Image credit: DermNet

Eyerich: Living with uncontrolled AD can lead to debilitating symptoms that make everyday life difficult. Research shows that AD in the head and neck region can have a significant impact on symptom frequency and quality of life for patients – often experiencing emotional distress and mental health issues, along with physical discomfort in highly visible areas. Plus, these areas have traditionally been challenging to treat with traditional therapies, which can be frustrating.

Results from this new analysis demonstrates that a targeted systemic therapy, such as upadacitinib, can help address these unmet needs with stringent treatment goals to help reach optimized clinical outcomes (near-complete skin clearance, minimal itch, and improvement in quality of life) for patients.

DT: How do the safety and efficacy profiles of upadacitinib and dupilumab compare, particularly in terms of achieving treatment targets like skin clearance and itch resolution?

Eyerich: The head-to-head LEVEL UP study evaluated the efficacy and safety of upadacitinib versus dupilumab in patients with moderate-to-severe AD who had an inadequate response to systemic therapy. In the study results,upadacitinib showed superior efficacy versus dupilumab in the primary endpoint, demonstrating that twice as many patients on upadacitinib had both near-complete skin clearance (EASI 90) and little to no itch (WP-NRS 0/1) in comparison to dupilumab in 16 weeks.

The safety profile of upadacitinib was consistent with the profile in previous atopic dermatitis studies with no new safety signals identified during the 16-week period.

DT: Can you discuss the baseline criteria from the UP-TAINED real-world study? How does this data inform the selection of patients for systemic AD treatment with upadacitinib?

Eyerich: Up-TAINED is a German study looking at how upadacitinib works in adolescents and adults with moderate to severe AD in real-world settings. The study shows that patients treated with upadacitinib actually met all three “must-have” criteria for systemic therapy, including things like objective disease severity, disease burden such as pruritus or sleep disturbance, and having a poor response to local or systemic therapy. In other words, this study proved that a checklist with these three criteria is good to identify patients that would benefit the most from being treated with upadacitinib.

DT: What are the main takeaways from the 6-month interim analysis of the AD-VISE study regarding upadacitinib’s real-world effectiveness in adults and adolescents?

Eyerich: AD-VISE is another ongoing real-world study looking at outcomes with upadacitinib in adults and teenagers with AD over a 2-year period. The EADV poster shows updated results on how well upadacitinib worked after 2, 4, and 6 months of treatment, compared to the start.

Most patients with AD had clear or almost clear skin and less itch after two months of treatment with upadacitinib. These results got better or stayed the same through 6 months. Almost half of the patients (47.3%) had a 90% improvement in their EASI score, which is a score of disease severity, after 2 months, and 60.7% had this improvement after 6 months. Also, 40.5% of patients had a WP-NRS score of 0 or 1 after 2 months, and this was similar at 6 months (42.3%). Other signs of minimal disease activity were also generally the same through 6 months. The study results were similar to those from AD clinical trials, showing that dermatologists can expect to see the same results in their everyday practice. Since there is limited real-world data for upadacitinib in AD, this study helps fill that gap.

Reference

1. Eyerich K, Mendes-Bastos P, Holzer G, et al. Efficacy of upadacitinib in treating atopic dermatitis in the head and neck regions. Poster presented at: 33rd European Academy of Dermatology and Venereology Congress; September 25-28, 2024; Amsterdam.