Experts Delve Into Upadacitinib vs Dupilumab: Insights From LEVEL UP

In a recent Dermatology Times Between the Lines custom video series, “Level Up: Efficacy and Safety of Upadacitinib vs Dupilumab in Adults and Adolescents With Moderate to Severe Atopic Dermatitis,” experts discussed results of an open-label, efficacy assessor-blinded head-to-head phase 3b/4 study. The LEVEL UP study (NCT05601882) compared upadacitinib (Rinvoq; AbbVie) with dupilumab (Dupixent; Regeneron and Sanofi) in adults and adolescents with moderate to severe atopic dermatitis (AD).¹

Raj Chovatiya, MD, PhD, MSCI, a clinical associate professor at the Rosalind Franklin University Chicago Medical School in Illinois and the founder and director of the Center for Medical Dermatology and Immunology Research, joined Christopher Bunick, MD, PhD, an associate professor of dermatology and translational biomedicine at the Yale University School of Medicine in New Haven, Connecticut, to share pearls and insights from the ongoing study. Bunick is also an investigator involved in the LEVEL UP clinical trial.

LEVEL UP Study

The LEVEL UP study involved patients aged 12 to 64 years who had symptoms of AD for at least 3 years and an Eczema Area and Severity Index (EASI) score of 16 or greater, Investigator Global Assessment score of 3 to 4, and an affected body surface area of 10% or greater. Patients were required to have a history of previous inadequate response to another systemic therapy that did not include the evaluated drugs.²

“These are really pretty significantly, severely involved patients that can teach us a lot about how these medications stack up,” Chovatiya noted.

Dose escalation was built in at week 4 for patients who had not achieved EASI 50 or a 4-point improvement in itch, upon which they would be escalated to 30-mg upadacitinib. At week 8, patients who had not achieved EASI 75 or a 4-point improvement in itch were similarly able to escalate to 30-mg upadacitinib.¹

“We really wanted to know what’s happening in the real world per the label,” Bunick said. “Every 4 weeks, you should be evaluating whether you need to step up in dose.”

Additionally, Bunick and Chovatiya discussed that the study employed a protocol for rescue therapy. Topical therapy was occasionally introduced 4 weeks after escalation for patients treated with upadacitinib. The investigators also examined biomarkers, assessing lesional vs nonlesional skin. To date, only data from period 1 of the study have been released, with period 2 data yet to be shared.

At week 16, upadacitinib demonstrated superiority vs dupilumab at approximately 20% achieving primary end points of EASI 90 and Worst Pruritus Numerical Rating Scale (WP-NRS) 0/1 vs approximately 9%. Of the patients treated with upadacitinib, 40.8% achieved EASI 90, whereas 22.5% to 23% of patients treated with dupilumab achieved the same goal. Furthermore, 30.2% of patients treated with upadacitinib achieved a WP-NRS score of 0/1, whereas 15.5% of patients treated with dupilumab achieved the same score.¹

Measuring Burden vs Success

Bunick shared that dermatology clinicians are increasingly faced with a crucial and growing question: “Can I—and should I—switch my patient’s therapy?”

“First and foremost, what we need to understand is that we have to be able to look at the patient and know when their response isn’t good enough,” Bunick said.

Quality of life issues, such as itch and sleep, often serve as crucial quantifiers for identifying whether a treatment modality is meeting the benchmarks necessary to indicate clinical success. “The standard of care in atopic dermatitis has been shifted tremendously, and there is a new standard that therapies have to reach in order to be considered highly efficacious,” Bunick said.

Chovatiya concurred, emphasizing the multidimensional burden of AD. “There’s no way to really understand what’s going on with the disease itself when you’re quite simply focusing on the rash... a single aspect of the disease,” he said. “It’s only until we start layering our understanding to be multifold, more complex, that I think we’re going to really unlock the potential of all the medications we have available to us.”

Valuing Composite End Points

“One of the most important things about this trial is this composite end point,” Bunick said. “Never before in a clinical trial in atopic dermatitis have we combined EASI 90, really a clinical, provider-driven metric, with a patient-driven metric like itch.”

Bunick compared the AD trial landscape with psoriasis research, sharing that their evolutions are parallel. Benchmarks for clinical success were formerly much lower (eg, Psoriasis Area and Severity Index scoring) and have been increased over time with the addition of patient-driven metrics also being taken into consideration.

“It’s not good enough to have just skin clearance or itch clearance,” he emphasized. “You have to have both the skin clearance and the itch reduction.”

Bunick and Chovatiya discussed the TARGET-DERM registry. In 2023, data were released demonstrating that if a patient with AD had an itch score of 0 or 1, their quality of life was 30% to 40% better than patients with an itch score of 2 or higher.³

“One thing that we really don’t need as much of in psoriasis that we really need more of in atopic dermatitis, aside from elevated end points, is flexibility,” Chovatiya said. “The idea is that you can really tailor the way you treat, both in terms of route of administration and even medication type and dosing, to exactly where the patient is at.”

References

1. New data show Rinvoq (upadacitinib) demonstrated superiority versus Dupixent (dupilumab) across primary and all secondary end points in an open-label head-to-head atopic dermatitis study. News release. AbbVie. April 25, 2024. Accessed September 13, 2024. https://news.abbvie.com/2024-04-25-New-Data-Show-RINVOQ-R-upadacitinib-Demonstrated-Superiority-Versus-DUPIXENT-R-dupilumab-Across-Primary-and-All-Secondary-Endpoints-in-an-Open-Label-Head-to-Head-Atopic-Dermatitis-Study
2. A study to evaluate adverse events and change in disease activity comparing oral upadacitinib to subcutaneous dupilumab in adolescent and adult participants with moderate to severe atopic dermatitis (Level Up). ClinicalTrials.gov. Updated August 21, 2024. Accessed September 16, 2024. https://clinicaltrials.gov/study/NCT05601882
3. Immune-mediated inflammatory skin conditions (DERM). TARGET RWE. Accessed September 13, 2024. https://targetrwe.com/unique-data/registries/target-derm/