In Atopic Dermatitis Trial, Abrocitinib Offers Faster Itch Relief Than Dupilumab 

Ted Bosworth

October 05, 2021

In patients with moderate to severe atopic dermatitis (AD), abrocitinib, an oral JAK inhibitor, relieved itch more quickly than the monoclonal antibody dupilumab (Dupixent), in a multicenter randomized trial presented as a late breaker at the annual meeting of the European Academy of Dermatology and Venereology.

The earlier onset of action with the JAK inhibitor was achieved even though most patients in both arms were on topical corticosteroids, a design element that "is clinically relevant" for a practical comparison of these two agents, according to Kristian Reich, MD, PhD, Center for Translational Research in Inflammatory Skin Diseases, University Medical Center, Hamburg-Eppendorf, Germany.    

The goal of this phase 3b trial, called JADE DARE, was to compare relative safety and efficacy of these strategies over the early course of treatment, he said.

Over 700 Patients Randomized

JADE DARE enrolled 727 patients over age 18 years who previously had an inadequate response to conventional topical therapies. All had moderate to severe AD defined by criteria such as body surface area ≥10% and Eczema Area Severity Index (EASI) ≥16. They were randomly assigned to 200 mg oral abrocitinib once daily or 300 mg subcutaneous dupilumab (after a loading dose of 600 mg) every 2 weeks. A double-dummy design preserved blinding.

The co-primary endpoints were at least a 4-point improvement in pruritus as measured with the Peak Pruritus Numerical Rating Scale (PP-NRS) score at week 2 and at least a 90% improvement in the EASI (EASI 90) at week 4.

The primary endpoint for pruritus at 2 weeks was reached by nearly twice as many patients randomly assigned to abrocitinib (46.2% vs 25.5%; P < .001). The proportion of those meeting the EASI 90 endpoint at week 4 was also superior on abrocitinib (28.5% vs 14.6%; P < .001)

Advantage for Pruritus Control Dissipates

For the pruritus endpoint, the advantage of abrocitinib slowly diminished over time after the peak difference observed at 2 weeks. Although the advantage at week 4 (58.1% vs 40.8%) and week 8 (65.8% vs 52.7%) remained sizeable, there were very small differences thereafter. However, Reich pointed out that the percentages continued to favor abrocitinib at least numerically through the 26 weeks of follow-up completed so far.

The pattern of response on EASI 90 was not the same. After demonstrating superiority at the 4-week timepoint, the advantage of abrocitinib persisted. When compared at week 16, which was a secondary endpoint of the JADE DARE trial, the advantage of abrocitinib remained significant (54.3% vs 41.9%; P < .001). The advantage of abrocitinib narrowed but remained numerically superior at 26 weeks (54.6% vs 47.6%).

Based on the data collected to date, "abrocitinib is clearly superior early on," Reich said. Moreover, he reiterated that topical corticosteroids were allowed as background therapy in both arms.

"It is difficult to show an advantage for one active therapy over the other in patients on background corticosteroids," Reich maintained.

Both Drugs Are Well Tolerated

The drugs were similarly well tolerated. Serious adverse events were uncommon in either arm. The rate of study dropouts due to an adverse event potentially related to treatment assignment was 3% in each group.

Nausea (19% vs 2%), acne (13.5% vs 2%), and headache (13% vs 7.5%) were all more common in patients randomly assigned to abrocitinib. Conjunctivitis was more common in the group randomly assigned to dupilumab (10% vs 2%).

The two deaths that occurred during this study were in the abrocitinib arm, but one was the result of COVID-19 infection and the other was a cardiovascular event in a patient with risk factors. Neither was considered to be treatment-related.

Abrocitinib's relative selectivity for the JAK1 inhibitor is a potential differentiator from other currently available JAK inhibitors, although direct comparisons of these therapies for clinical activity in AD as well as most other diseases remains limited.

The relatively rapid relief of pruritus with the JAK inhibitor relative to the monoclonal antibody in the JADE DARE trial is likely to be perceived as clinically significant by patients with AD, according to Sonja Ständer, MD, professor of dermatology and neurodermatology at the University Hospital Münster, Germany.

"One of the highest needs of patients with atopic dermatitis is a rapid and profound relief of itch," Ständer, who wrote a review article on AD earlier this year, said in an interview.

Although several current therapies are effective against pruritus, Ständer believes that the higher proportion of patients achieving itch control at 2 weeks on abrocitinib "will attract the attention of affected patients."

However, she added that patients need to take both benefits and risks into account, indicating that clinical utility cannot be judged on a single outcome. In selecting one drug over the others, she advised "a balanced use of therapies."

Abrocitinib was first approved in the United Kingdom in early September, followed by Japan last Thursday, for the treatment of moderate to severe AD in patients ages 12 and older. It is under review elsewhere, including in the United States and the European Union for AD.  

In September, the FDA approved the first JAK inhibitor for treating AD — a topical JAK inhibitor, ruxolitinib.

Reich reports financial relationships with 20 pharmaceutical companies, including Pfizer, which provided funding for the JADE DARE trial. Ständer reports financial relationships with Beiersdorf AG, Galderma, Kliniska, Lilly, Pfizer, and Sanofi.

European Academy of Dermatology and Venereology: Abstract 2933. Presented October 2, 2021.

Ted Bosworth is a medical journalist based in New York City.

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