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Abrocitinib, a once-daily Janus kinase (JAK) 1 selective inhibitor, succeeded as a treatment for moderate-to-severe atopic dermatitis, according to the phase III JADE MONO-2 trial.

In the 12-week double-blind study of 391 individuals, a significantly greater proportion of patients on either 200 or 100 mg of abrocitinib achieved the co-primary endpoint of an Investigator Global Assessment (IGA) response -- defined as a score of clear or almost clear with an improvement of 2+ grades from baseline -- versus placebo (38.1%, 28.4%, and 9.1%, respectively, P<0.001), reported Jonathan Silverberg, MD, PhD, of the George Washington University School of Medicine and Health Sciences in Washington, D.C., and colleagues.

As shown in the study online in , more people on 200 or 100 mg of abrocitinib monotherapy also achieved the other co-primary endpoint of having at least a 75% improvement in Eczema Area and Severity Index (EASI-75) score compared with placebo after 12 weeks (61%, 44.5%, and 10.4%, respectively, P<0.001).

"Similar to the , IGA and EASI-75 responses were observed as early as week 2 of treatment and were sustained until week 12," the researchers wrote. "Furthermore, similar IGA and EASI-75 responses were observed in analyses for patients younger than 18 years or 18 years or older."

Current available treatment options for moderate-to-severe atopic dermatitis include corticosteroids, calcineurin inhibitors, tars, antibiotic creams, and topical antihistamines. Additionally, the subcutaneous biologic dupilumab (Dupixent), an interleukin-4 receptor monoclonal antibody, was first approved for moderate-to-severe atopic dermatitis in March 2017, with a recent label expansion in May 2020 to carry an indication for use in children as young as age 6.

Multiple JAK inhibitors are now approved for rheumatoid arthritis; one is also approved for psoriatic arthritis, and trials are underway with these agents for psoriasis. It's reasonable, therefore, to think they could also help in atopic dermatitis.

Participants in the study by Silverberg and co-authors were enrolled from 115 medical centers worldwide, and included 155 patients who received 200 mg a day of abrocitinib, 158 who received 100 mg a day, and 78 who received placebo.

The cohort included patients age 12 and older with a diagnosis of moderate-to-severe atopic dermatitis for a minimum of 1 year, who had an "inadequate response" to topical treatments for at least 1-6 months.

The trial also achieved key secondary endpoints, including a greater proportion of patients achieving at least a four-point improvement in itching, measuring on the Peak Pruritus Numerical Rating Scale (P<0.001):

• 200-mg abrocitinib: 55.3% (95% CI 47.2-63.5%)

• 100-mg abrocitinib: 45.2% (95% CI 37.1-53.3%)

• Placebo: 11.5% (95% CI 4.1-19.0%)

Additionally, there was a greater proportion of patients on abrocitinib who had at least 90% improvement in the Eczema Area and Severity Index score (37.7% on 200 mg; 23.9% on 100 mg; and 3.9% on placebo).

The researchers reported that the treatment was considered relatively safe, with only 1.3% of those on the 200 mg dose experiencing any serious adverse events, compared with 3.2% of those on 100 mg of abrocitinib and 1.3% of those on placebo. However, 1.3% and 3.2% of those on the 200 mg dose had decreases in platelet count and thrombocytopenia, respectively.

"Future studies and analyses should focus on the long-term efficacy and safety of abrocitinib in patients with moderate-to-severe [atopic dermatitis] and in adolescents and nonwhite patients, and explore the use of abrocitinib in combination with topical therapies," the researchers concluded.

Pfizer has announced plans to of abrocitinib later this year. The drug was granted FDA Breakthrough Therapy designation in February 2018, and if approved, will be the first once-daily oral treatment option for moderate to severe atopic dermatitis.

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