Once-daily abrocitinib for up to 16 weeks significantly reduced the signs and symptoms of moderate to severe atopic dermatitis (AD) better than placebo, and abrocitinib was also better than dupilumab for reducing itch response by 2 weeks, according to study findings published in the New England Journal of Medicine.
The findings were part of the phase 3 JADE COMPARE trial. Participants in this trial had AD unresponsive to topical therapy or had disease that warranted systemic therapy. The JADE COMPARE investigators randomly assigned patients to once daily, orally delivered 200 mg (n=226) or 100 mg (n=238) abrocitinib, subcutaneous 300 mg dupilumab every other week (n=243), or placebo (n=131). In addition to their assigned therapy, patients in each group also received topical therapy.
The investigators compared groups in respect to a 2-point or more improvement on the Investigator’s Global Assessment (IGA) response from baseline to week 12. In addition, the researchers looked for an Eczema Area and Severity Index–75 (EASI-75) response, defined by a 75% or greater improvement in the EASI score from baseline to week 12.
Additional secondary endpoints included the week 2 itch response, defined as a 4-point or more improvement in the Peak Pruritus Numerical Rating Scale score, as well as the 16-week IGA and EASI-75 responses.
A significantly higher percentage of patients in the 200-mg abrocitinib group had an IGA response at week 12 compared with those in the placebo group (48.4% vs 14.0%, respectively). Approximately 36.6% in the 100-mg abrocitinib group and 36.5% in the dupilumab arm had an IGA response at the 12-week follow-up.
The weighted difference in the percentage of study participants who had an IGA response at this time point between the 200-mg abrocitinib arm and the placebo arm was 34.8 percentage points (95%, CI, 26.1-43.5; P<.001), and the weighted difference between the 100-mg abrocitinib arm and the placebo group was 23.1 percentage points (95% CI, 14.7-31.4; P <.001).
At 12 weeks, an EASI-75 response was found in 70.3% of patients in the 200-mg abrocitinib group, 58.7% of patients in the 100-mg abrocitinib arm, 58.1% of patients in the dupilumab group, and 27.1% of patients in the placebo group.
In an analysis comparing the 200-mg abrocitinib group and the placebo group, the investigators reported a 43.2 percentage-point (95% CI, 33.7-52.7) weighted difference in the percentage of patients who had an EASI-75 response at week 12. In addition, the weighted difference between the 100-mg abrocitinib group and the placebo arm was 31.9 percentage points (95% CI, 22.2-41.6) (P <.001).
Treatment with the 200-mg dose of abrocitinib was superior to dupilumab in regard to the 2-week itch response (95% CI, 13.5-30.7; P=P <.001).
A higher rate of nausea was recorded in the 200-mg abrocitinib group (11.1%) relative to the 100-mg abrocitinib dose (4.2%). Acne occurred in 6.6% and 2.9% of participants taking the 200- and 100-mg doses of abrocitinib, respectively.
A limitation of the study was its relatively short duration, at least in comparison to AD which is a lifelong disease. Investigators suggest additional follow-up is needed to determine the longer-term efficacy and safety of abrocitinib vs dupilumab and placebo.
The investigators added that “longer and larger trials are necessary to determine the efficacy and safety of abrocitinib and to compare it with other JAK inhibitors and with biologic agents used for the treatment of atopic dermatitis.”
Disclosure: This clinical trial was supported by Pfizer. Please see the original reference for a full list of authors’ disclosures.
Bieber T, Simpson EL, Silverberg JI, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384(12):1101-1112. doi:10.1056/NEJMoa2019380