Abrocitinib was more effective than dupilumab at reducing pruritus and clearing lesions from atopic dermatitis, and demonstrated an acceptable safety profile as well, according to data from a multicenter, randomized, double-blind, active-controlled, parallel-treatment, phase 3 trial published in the Lancet.
Investigators enrolled adult patients with moderate to severe atopic dermatitis who were receiving background medicated topical therapy in the JADE DARE trial. Patients were randomly assigned 1:1 to receive either abrocitinib 200 mg orally daily or dupilumab-matching placebo 300 mg via subcutaneous injection every 2 weeks. The trial lasted for 26 weeks. The primary endpoints were Peak Pruritus Numerical Rating Scale (PP-NRS4) response at week 2 and Eczema Area Severity Index 90% improvement (EASI-90) at week 4. The key secondary endpoint was achieving EASI-90 by week 16. Safety endpoints–including the incidence of adverse events, serious adverse events, those leading to discontinuation–were assessed as well.
There were 727 patients enrolled in the study: 362 in the abrocitinib group and 365 in the dupilumab group. The mean age in both groups was about 35 years, more than half of patients in both groups were men, and the majority of patients in both groups were White.
The percentage of patients reaching PP-NRS4 at week 2 was higher in the abrocitinib group compared with the dupilumab group (48% vs 26%) with a difference of 22.6% (95% CI, 15.8%-29.5%; P <.0001). The percentage of patients who reached EASI-90 at week 4 was also higher in the abrocitinib group compared to the dupilumab group (29% vs 15%) with a between-group difference of 14.1% (95% CI, 8.2%-20.0%; P <.0001). Significantly more patients in the abrocitinib group reached EASI-90 compared with the dupilumab group (54% vs 42%; P =.0008). A secondary analysis showed that patients in the abrocitinib group who achieved EASI-90 at 2 consecutive visits were able to stop medicated topical therapy for a mean of 51 (95% CI, 46-57) days compared with 33 (95% CI, 28-39) days in the dupilumab group.
In the safety analysis, conducted during the 26-week trial period and for 28 days post-therapy, more patients in the abrocitinib group had adverse events compared with the dupilumab group (74% vs 65%). The percentage of patients with adverse events that were serious, severe, or led to study discontinuation were similar between groups. Serious adverse events in the abrocitinib group were considered unrelated to study treatment. A serious adverse event in the dupilumab group, rhabdomyolysis, was possibly related to treatment. Nausea was the most common adverse event in the abrocitinib group, followed by headache, acne or folliculitis, and conjunctivitis. Similar adverse events were observed in the dupilumab group.
The study was limited by its inability to capture rare or long-term adverse events due to its small sample size and short duration.
“Serious adverse events observed in the dupilumab group that were considered related to study treatment,”–namely, rhabdomyolysis–“are not listed in the current prescribing information and must be confirmed in long-term studies or real-world safety assessments,” the study authors wrote.
Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Reich K, Thyssen JP, Blauvelt A, et al. Efficacy and safety of abrocitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: a randomised, double-blind, multicentre phase 3 trial. Lancet. 2022;400(10348):273-282. doi:10.1016/S0140-6736(22)01199-0