Efficacy and Safety of Variable-Dose Versus Continuous-Dose Abrocitinib Treatment in Patients with Moderate-to-Severe...

Signs and symptoms of atopic dermatitis (AD) can fluctuate over time, necessitating a flexible dosing treatment approach for long-term management. This study evaluated the long-term efficacy and safety of variable-dose abrocitinib treatment in patients with moderate-to-severe AD compared with continuous abrocitinib 200-mg dosing.

Patients from phase 3 trials in the JADE clinical program were divided into a continuous abrocitinib 200-mg dose cohort or a variable-dose cohort that received abrocitinib 100 mg and 200 mg at different phases of the trial(s).

At week 48 of abrocitinib treatment, 82% and 69% attained 75% improvement from baseline in the Eczema Area and Severity Index in the continuous abrocitinib 200 mg (n = 941) and variable-dose (n = 90) cohorts, respectively, while 67% and 44% achieved a ≥ 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS4) response. In the continuous abrocitinib 200 mg and variable-dose cohorts, respectively, 23% and 13% achieved complete skin clearance per the Investigator's Global Assessment score of 0, and 44% and 21% achieved a PP-NRS of 0/1 (profound itch control). Similar trends were observed for patient-reported outcomes. Incidence rates for serious adverse events-those leading to discontinuation, deaths, and serious infections-were numerically higher in the variable-dose cohort but numerically lower for malignancies (excluding nonmelanoma skin cancer, major adverse cardiovascular events, venous thromboembolism, thrombocytopenia, lymphopenia, and retinal detachment compared with the continuous abrocitinib 200 mg cohort.

Thus, sustained long-term efficacy was observed with both continuous abrocitinib 200 mg and variable-dose abrocitinib, with no new safety signals. Treatment with continuous abrocitinib 200 mg was the more efficacious treatment regimen, but flexible dosing with abrocitinib may be a viable treatment approach depending on individual patient characteristics and needs. Video abstract available for this article.

ClinicalTrials.gov identifiers NCT03349060 (trial registration date: November 17, 2017); NCT03575871 (trial registration date: June 15, 2018); NCT03720470 (trial registration date: October 24, 2018); NCT03796676 (trial registration date: January 4, 2019); NCT03627767 (trial registration date: May 29, 2018); NCT04345367 (trial registration date: March 27, 2020); NCT03422822 (trial registration date: December 20, 2017). Video Abstract (mp4 2239 KB).