Integrated Safety Analysis of Abrocitinib in 3850 Patients With Moderate-To-Severe Atopic Dermatitis: Data From More Than 9600 Patient-Years With Up to 6.5 Years of Exposure

Abstract

Introduction: Atopic dermatitis (AD) is a chronic, inflammatory skin disease that may require long-term disease management. The oral, once-daily Janus kinase 1–selective inhibitor abrocitinib has demonstrated efficacy through 112 weeks in patients with moderate-to-severe AD. Previous integrated safety analyses assessed adverse events of special interest (AESIs) by age and smoking status in 3802 patients (>5200 patient years [PY]; 4 years of abrocitinib exposure) and by age and cardiovascular (CV) risk factors in 3848 patients (>7000 PY; 4.5 years exposure). This study evaluated safety events stratified by age and smoking status using data from patients with ≥6.5 years of abrocitinib exposure.

Procedure/study: Analysis included patients from 8 clinical trials (phase 2b [NCT02780167], JADE MONO-1 [NCT03349060], MONO-2 [NCT03575871], REGIMEN [NCT03627767], COMPARE [NCT03720470], TEEN [NCT03796676], MOA [NCT03915496], and DARE [NCT04345367]) and 1 long-term extension trial (JADE EXTEND [NCT03422822]; data cutoff: Dec 31, 2024). Incidence rates (IRs; number of patients with events/100 PY) of AESIs were assessed by age (<18; 18 to <40; 40 to <50; 50 to <65; and ≥65 years) and smoking status (never; current/former smoker).  

Results: Of 3850 patients in the pooled safety population (9655.4 PY exposure), 3052 received the same abrocitinib dose (consistent-dose cohort) and 798 patients comprised the variable-dose cohort. IRs in the consistent-dose cohort were numerically higher in older vs younger patients for major adverse CV events (MACEs; <18 years: 0.07 [0.00-0.42]; 18 to <40 y: 0.14 [0.04-0.32]; 40 to <50 y: 0.09 [0.00-0.51]; 50 to <65 y: 0.79 [0.32-1.63]; and ≥65 y: 2.03 [0.74-4.41]) and death (<18 years: 0.00 [95% CI, 0.00-0.28]; 18 to <40 y: 0.05 [0.01-0.20]; 40 to <50 y: 0.09 [0.00-0.51]; 50 to <65 y: 0.34 [0.07-0.99]; and ≥65 years 2.02 [0.74-4.40]). Similar trends were observed for other AESIs, including serious infections, herpes zoster, malignancies (excluding nonmelanoma skin cancer [NMSC]), NMSC, and venous thromboembolism (VTE). IRs for serious infections, malignancies (excluding NMSC), NMSC, MACE, VTE, and death were numerically higher in current/former smokers vs never smokers; herpes zoster IRs were comparable between smoking groups. Data from the variable-dose cohort generally showed similar trends.

Conclusion: These long-term follow-up abrocitinib safety data in patients with >9600 PY of exposure are consistent with previously reported risk profiles. IRs tended to be higher in older patients and current/former smokers.

Funding/Disclosures: This study was funded by Pfizer.