383 Integrated safety analysis of abrocitinib in 635 adolescent patients with moderate-to-severe atopic dermatitis with over 1000 patient-years of exposure
Authors: Paller Amy S , Eichenfield Lawrence F , Silverberg Jonathan I , Cork Michael J   , Bangert Christine  , Irvine Alan D , Weidinger Stephan  , Barbarot Sebastien  , Fan Haiyun  , Alderfer Justine , Koppensteiner Herwig  , Chittuluru Kanti 
Published: June 2023

Abstract
Abrocitinib is an oral, once-daily, Janus kinase 1–selective inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD). Recently, the US Food and Drug Administration expanded the indication of abrocitinib in adolescent patients with moderate-to-severe AD aged 12 to &lt;18 years. Abrocitinib was efficacious and well tolerated in adolescent patients exposed for approximately 1 year of treatment in the JADE clinical program. This study aims to describe the updated long-term integrated safety profile of abrocitinib in adolescent patients treated in the JADE clinical program. This interim integrated safety analysis assessed data from patients aged 12 to &lt;18 years who participated in the phase 3 JADE clinical trials MONO-1 (NCT03349060), MONO-2 (NCT03575871), TEEN (NCT03796676) and REGIMEN (NCT03627767) and subsequently enrolled in the ongoing phase 3 extension trial JADE EXTEND (NCT03422822; data cutoff: September 25, 2021). Data were pooled in two cohorts. The consistent-dose cohort comprised patients who received the same abrocitinib dose (200 or 100 mg) during the entire exposure time in the qualifying JADE trials, MONO-1, MONO-2 and TEEN and/or in JADE EXTEND. This cohort also included patients who did not meet the inclusion criteria for the maintenance period of JADE REGIMEN after abrocitinib 200 mg induction in the open-label period and subsequently received abrocitinib 200 mg in JADE EXTEND. The variable-dose cohort included patients who were randomly assigned to the maintenance period of JADE REGIMEN after induction and, hence, received different abrocitinib doses throughout exposure time in JADE REGIMEN, and subsequently entered in JADE EXTEND. Incidence rates (IRs) along with 95% CIs are presented as numbers of patients with events per 100 patient-years (PY). The analysis included 635 adolescent patients (exposure: 1011.4 PY). The consistent-dose cohort comprised 490 adolescents (730.6 PY): 289 received abrocitinib 200 mg (424.5 PY) and 201 received abrocitinib 100 mg (306.1 PY). Duration of exposure was ≥96 weeks in 38% and 37%, and ≥144 weeks in 8% and 4% of patients who received abrocitinib 200 or 100 mg, respectively. In the 200- and 100-mg arms, adverse events (AEs) occurred in 243 (84%) and 153 (76%) patients; 8% (IR [95% CI], 5.87 [3.76–8.74]) and 9% (5.87 [3.48–9.27]) experienced severe AEs and 10% (6.96 [4.69–9.93]) and 8% (5.13 [2.93–8.33]) discontinued the study due to AEs, respectively. The IRs of AEs of special interest were 1.84 (95% CI, 0.79–3.62) and 1.28 (0.35–3.27) for serious infection, 2.11 (0.97–4.01) and 1.62 (0.53–3.77) for all herpes zoster infections, and 0.69 (0.14–2.03) and 0.32 (0.01–1.77) for opportunistic herpes zoster infections in the 200- and 100-mg arms, respectively. One patient (aged 16 years) in the 200-mg arm had a nonfatal venous thromboembolism (VTE) event (pulmonary embolism; IR, 0.23 [95% CI, 0.01–1.28]); patient had a family history of pulmonary embolism. The variable-dose cohort comprised 145 adolescents (exposure: 280.8 PY). Adverse events occurred in 139 patients (96%) exposed to either abrocitinib dose; 10% (IR [95% CI], 5.15 [2.81–8.64]) had severe AEs and 11% (5.66 [3.23–9.19]) discontinued the study due to AEs. The IRs of AEs of special interest were 1.05 (95% CI, 0.22–3.07) for serious infection, 2.17 (0.80–4.72) for all herpes zoster infections and 0.35 (0.01–1.96) for opportunistic herpes zoster infections; no patients had VTE in the variable-dose cohort. In both the consistent-dose and variable-dose cohorts, there were no events of nonmelanoma skin cancer or other malignancies, tuberculosis or other opportunistic infections (excluding herpes zoster), major adverse cardiovascular events or deaths. In this integrated safety analysis using the most recent data cut from the ongoing JADE EXTEND trial, abrocitinib had an acceptable long-term safety profile in adolescents with moderate-to-severe AD.