Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program

Abstract

Background: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy.

Objective: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study.

Methods: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported.

Results: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 10³/mm³ at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19.

Conclusion: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD.

Trial registries: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.

Fig. 1

Schematic of a placebo-controlled cohort and b all-abrocitinib cohort

Fig. 2

Clinical safety data from baseline to week 16 for a platelets, b absolute lymphocyte count, c absolute neutrophil count, and d hemoglobin. IQR interquartile range, Q quarter. Boxes span the IQR; stars represent the median value; whiskers delineate the maximum and minimum values (maximum = Q3 + 1.5 × IQR; minimum = Q1 − 1.5 × IQR); circles represent outliers

Fig. 2

Clinical safety data from baseline to week 16 for a platelets, b absolute lymphocyte count, c absolute neutrophil count, and d hemoglobin. IQR interquartile range, Q quarter. Boxes span the IQR; stars represent the median value; whiskers delineate the maximum and minimum values (maximum = Q3 + 1.5 × IQR; minimum = Q1 − 1.5 × IQR); circles represent outliers

Fig. 3

Mean percent change from baseline in a LDL-C and b LDL/HDL ratio by visit in the placebo-controlled cohort. CI confidence interval, HDL high-density lipoprotein, LDL low-density lipoprotein, LDL-C low-density lipoprotein cholesterol. Error bars represent standard error

Fig. 4

Line plot of median (Q1, Q3) creatinine kinase (U/L) data by visit in the placebo-controlled cohort. Q quarter. Error bars represent interquartile range