Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program.
Am J Clin Dermatol
; 22(5): 693-707, 2021 Sep.
Article
in En
| MEDLINE
| ID: mdl-34406619
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrimidines
/
Skin Neoplasms
/
Sulfonamides
/
Protein Kinase Inhibitors
/
Dermatitis, Atopic
/
Infections
Type of study:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Prognostic_studies
Limits:
Adolescent
/
Adult
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Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Am J Clin Dermatol
Journal subject:
DERMATOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
United States