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

Eric L Simpson, Jonathan I Silverberg, Audrey Nosbaum, Kevin L Winthrop, Emma Guttman-Yassky, Karin M Hoffmeister, Alexander Egeberg, Hernan Valdez, Min Zhang, Saleem A Farooqui, William Romero, Andrew J Thorpe, Ricardo Rojo, Susan Johnson


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: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.

Original languageEnglish
JournalAmerican Journal of Clinical Dermatology
Issue number5
Pages (from-to)693-707
Number of pages15
Publication statusPublished - Sep 2021


  • Acne Vulgaris/chemically induced
  • Adolescent
  • Adult
  • Aged
  • Cardiovascular Diseases/epidemiology
  • Cholesterol, HDL/blood
  • Cholesterol, LDL/blood
  • Dermatitis, Atopic/drug therapy
  • Female
  • Headache/chemically induced
  • Herpes Simplex/epidemiology
  • Herpes Zoster/epidemiology
  • Humans
  • Incidence
  • Infections/epidemiology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Nausea/chemically induced
  • Platelet Count
  • Protein Kinase Inhibitors/administration & dosage
  • Pyrimidines/administration & dosage
  • Risk Factors
  • Skin Neoplasms/epidemiology
  • Sulfonamides/administration & dosage
  • Time Factors
  • Venous Thromboembolism/epidemiology
  • Young Adult


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