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. 2021 Sep;22(5):693-707. doi: 10.1007/s40257-021-00618-3. Epub 2021 Aug 18.

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.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • 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
  • Protein Kinase Inhibitors / adverse effects*
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects*
  • Risk Factors
  • Skin Neoplasms / epidemiology*
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects*
  • Time Factors
  • Venous Thromboembolism / epidemiology
  • Young Adult

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • abrocitinib

Associated data

  • ClinicalTrials.gov/NCT03422822
  • ClinicalTrials.gov/NCT03349060
  • ClinicalTrials.gov/NCT03627767
  • ClinicalTrials.gov/NCT03575871
  • ClinicalTrials.gov/NCT03720470
  • ClinicalTrials.gov/NCT02780167