Abrocitinib versus Placebo or Dupilumab for Atopic Dermatitis.

Abstract

BACKGROUND:

The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited.

METHODS:

In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16.

RESULTS:

A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P<0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P<0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Nausea occurred in 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group, and acne occurred in 6.6% and 2.9%, respectively.

CONCLUSIONS:

In this trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.).

• Authors: Thomas Bieber, Eric L Simpson, Jonathan I Silverberg, Diamant Thaçi, Carle Paul, Andrew E Pink, Yoko Kataoka, Chia-Yu Chu, Marco DiBonaventura, Ricardo Rojo, Jeremias Antinew, Ileana Ionita, Rodney Sinclair, Seth Forman, Jacek Zdybski, Pinaki Biswas, Bimal Malhotra, Fan Zhang, Hernan Valdez, JADE COMPARE Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 384 Issue 12 Pg. 1101-1112 (03 25 2021) ISSN: 1533-4406 [Electronic] United States
• PMID: 33761207 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Massachusetts Medical Society.

Chemical References

• Antibodies, Monoclonal, Humanized
• Immunoglobulin A
• Interleukin-4 Receptor alpha Subunit
• Placebos
• Protein Kinase Inhibitors
• Pyrimidines
• Sulfonamides
• dupilumab
• abrocitinib
• Janus Kinase 1

Topics

• Administration, Oral
• Adult
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Dermatitis, Atopic (drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Immunoglobulin A (blood)
• Injections, Subcutaneous
• Interleukin-4 Receptor alpha Subunit (antagonists & inhibitors)
• Janus Kinase 1 (antagonists & inhibitors)
• Male
• Placebos (therapeutic use)
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Pruritus (drug therapy)
• Pyrimidines (administration & dosage, adverse effects)
• Severity of Illness Index
• Sulfonamides (administration & dosage, adverse effects)