Back to Search
Start Over
Abrocitinib versus Placebo or Dupilumab for Atopic Dermatitis
- Source :
- The New England journal of medicine. 384(12)
- Publication Year :
- 2021
-
Abstract
- 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.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.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 (P0.001 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 (P0.001 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.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.).
- Subjects :
- Adult
Male
medicine.medical_specialty
Injections, Subcutaneous
Administration, Oral
030204 cardiovascular system & hematology
Placebo
Antibodies, Monoclonal, Humanized
Severity of Illness Index
law.invention
Dermatitis, Atopic
Placebos
03 medical and health sciences
0302 clinical medicine
Randomized controlled trial
Double-Blind Method
law
Severity of illness
medicine
Humans
030212 general & internal medicine
Protein Kinase Inhibitors
Sulfonamides
Janus kinase 1
Dose-Response Relationship, Drug
business.industry
Pruritus
Interleukin-4 Receptor alpha Subunit
General Medicine
Atopic dermatitis
Janus Kinase 1
medicine.disease
Dermatology
Dupilumab
Immunoglobulin A
body regions
Clinical trial
Pyrimidines
Monoclonal
Female
business
Subjects
Details
- ISSN :
- 15334406 and 03720470
- Volume :
- 384
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- The New England journal of medicine
- Accession number :
- edsair.doi.dedup.....4390700af81f09845cfe132c7ce25d8a