Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial.

BACKGROUND: The heterogeneous course of moderate-to-severe atopic dermatitis necessitates treatment flexibility. OBJECTIVE: We evaluated the maintenance of abrocitinib-induced response with continuous abrocitinib treatment, dose reduction or withdrawal, and response to treatment reintroduction following flare (JAK1 Atopic Dermatitis Efficacy and Safety [JADE] REGIMEN: National Clinical Trial 03627767). METHODS: Patients with moderate-to-severe atopic dermatitis responding to open-label abrocitinib 200 mg monotherapy for 12 weeks were randomly assigned in a 1:1:1 ratio to blinded abrocitinib (200 or 100 mg) or placebo for 40 weeks. Patients experiencing flare received rescue treatment (abrocitinib 200 mg plus topical therapy). RESULTS: Of 1233 patients, 798 responders to induction (64.7%) were randomly assigned. The flare probability during maintenance was 18.9%, 42.6%, and 80.9% with abrocitinib 200 mg, abrocitinib 100 mg, and placebo, respectively. Among patients with flare in the abrocitinib 200 mg, abrocitinib 100 mg, and placebo groups, 36.6%, 58.8%, and 81.6% regained investigator global assessment 0/1 response, respectively, and 55.0%, 74.5%, and 91.8% regained eczema area and severity index response, respectively, with rescue treatment. During maintenance, 63.2% and 54.0% of patients receiving abrocitinib 200 and 100 mg, respectively, experienced adverse events. LIMITATIONS: The definition of protocol-defined flare was not established, limiting the generalizability of findings. CONCLUSION: Induction treatment with abrocitinib was effective; most responders continuing abrocitinib did not flare. Rescue treatment with abrocitinib plus topical therapy effectively recaptured response.

Efficacy and safety of abrocitinib monotherapy in adolescents and adults: a post hoc analysis of the phase 3 JAK1 atopic dermatitis efficacy and safety (JADE) REGIMEN clinical trial.

BACKGROUND: Differences in atopic dermatitis (AD) disease course and manifestation with age may extend to treatment response. OBJECTIVE: To evaluate response maintenance with continuous-/reduced-dose abrocitinib or withdrawal and response to treatment reintroduction after flare in adolescent and adult participants in JADE REGIMEN (NCT03627767). METHODS: Adolescents (12-17 years) and adults with moderate-to-severe AD responding to abrocitinib 200-mg induction were randomly assigned to 40-week maintenance with abrocitinib (200 mg/100 mg) or placebo. Patients who experienced flare during maintenance received rescue treatment. RESULTS: Of 246 adolescents and 981 adults, 145/246 (58.9%) and 655/981 (66.8%), respectively, responded to induction. Similar proportions of adolescents and adults experienced flare during maintenance with abrocitinib 200 mg (14.9%/16.9%), 100 mg (42.9%/38.9%), and placebo (75.5%/78.0%). From the abrocitinib 200-mg, 100-mg, and placebo arms, respectively, Eczema Area and Severity Index response was recaptured by 28.6%, 25.0%, and 52.9% of adolescents and 34.3%, 33.7%, and 58.0% of adults; Investigator's Global Assessment response, by 42.9%, 50.0%, and 73.5% of adolescents and 34.3%, 50.6%, and 74.1% of adults. Abrocitinib had a similar safety profile regardless of age; nausea incidence was higher in adolescents. LIMITATIONS: Adolescents represented 20% of the trial population. CONCLUSION: Abrocitinib was effective in preventing flare in adolescents and adults.Clinicaltrials.gov listing: NCT03627767.