Integrated Efficacy and Safety Analysis of Abrocitinib in Adolescents With Moderate-to-Severe Atopic Dermatitis

Abstract

Background: Abrocitinib has demonstrated long-term efficacy (48 weeks) and safety (~4 years) in adults and adolescents with moderate-to-severe atopic dermatitis (AD). This analysis evaluated abrocitinib efficacy in adolescents through 112 weeks, and safety of up to 4.6 years of exposure.

Methods: Data were from adolescents in JADE MONO-1 (NCT03349060), MONO-2 (NCT03575871), TEEN (NCT03796676), REGIMEN (NCT03627767; safety analysis only), and the ongoing phase 3 extension trial, EXTEND (NCT03422822; data cutoff: September 5, 2022). Efficacy assessments included proportions of patients achieving an Investigator's Global Assessment score of 0 or 1 (IGA 0/1) and ≥ 75%/≥ 90% improvement in Eczema Area and Severity Index (EASI-75/-90). Treatment-emergent adverse events (TEAEs) and AEs of special interest were reported as incidence rate/100 patient-years. A substudy of JADE TEEN assessed immune response to vaccination.

Results: Efficacy was assessed in 170 and 187 patients in the abrocitinib 200-mg and 100-mg arms, respectively; median exposure was 971.0 and 899.0 days. At Week 112, comparable proportions of patients treated with abrocitinib (200, 100 mg) achieved EASI-75 (85%, 83%), EASI-90 (62%, 60%), and IGA 0/1 (57%, 57%). Safety was assessed in 289 and 201 patients in the abrocitinib 200- and 100-mg arms, respectively; median exposure was 882.0 and 863.0 days. Incidence rates were numerically higher with abrocitinib 200 mg versus 100 mg, with overlapping confidence intervals for serious TEAEs (IR [95% CI]; 5.47 [3.69-7.80] vs. 3.45 [1.89-5.80]) and TEAEs leading to discontinuation (6.78 [4.80-9.31] vs. 5.39 [3.38-8.16]).

Conclusions: Efficacy and safety results support long-term abrocitinib use in adolescent patients.

Trail registration: ClinicalTrials.gov Identifiers NCT03349060, NCT03575871, NCT03796676, NCT03627767, NCT03422822.

Keywords: adolescents; atopic dermatitis; efficacy; safety; vaccination.

FIGURE 1

Schematic of efficacy and safety patient cohorts. ^†Patients received concomitant topical medicated therapy (topical corticosteroids, calcineurin inhibitors, and/or crisaborole); patients who received medicated or nonmedicated topical treatments in parent studies were permitted to use these throughout the study. ^‡Patients who did not achieve an IGA score of 0 (clear) or 1 (almost clear) with a ≥ 2‐grade improvement from baseline and ≥ 75% improvement from baseline in EASI after 12 weeks of treatment with abrocitinib 200 mg. ^§Patients may have received their first dose of abrocitinib (100 mg/200 mg) in JADE EXTEND after receiving placebo in a phase 3 placebo‐controlled trial. ^¶Patients in the open‐label run‐in phase who were considered responders (IGA score of 0 [clear] or 1 [almost clear] with a ≥ 2‐grade improvement from baseline and ≥ 75% improvement from baseline in EASI) after 12 weeks of treatment with abrocitinib 200 mg were randomly assigned to treatment with abrocitinib 200 mg, abrocitinib 100 mg, or placebo. ^††Patients who experienced a flare (≥ 50% loss of Week 12 EASI response and new IGA score ≥ 2) during the maintenance period of JADE REGIMEN entered a 12‐week open‐label rescue period. EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment.

FIGURE 2

Proportion of patients who achieved (A) EASI‐75, (B) IGA 0/1^†, (C) EASI‐90, and (D) EASI‐100 responses. As‐observed data are without any imputation for missing values. Using the LOCF method, missing data were imputed as the last observed value. ^†IGA 0/1 response is defined as an IGA score of 0 (clear) or 1 (almost clear) with a ≥ 2‐point improvement from baseline. EASI, Eczema Area and Severity Index; EASI‐75, ≥ 75% improvement from baseline in EASI; EASI‐90, ≥ 90% improvement from baseline in EASI; EASI‐100, 100% improvement from baseline in EASI; IGA, Investigator's Global Assessment; LOCF, last observation carried forward; OD, observed data.

FIGURE 3

Proportion of patients who achieved PP‐NRS4 response. As‐observed data are without any imputation for missing values. Using the LOCF method, missing data were imputed as the last observed value. LOCF, last observation carried forward; OD, observed data; PP‐NRS, Peak Pruritus Numerical Rating Scale; PP‐NRS4, ≥ 4‐point improvement from baseline in PP‐NRS.

FIGURE 4

IRs for (A) serious TEAEs, severe TEAEs, TEAEs leading to study discontinuation, and (B) TEAEs of special interest in the consistent‐dose cohort. ^†Serious infections included: bacterial arthritis, Clostridium difficile infection, COVID‐19, COVID‐19 pneumonia, eczema herpeticum, infectious mononucleosis, muscle abscess, osteomyelitis, peritonsillitis, pharyngitis, pneumonia, pulmonary tuberculosis, skin infection, staphylococcal sepsis, tuberculous pleurisy, and upper respiratory tract infection. HZ, herpes zoster, IR, incidence rate; MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; PY, patient‐years; TEAE, treatment‐emergent adverse event; VTE, venous thromboembolism.

FIGURE 5

Geometric mean fold increase from baseline in IgG against specific Tdap vaccine antigens at 4 weeks post‐vaccination. Statistical significance for the differences between treatment arms was not assessed.