Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results

TY - JOUR

T1 - Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results

AU - Silverberg, Jonathan I

AU - de Bruin-Weller, Marjolein

AU - Bieber, Thomas

AU - Soong, Weily

AU - Kabashima, Kenji

AU - Costanzo, Antonio

AU - Rosmarin, David

AU - Lynde, Charles

AU - Liu, John

AU - Gamelli, Amy

AU - Zeng, Jiewei

AU - Ladizinski, Barry

AU - Chu, Alvina D

AU - Reich, Kristian

N1 - Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2022/3

Y1 - 2022/3

N2 - BACKGROUND: Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis.OBJECTIVE: We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks.METHODS: Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] ≥3, and Worst Pruritus Numerical Rating Scale [WP-NRS] score ≥4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg + TCS, or placebo (PBO) + TCS (rerandomized at week 16 to upadacitinib + TCS). Safety and efficacy, including proportion of patients experiencing ≥75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement ≥2 grades (vIGA-AD 0/1), and WP-NRS improvement ≥4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19).RESULTS: Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement ≥4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (≤0.2/100 patient-years).CONCLUSIONS: Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD.

AB - BACKGROUND: Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis.OBJECTIVE: We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks.METHODS: Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] ≥3, and Worst Pruritus Numerical Rating Scale [WP-NRS] score ≥4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg + TCS, or placebo (PBO) + TCS (rerandomized at week 16 to upadacitinib + TCS). Safety and efficacy, including proportion of patients experiencing ≥75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement ≥2 grades (vIGA-AD 0/1), and WP-NRS improvement ≥4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19).RESULTS: Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement ≥4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (≤0.2/100 patient-years).CONCLUSIONS: Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD.

KW - Administration, Topical

KW - Adolescent

KW - Adrenal Cortex Hormones/administration & dosage

KW - Adult

KW - Aged

KW - Child

KW - Dermatitis, Atopic/drug therapy

KW - Dermatologic Agents/administration & dosage

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Female

KW - Heterocyclic Compounds, 3-Ring/administration & dosage

KW - Humans

KW - Male

KW - Middle Aged

KW - Severity of Illness Index

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1016/j.jaci.2021.07.036

DO - 10.1016/j.jaci.2021.07.036

M3 - SCORING: Journal article

C2 - 34403658

VL - 149

SP - 977-987.e14

JO - J ALLERGY CLIN IMMUN

JF - J ALLERGY CLIN IMMUN

SN - 0091-6749

IS - 3

ER -