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

• Published in: Journal of allergy and clinical immunology 2022-03, Vol.149 (3), p.977-987.e14
• Main Authors: Silverberg, Jonathan I., de Bruin-Weller, Marjolein, Bieber, Thomas, Soong, Weily, Kabashima, Kenji, Costanzo, Antonio, Rosmarin, David, Lynde, Charles, Liu, John, Gamelli, Amy, Zeng, Jiewei, Ladizinski, Barry, Chu, Alvina D., Reich, Kristian
• Format: Article
• Language: English
• Subjects: Administration, Topical; Adolescent; Adrenal Cortex Hormones - administration & dosage; Adrenal Cortex Hormones - adverse effects; Adult; Aged; Atopic dermatitis; Child; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - pathology; Dermatologic Agents - administration & dosage; Dermatologic Agents - adverse effects; Double-Blind Method; Drug Therapy, Combination; Female; Heterocyclic Compounds, 3-Ring - administration & dosage; Heterocyclic Compounds, 3-Ring - adverse effects; Humans; Janus kinase inhibitors; Male; Middle Aged; randomized clinical trial; Severity of Illness Index; topical corticosteroids; Treatment Outcome; upadacitinib; Young Adult
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2021.07.036

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. We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks. 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). 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). 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.