Safety and Efficacy of Upadacitinib for Atopic Dermatitis in Japan: Analysis of the 3-Year Phase 3 Rising Up Study

• Published in: Dermatology and therapy Vol. 14; no. 1; pp. 213 - 232
• Main Authors: Katoh, Norito, Ikeda, Masanori, Ohya, Yukihiro, Murota, Hiroyuki, Hu, Xiaofei, Liu, John, Niiyama, Hayato, Sasaki, Takuya, Raymundo, Eliza M., Saeki, Hidehisa
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.01.2024; Springer; Adis, Springer Healthcare
• Subjects: Atopic dermatitis; Clinical trial; Dermatology; Drug therapy; Eczema; Internal Medicine; Janus kinase inhibitors; Medicine; Medicine & Public Health; NCT; NCT03661138; Oral and Maxillofacial Surgery; Original Research; Patient outcomes; Plastic Surgery; Quality of Life Research; Safety; Topical corticosteroids; Japan; Topical corticosteroids; Atopic dermatitis; Janus kinase inhibitors; Eczema; Clinical trial; Safety; Upadacitinib
• ISSN: 2193-8210; 2190-9172
• DOI: 10.1007/s13555-023-01071-2

Introduction Upadacitinib is an oral Janus kinase inhibitor approved in multiple countries for moderate-to-severe atopic dermatitis (AD). Here we present long-term data for up to 3 years of continuous upadacitinib treatment in Japanese patients with AD. Methods Rising Up was a phase 3, randomized, multicenter study in Japan investigating the safety and efficacy of upadacitinib in patients with moderate-to-severe AD. Patients aged 12–75 years (weight ≥ 40 kg if < 18 years) were randomized 1:1:1 to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo through week 16 (all in combination with topical corticosteroids). At week 16, patients who received placebo were rerandomized 1:1 to upadacitinib 15 mg or 30 mg; topical corticosteroids were optional per investigator discretion from weeks 16–160. Safety was assessed by monitoring adverse events (AEs). Efficacy assessments included patients who achieved ≥ 75%/≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), clear/almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), or a ≥ 4-point improvement from baseline in Worst Pruritus Numerical Rating Scale (WP-NRS). Results Of 272 patients enrolled, 230 completed the study. Through week 160, the long-term incidence rate of overall AEs was numerically higher with upadacitinib 30 mg than 15 mg; rates of serious AEs, AEs considered possibly related to study drug, AEs leading to discontinuation, and AEs of special interest were generally low and similar between dose groups. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were generally greater with upadacitinib 30 mg than 15 mg and maintained through week 160 with either dose. Conclusion For up to 3 years of continuous treatment, upadacitinib was well tolerated in Japanese patients, with a similar safety profile to that of short-term studies and durable long-term response rates for skin clearance and itch improvement. Trial Registration ClinicalTrials.gov identifier, NCT03661138.