PMID- 38127188 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240217 IS - 2193-8210 (Print) IS - 2190-9172 (Electronic) VI - 14 IP - 1 DP - 2024 Jan TI - Safety and Efficacy of Upadacitinib for Atopic Dermatitis in Japan: Analysis of the 3-Year Phase 3 Rising Up Study. PG - 213-232 LID - 10.1007/s13555-023-01071-2 [doi] AB - 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. CI - (c) 2023. The Author(s). FAU - Katoh, Norito AU - Katoh N AD - Department of Dermatology, Kyoto Prefectural University, Kyoto, Japan. FAU - Ikeda, Masanori AU - Ikeda M AD - Okayama University School of Medicine, Okayama, Japan. AD - Department of Pediatrics, Fukuyama Municipal Hospital, Hiroshima, Japan. FAU - Ohya, Yukihiro AU - Ohya Y AD - Allergy Center, National Center for Child Health and Development, Tokyo, Japan. FAU - Murota, Hiroyuki AU - Murota H AD - Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. FAU - Hu, Xiaofei AU - Hu X AD - AbbVie Inc., 1 North Waukegan Road, Dept R086, Bldg AP31-2, North Chicago, IL, 60064, USA. FAU - Liu, John AU - Liu J AD - AbbVie Inc., 1 North Waukegan Road, Dept R086, Bldg AP31-2, North Chicago, IL, 60064, USA. FAU - Niiyama, Hayato AU - Niiyama H AD - AbbVie GK, Tokyo, Japan. FAU - Sasaki, Takuya AU - Sasaki T AD - AbbVie GK, Tokyo, Japan. FAU - Raymundo, Eliza M AU - Raymundo EM AD - AbbVie Inc., 1 North Waukegan Road, Dept R086, Bldg AP31-2, North Chicago, IL, 60064, USA. eliza.raymundo@abbvie.com. FAU - Saeki, Hidehisa AU - Saeki H AD - Department of Dermatology, Nippon Medical School, Tokyo, Japan. LA - eng SI - ClinicalTrials.gov/NCT03661138 PT - Journal Article DEP - 20231221 PL - Switzerland TA - Dermatol Ther (Heidelb) JT - Dermatology and therapy JID - 101590450 PMC - PMC10828480 OTO - NOTNLM OT - Atopic dermatitis OT - Clinical trial OT - Eczema OT - Janus kinase inhibitors OT - Safety OT - Topical corticosteroids OT - Upadacitinib COIS- N. Katoh has received honoraria as a speaker/consultant for AbbVie, Celgene Japan, Eli Lilly Japan, Janssen Pharma, Kyowa Kirin, LEO Pharma, Maruho, Pfizer, Sanofi, and Taiho Pharmaceutical. He has received grants as an investigator from AbbVie, A2 Healthcare, Boehringer Ingelheim Japan, Janssen Pharma, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Sun Pharma, and Torii Pharmaceutical. M. Ikeda has received a scholarship donation from the Central Research Institute of Pias. He has participated in clinical studies and/or has received honoraria as a speaker/consultant for AbbVie, AstraZeneca, Eli Lilly, GlaxoSmithKline, Hisamitsu, Maruho, MedImmune, Novo Nordisk, Pfizer, Sanofi, and Yanssen Pharmaceutical. Y. Ohya has received honoraria as a speaker, consultant, and/or for data safety monitoring for AbbVie, Japan Tobacco, Kao, Maruho, Mitsubishi Tanabe Pharma, Nobel Pharma, Otsuka Pharmaceutical, Pfizer, Pierre Fabre, Sanofi/Regeneron, Shino-Test, Sysmex, Torii Pharmaceutical, and Towa Pharmaceutical. He has received grants as an investigator from Fam's. H. Murota has received funding or grant support from Maruho, Mitsubishi Tanabe Pharma, and SUN Pharma. He has received honorarium as a speaker/consultant from AbbVie, Kaken Pharmaceutical, Lilly, Maruho, Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical, Pfizer, Sanofi, Shiseido Japan, Taiho Pharmaceutical, and Torii Pharmaceutical. X. Hu, H. Niiyama, T. Sasaki, and E.M. Raymundo are current full-time employees of AbbVie Inc., and may hold AbbVie stock and/or stock options. J. Liu is a former (retired) employee of AbbVie Inc., and may hold AbbVie stock and/or stock options. H. Saeki has received honoraria for consultancy from AbbVie, Amgen, Japan Tobacco, LEO Pharma, Lilly Japan, Maruho, Mitsubishi Tanabe Pharma, Novartis, Otsuka Pharmaceutical, Pfizer, Japan, Sanofi, Taiho Pharmaceutical, and Torii Pharmaceutical. He has received funding/grant support from Eisai, Maruho, Taiho Pharmaceutical, Tokiwa Pharmaceutical, and Torii Pharmaceutical. EDAT- 2023/12/21 12:41 MHDA- 2023/12/21 12:42 PMCR- 2023/12/21 CRDT- 2023/12/21 11:24 PHST- 2023/09/19 00:00 [received] PHST- 2023/11/09 00:00 [accepted] PHST- 2023/12/21 12:42 [medline] PHST- 2023/12/21 12:41 [pubmed] PHST- 2023/12/21 11:24 [entrez] PHST- 2023/12/21 00:00 [pmc-release] AID - 10.1007/s13555-023-01071-2 [pii] AID - 1071 [pii] AID - 10.1007/s13555-023-01071-2 [doi] PST - ppublish SO - Dermatol Ther (Heidelb). 2024 Jan;14(1):213-232. doi: 10.1007/s13555-023-01071-2. Epub 2023 Dec 21.