A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysisCapsule Summary
Background: Systemic atopic dermatitis treatments that have acceptable safety are needed. Objective: To evaluate the safety of the oral Janus kinase inhibitor upadacitinib in combination with topical corticosteroids (TCSs) for the treatment of atopic dermatitis. Methods: In this phase 3, double-blin...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-03-01
|
| Series: | JAAD International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666328721000894 |
| _version_ | 1818986945603174400 |
|---|---|
| author | Norito Katoh, MD, PhD Yukihiro Ohya, MD, PhD Hiroyuki Murota, MD, PhD Masanori Ikeda, MD, PhD Xiaofei Hu, PhD Kimitoshi Ikeda, PhD John Liu, MD, MS Takuya Sasaki Alvina D. Chu, MD Henrique D. Teixeira, PhD, MBA Hidehisa Saeki, MD, PhD |
| author_facet | Norito Katoh, MD, PhD Yukihiro Ohya, MD, PhD Hiroyuki Murota, MD, PhD Masanori Ikeda, MD, PhD Xiaofei Hu, PhD Kimitoshi Ikeda, PhD John Liu, MD, MS Takuya Sasaki Alvina D. Chu, MD Henrique D. Teixeira, PhD, MBA Hidehisa Saeki, MD, PhD |
| author_sort | Norito Katoh, MD, PhD |
| collection | DOAJ |
| description | Background: Systemic atopic dermatitis treatments that have acceptable safety are needed. Objective: To evaluate the safety of the oral Janus kinase inhibitor upadacitinib in combination with topical corticosteroids (TCSs) for the treatment of atopic dermatitis. Methods: In this phase 3, double-blind study (Rising Up), Japanese patients (12-75 years) with moderate-to-severe atopic dermatitis were randomized in a 1:1:1 ratio to receive 15 mg of upadacitinib + TCS, 30 mg of upadacitinib + TCS, or a placebo + TCS (rerandomized in a 1:1 ratio to receive either 15 or 30 mg of upadacitinib + TCS at week 16). Adverse events and laboratory data were assessed for safety. Results: In 272 treated patients, the serious adverse event rates were similar for 15- and 30-mg upadacitinib + TCS at week 24 (15 mg, 56%; 30 mg, 64%) but greater than those for placebo + TCS (42%). Acne (all mild or moderate; none leading to discontinuation) occurred more frequently with upadacitinib + TCS (15 mg, 13.2%; 30 mg, 19.8%) than with placebo + TCS (5.6%). Furthermore, herpes zoster infection (4.4% vs 0%), anemia (1.1% vs 0%), neutropenia (4.4% vs 1.1%), and creatine phosphokinase elevations (2.2% vs 1.1%) occurred more frequently with 30-mg upadacitinib + TCS than with 15-mg upadacitinib + TCS; none of these events were reported with placebo + TCS. No thromboembolic events, malignancies, gastrointestinal perforations, active tuberculosis, or deaths occurred. Limitations: The limitations included a small sample size and short observation period as well as nongeneralizability of the results beyond Japanese populations. Conclusions: The results were generally consistent with those of previous reports; no new safety risks were detected. |
| first_indexed | 2024-12-20T18:58:51Z |
| format | Article |
| id | doaj.art-3381acdcae8e440badf8a810bf6ba5e2 |
| institution | Directory Open Access Journal |
| issn | 2666-3287 |
| language | English |
| last_indexed | 2024-12-20T18:58:51Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JAAD International |
| spelling | doaj.art-3381acdcae8e440badf8a810bf6ba5e22022-12-21T19:29:26ZengElsevierJAAD International2666-32872022-03-0162736A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysisCapsule SummaryNorito Katoh, MD, PhD0Yukihiro Ohya, MD, PhD1Hiroyuki Murota, MD, PhD2Masanori Ikeda, MD, PhD3Xiaofei Hu, PhD4Kimitoshi Ikeda, PhD5John Liu, MD, MS6Takuya Sasaki7Alvina D. Chu, MD8Henrique D. Teixeira, PhD, MBA9Hidehisa Saeki, MD, PhD10Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, JapanAllergy Center, National Center for Child Health and Development, Tokyo, JapanDepartment of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; Fukuyama Municipal Hospital, Hiroshima, JapanAbbVie Inc, North Chicago, IllinoisAbbVie GK, Tokyo, JapanAbbVie Inc, North Chicago, IllinoisAbbVie GK, Tokyo, JapanAbbVie Inc, North Chicago, IllinoisAbbVie Inc, North Chicago, Illinois; Correspondence to: Henrique D. Teixeira, PhD, MBA, AbbVie, Inc, 1 North Waukegan Road, Dept. R086, Bldg. AP31-2, North Chicago, IL 60064.Department of Dermatology, Nippon Medical School, Tokyo, JapanBackground: Systemic atopic dermatitis treatments that have acceptable safety are needed. Objective: To evaluate the safety of the oral Janus kinase inhibitor upadacitinib in combination with topical corticosteroids (TCSs) for the treatment of atopic dermatitis. Methods: In this phase 3, double-blind study (Rising Up), Japanese patients (12-75 years) with moderate-to-severe atopic dermatitis were randomized in a 1:1:1 ratio to receive 15 mg of upadacitinib + TCS, 30 mg of upadacitinib + TCS, or a placebo + TCS (rerandomized in a 1:1 ratio to receive either 15 or 30 mg of upadacitinib + TCS at week 16). Adverse events and laboratory data were assessed for safety. Results: In 272 treated patients, the serious adverse event rates were similar for 15- and 30-mg upadacitinib + TCS at week 24 (15 mg, 56%; 30 mg, 64%) but greater than those for placebo + TCS (42%). Acne (all mild or moderate; none leading to discontinuation) occurred more frequently with upadacitinib + TCS (15 mg, 13.2%; 30 mg, 19.8%) than with placebo + TCS (5.6%). Furthermore, herpes zoster infection (4.4% vs 0%), anemia (1.1% vs 0%), neutropenia (4.4% vs 1.1%), and creatine phosphokinase elevations (2.2% vs 1.1%) occurred more frequently with 30-mg upadacitinib + TCS than with 15-mg upadacitinib + TCS; none of these events were reported with placebo + TCS. No thromboembolic events, malignancies, gastrointestinal perforations, active tuberculosis, or deaths occurred. Limitations: The limitations included a small sample size and short observation period as well as nongeneralizability of the results beyond Japanese populations. Conclusions: The results were generally consistent with those of previous reports; no new safety risks were detected.http://www.sciencedirect.com/science/article/pii/S2666328721000894atopic dermatitisclinical trialeczemaJanus kinase inhibitorssafetytopical corticosteroids |
| spellingShingle | Norito Katoh, MD, PhD Yukihiro Ohya, MD, PhD Hiroyuki Murota, MD, PhD Masanori Ikeda, MD, PhD Xiaofei Hu, PhD Kimitoshi Ikeda, PhD John Liu, MD, MS Takuya Sasaki Alvina D. Chu, MD Henrique D. Teixeira, PhD, MBA Hidehisa Saeki, MD, PhD A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysisCapsule Summary JAAD International atopic dermatitis clinical trial eczema Janus kinase inhibitors safety topical corticosteroids |
| title | A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysisCapsule Summary |
| title_full | A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysisCapsule Summary |
| title_fullStr | A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysisCapsule Summary |
| title_full_unstemmed | A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysisCapsule Summary |
| title_short | A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysisCapsule Summary |
| title_sort | phase 3 randomized multicenter double blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate to severe atopic dermatitis in japan rising up an interim 24 week analysiscapsule summary |
| topic | atopic dermatitis clinical trial eczema Janus kinase inhibitors safety topical corticosteroids |
| url | http://www.sciencedirect.com/science/article/pii/S2666328721000894 |
| work_keys_str_mv | AT noritokatohmdphd aphase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT yukihiroohyamdphd aphase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT hiroyukimurotamdphd aphase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT masanoriikedamdphd aphase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT xiaofeihuphd aphase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT kimitoshiikedaphd aphase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT johnliumdms aphase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT takuyasasaki aphase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT alvinadchumd aphase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT henriquedteixeiraphdmba aphase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT hidehisasaekimdphd aphase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT noritokatohmdphd phase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT yukihiroohyamdphd phase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT hiroyukimurotamdphd phase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT masanoriikedamdphd phase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT xiaofeihuphd phase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT kimitoshiikedaphd phase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT johnliumdms phase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT takuyasasaki phase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT alvinadchumd phase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT henriquedteixeiraphdmba phase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary AT hidehisasaekimdphd phase3randomizedmulticenterdoubleblindstudytoevaluatethesafetyofupadacitinibincombinationwithtopicalcorticosteroidsinadolescentandadultpatientswithmoderatetosevereatopicdermatitisinjapanrisingupaninterim24weekanalysiscapsulesummary |