Efficacy, Safety, and Long-Term Disease Control of Ruxolitinib Cream Among Adolescents with Atopic Dermatitis: Pooled Results from Two Randomized Phase 3 Studies.
| Title: | Efficacy, Safety, and Long-Term Disease Control of Ruxolitinib Cream Among Adolescents with Atopic Dermatitis: Pooled Results from Two Randomized Phase 3 Studies. |
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| Authors: | Eichenfield LF; Departments of Dermatology and Pediatrics, University of California San Diego, San Diego, CA, USA. leichenfield@gmail.com.; Rady Children's Hospital, 3020 Children's Way, Mail Code 5092, San Diego, CA, 92123, USA. leichenfield@gmail.com.; Simpson EL; Oregon Health and Science University, Portland, OR, USA.; Papp K; Alliance Clinical Trials and Probity Medical Research, Waterloo, ON, Canada.; Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada.; Szepietowski JC; Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland.; Blauvelt A; Oregon Medical Research Center, Portland, OR, USA.; Kircik L; Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Silverberg JI; George Washington University, Washington, DC, USA.; Siegfried EC; Saint Louis University, St. Louis, MO, USA.; Kuligowski ME; Incyte Corporation, Wilmington, DE, USA.; Venturanza ME; Incyte Corporation, Wilmington, DE, USA.; Kallender H; Incyte Corporation, Wilmington, DE, USA.; Ren H; Incyte Corporation, Wilmington, DE, USA.; Paller AS; Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. |
| Source: | American journal of clinical dermatology [Am J Clin Dermatol] 2024 Jul; Vol. 25 (4), pp. 669-683. Date of Electronic Publication: 2024 May 02. |
| Publication Type: | Journal Article; Randomized Controlled Trial; Clinical Trial, Phase III |
| Language: | English |
| Journal Info: | Publisher: Adis, Springer International Country of Publication: New Zealand NLM ID: 100895290 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1179-1888 (Electronic) Linking ISSN: 11750561 NLM ISO Abbreviation: Am J Clin Dermatol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Auckland : Adis, Springer International; Original Publication: Auckland ; Philadelphia : Adis International, c2000- |
| MeSH Terms: | Pyrazoles*/administration & dosage ; Pyrazoles*/adverse effects ; Pyrimidines*/administration & dosage ; Pyrimidines*/adverse effects ; Dermatitis, Atopic*/drug therapy ; Dermatitis, Atopic*/diagnosis ; Skin Cream*/administration & dosage ; Nitriles* ; Severity of Illness Index*; Pruritus/etiology ; Pruritus/drug therapy ; Janus Kinase Inhibitors/administration & dosage ; Janus Kinase Inhibitors/adverse effects ; Janus Kinase Inhibitors/therapeutic use ; Janus Kinase 1/antagonists & inhibitors ; Humans ; Adolescent ; Female ; Male ; Child ; Treatment Outcome ; Administration, Cutaneous ; Double-Blind Method ; Time Factors |
| Abstract: | Background: Atopic dermatitis (AD), a highly pruritic, inflammatory skin disease, affects approximately 7% of adolescents globally. A topical formulation of ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated safety and efficacy among adolescents/adults in two phase 3 studies (TRuE-AD1/TRuE-AD2).; Objective: To describe safety and efficacy of 1.5% ruxolitinib cream versus vehicle and long-term disease control of ruxolitinib cream among adolescents aged 12-17 years from pooled phase 3 study data.; Methods: Patients [≥ 12 years old with AD for ≥ 2 years, Investigator's Global Assessment score (IGA) 2/3, and 3-20% affected body surface area (BSA) at baseline] were randomized 2:2:1 to ruxolitinib cream (0.75%/1.5%) or vehicle for 8 weeks of continuous use followed by a long-term safety (LTS) period up to 52 weeks with as-needed use. Patients originally applying vehicle were rerandomized 1:1 to 0.75%/1.5% ruxolitinib cream. Efficacy measures at week 8 included IGA treatment success (IGA-TS; i.e., score of 0/1 with ≥ 2 grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index (EASI-75), and ≥ 4-point improvement in itch numerical rating scale (NRS4). Measures of disease control during the LTS period included IGA score of 0 (clear) or 1 (almost clear) and percentage affected BSA. Safety was assessed throughout the study.; Results: Of 1249 randomized patients, 245 (19.6%) were aged 12-17 years. Of these, 45 patients were randomized to vehicle and 92 patients to 1.5% ruxolitinib cream. A total of 104/137 (75.9%) patients continued on 1.5% ruxolitinib cream in the LTS period [82/92 (89.1%) continued on 1.5% ruxolitinib cream; 22/45 (48.9%) patients on vehicle were reassigned to 1.5% ruxolitinib cream], and 83/104 (79.8%) of these patients completed the LTS period. At week 8, substantially more patients who applied 1.5% ruxolitinib cream versus vehicle achieved IGA-TS (50.6% versus 14.0%), EASI-75 (60.9% versus 34.9%), and NRS4 (52.1% versus 17.4%; P = 0.009). The mean (SD) reduction in itch NRS scores was significantly greater in patients applying 1.5% ruxolitinib cream versus vehicle from day 2 [- 0.9 (1.9) versus -0.2 (1.4); P = 0.03]. During the LTS period, mean (SD) trough steady-state ruxolitinib plasma concentrations at weeks 12/52 were 27.2 (55.7)/15.5 (31.5) nM. The percentage of patients achieving IGA score of 0 or 1 was sustained or further increased with 1.5% ruxolitinib cream; mean affected BSA was generally low (< 3%; i.e., mild disease). Through 52 weeks, application site reactions occurred in 1.8% of adolescent patients applying 1.5% ruxolitinib cream at any time; no patients had serious adverse events. There were no serious infections, malignancies, major adverse cardiovascular events, or thromboembolic events.; Conclusions: Meaningful anti-inflammatory and antipruritic effects were demonstrated with 1.5% ruxolitinib cream in the subset of adolescent patients with AD, comparable with those observed in the overall study population; long-term, as-needed use maintained disease control and was well tolerated.; Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03745638 (registered 19 November 2018) and NCT03745651 (registered 19 November 2018).; (© 2024. The Author(s).) |
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| Molecular Sequence: | ClinicalTrials.gov NCT03745638; NCT03745651 |
| Substance Nomenclature: | 82S8X8XX8H (ruxolitinib); 0 (Nitriles); 0 (Pyrazoles); 0 (Pyrimidines); 0 (Janus Kinase Inhibitors); EC 2.7.10.2 (Janus Kinase 1) |
| Entry Date(s): | Date Created: 20240502 Date Completed: 20240622 Latest Revision: 20250213 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11193693 |
| DOI: | 10.1007/s40257-024-00855-2 |
| PMID: | 38698175 |
| Database: | MEDLINE |
Journal Article; Randomized Controlled Trial; Clinical Trial, Phase III