| Title: |
Dupilumab in adolescents with uncontrolled moderate‐to‐severe atopic dermatitis: results from a phase IIa open‐label trial and subsequent phase III open‐label extension |
| Authors: |
Cork, MJ; Thaçi, D; Eichenfield, LF; Arkwright, PD; Hultsch, T; Davis, JD; Zhang, Y; Zhu, X; Chen, Z; Li, M; Ardeleanu, M; Teper, A; Akinlade, B; Gadkari, A; Eckert, L; Kamal, MA; Ruddy, M; Graham, NMH; Pirozzi, G; Stahl, N; DiCioccio, AT; Bansal, A |
| Source: |
British Journal of Dermatology, vol 182, iss 1 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2020 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); 3211 Oncology and Carcinogenesis (for-2020); Clinical Research (rcdc); Clinical Trials and Supportive Activities (rcdc); Eczema / Atopic Dermatitis (rcdc); 6.1 Pharmaceuticals (hrcs-rac); 6.2 Cellular and gene therapies (hrcs-rac); Skin (hrcs-hc); Adolescent (mesh); Antibodies; Monoclonal; Humanized (mesh); Cohort Studies (mesh); Dermatitis; Atopic (mesh); Double-Blind Method (mesh); Eczema (mesh); Humans (mesh); Severity of Illness Index (mesh); Treatment Outcome (mesh); 1103 Clinical Sciences (for); 1112 Oncology and Carcinogenesis (for); Dermatology & Venereal Diseases (science-metrix) |
| Subject Geographic: |
85 - 96 |
| Description: |
BACKGROUND: Dupilumab (monoclonal antibody inhibiting IL-4/IL-13 signalling) is approved for use in adolescents aged ≥ 12 years with inadequately controlled moderate-to-severe atopic dermatitis (AD). Dupilumab significantly improved AD signs/symptoms in a 16-week, randomised, placebo-controlled phase III trial in adolescents (NCT03054428). OBJECTIVES: To characterize the pharmacokinetics of dupilumab, and long-term safety and efficacy in adolescents. METHODS: This was a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study with a phase III open-label extension (OLE) in adolescents with moderate-to-severe AD. In the phase IIa study, patients received one dupilumab dose (2 mg kg-1 or 4 mg kg-1 ) and 8 weeks of pharmacokinetic sampling. Thereafter, patients received the same dose weekly for 4 weeks, with 8-week safety follow-up. Patients then enrolled in the OLE, continuing 2 mg kg-1 or 4 mg kg-1 dupilumab weekly. Primary end points were dupilumab concentration-time profile and incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included Eczema Area and Severity Index (EASI). RESULTS: Forty adolescents received dupilumab in the phase IIa study; 36 enrolled in the OLE. Dupilumab showed nonlinear, target-mediated pharmacokinetics. Mean ± SD trough dupilumab concentrations in serum at week 48 (OLE) were 74 ± 19 mg L-1 and 161 ± 60 mg L-1 for 2 mg kg-1 and 4 mg kg-1 , respectively. Dupilumab was well tolerated over 52 weeks; the most common TEAEs were nasopharyngitis (week 52: 41% [2 mg kg-1 ], 47% [4 mg kg-1 ]) and AD exacerbation (29%, 42%). After one dupilumab dose in the phase IIa study, EASI improved from baseline to week 2 [mean ± SD reduction -34% ± 20% (2 mg kg-1 ) and -51% ± 29% (4 mg kg-1 )]. With continuing treatment, EASI scores improved further [week 52: -85% ± 12% (2 mg kg-1 ) and -84% ± 20% (4 mg kg-1 )]. CONCLUSIONS: In adolescents with moderate-to-severe AD, dupilumab's pharmacokinetic profile was similar to that in adults. These 52-week safety and ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt9724r00b; https://escholarship.org/uc/item/9724r00b; https://escholarship.org/content/qt9724r00b/qt9724r00b.pdf |
| DOI: |
10.1111/bjd.18476 |
| Availability: |
https://escholarship.org/uc/item/9724r00b; https://escholarship.org/content/qt9724r00b/qt9724r00b.pdf; https://doi.org/10.1111/bjd.18476 |
| Rights: |
CC-BY-NC |
| Accession Number: |
edsbas.5104B689 |
| Database: |
BASE |