| Title: |
Dupilumab provides favourable long‐term safety and efficacy in children aged ≥ 6 to < 12 years with uncontrolled severe atopic dermatitis: results from an open‐label phase IIa study and subsequent phase III open‐label extension study |
| Authors: |
Cork, MJ; Thaçi, D; Eichenfield, LF; Arkwright, PD; Sun, X; Chen, Z; Akinlade, B; Boklage, S; Guillemin, I; Kosloski, MP; Kamal, MA; O’Malley, JT; Patel, N; Graham, NMH; Bansal, A |
| Source: |
British Journal of Dermatology, vol 184, iss 5 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2021 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); Clinical Research (rcdc); Orphan Drug (rcdc); Eczema / Atopic Dermatitis (rcdc); Rare Diseases (rcdc); Clinical Trials and Supportive Activities (rcdc); 6.1 Pharmaceuticals (hrcs-rac); 6.2 Cellular and gene therapies (hrcs-rac); Antibodies; Monoclonal; Humanized (mesh); Child (mesh); Cohort Studies (mesh); Dermatitis; Atopic (mesh); Double-Blind Method (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: |
857 - 870 |
| Description: |
BACKGROUND: Children aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16-week, randomized, placebo-controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)-4/IL-13 signalling, significantly improved signs and symptoms with acceptable safety; longer-term safety and efficacy data are lacking. OBJECTIVES: To report the pharmacokinetic profile and long-term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD. METHODS: Children (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study and subsequent open-label extension (OLE) study. Patients received single-dose dupilumab 2 or 4 mg kg-1 followed by 8-week pharmacokinetic sampling, then 2 or 4 mg kg-1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration-time profile and treatment-emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus Numeric Rating Scale (PP-NRS) score. RESULTS: Of 38 children enrolled, 37 completed phase IIa and 33 continued to the OLE. Nonlinear, target-mediated pharmacokinetics characterized dupilumab concentrations (week 24-48 mean serum concentrations: 2 mg kg-1 , 61-77 mg L-1 ; 4 mg kg-1 , 143-181 mg L-1 ). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. The most commonly reported TEAEs were nasopharyngitis (2 mg kg-1 , 47%; 4 mg kg-1 , 56%) and AD exacerbation (29% and 13%, respectively). Single-dose dupilumab rapidly improved AD with further improvements through week 52. Mean EASI and PP-NRS improved by -37%/-33% and -17%/-20% at week 2 (phase IIa) and -92%/-84% and -70%/-58% at week 52 (OLE), respectively. CONCLUSIONS: These safety and efficacy results support the use of dupilumab as a continuous long-term treatment for children aged ≥ 6 to < 12 years ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt6xq251dw; https://escholarship.org/uc/item/6xq251dw; https://escholarship.org/content/qt6xq251dw/qt6xq251dw.pdf |
| DOI: |
10.1111/bjd.19460 |
| Availability: |
https://escholarship.org/uc/item/6xq251dw; https://escholarship.org/content/qt6xq251dw/qt6xq251dw.pdf; https://doi.org/10.1111/bjd.19460 |
| Rights: |
CC-BY-NC-ND |
| Accession Number: |
edsbas.88E05ADF |
| Database: |
BASE |