Cork, M.J. orcid.org/0000-0003-4428-2428, Thaçi, D., Eichenfield, L.F. et al. (19 more authors) (2020) 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. British Journal of Dermatology, 182 (1). pp. 85-96. ISSN 0007-0963
Abstract
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 efficacy data support long‐term use of dupilumab in this patient population.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Nov 2019 09:37 |
Last Modified: | 17 Dec 2021 10:27 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/bjd.18476 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:152862 |
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