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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
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 a...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247037/ https://www.ncbi.nlm.nih.gov/pubmed/32969489 http://dx.doi.org/10.1111/bjd.19460 |
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author | Cork, M.J. Thaçi, D. Eichenfield, L.F. Arkwright, P.D. Sun, X. Chen, Z. Akinlade, B. Boklage, S. Guillemin, I. Kosloski, M.P. Kamal, M.A. O’Malley, J.T. Patel, N. Graham, N.M.H. Bansal, A. |
author_facet | Cork, M.J. Thaçi, D. Eichenfield, L.F. Arkwright, P.D. Sun, X. Chen, Z. Akinlade, B. Boklage, S. Guillemin, I. Kosloski, M.P. Kamal, M.A. O’Malley, J.T. Patel, N. Graham, N.M.H. Bansal, A. |
author_sort | Cork, M.J. |
collection | PubMed |
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 with severe AD. |
format | Online Article Text |
id | pubmed-8247037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82470372021-07-02 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 Cork, M.J. Thaçi, D. Eichenfield, L.F. Arkwright, P.D. Sun, X. Chen, Z. Akinlade, B. Boklage, S. Guillemin, I. Kosloski, M.P. Kamal, M.A. O’Malley, J.T. Patel, N. Graham, N.M.H. Bansal, A. Br J Dermatol Original Articles 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 with severe AD. John Wiley and Sons Inc. 2020-10-09 2021-05 /pmc/articles/PMC8247037/ /pubmed/32969489 http://dx.doi.org/10.1111/bjd.19460 Text en © 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Cork, M.J. Thaçi, D. Eichenfield, L.F. Arkwright, P.D. Sun, X. Chen, Z. Akinlade, B. Boklage, S. Guillemin, I. Kosloski, M.P. Kamal, M.A. O’Malley, J.T. Patel, N. Graham, N.M.H. Bansal, A. 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 |
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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247037/ https://www.ncbi.nlm.nih.gov/pubmed/32969489 http://dx.doi.org/10.1111/bjd.19460 |
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