Laboratory Safety of Dupilumab in Patients Aged 6-11 Years with Severe Atopic Dermatitis: Results from a Phase III Clinical Trial.
Journal
Paediatric drugs
ISSN: 1179-2019
Titre abrégé: Paediatr Drugs
Pays: Switzerland
ID NLM: 100883685
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
accepted:
23
06
2021
pubmed:
1
9
2021
medline:
26
11
2021
entrez:
31
8
2021
Statut:
ppublish
Résumé
Previous studies of dupilumab in adolescents and adults with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful adverse changes in laboratory parameters. The aim of this study was to assess laboratory outcomes in children aged 6-11 years with severe AD in a randomized, placebo-controlled, phase III trial of dupilumab. Children aged 6-11 years with severe AD were randomized 1:1:1 to 16 weeks of dupilumab 300 mg every 4 weeks, 100 or 200 mg every 2 weeks, or matching placebo, all with concomitant topical corticosteroids (TCS). Blood samples were collected at baseline and Weeks 4, 8, and 16; urine samples were collected at baseline and Weeks 4 and 16. Of 367 patients enrolled in the study, 362 were included in the safety analysis, 351 completed study treatment, and 4 withdrew due to treatment-emergent adverse events not related to laboratory abnormalities. Both dupilumab + TCS groups showed overall trends toward increases in mean blood levels of eosinophils and alkaline phosphatase, and decreases in mean blood levels of platelets, neutrophils, and lactate dehydrogenase levels, without corresponding mean changes in the placebo + TCS group. None of these changes were associated with symptoms or clinically meaningful adverse outcomes, and none led to treatment modification. No clinically significant changes or trends were observed for other measured laboratory parameters. There were no clinically meaningful adverse changes in routine laboratory parameters attributable to treatment with dupilumab + TCS. Changes in platelet counts and lactate dehydrogenase levels likely reflect reduced inflammation. These results confirm similar findings in adults and adolescents, and suggest that there is no need for routine laboratory monitoring of children aged 6-11 years treated with dupilumab + TCS for severe AD. ClinicalTrials.gov Identifier: NCT03345914. Does treatment with dupilumab require routine laboratory monitoring in 6- to 11-year-old children with severe atopic dermatitis? (MP4 180482 kb).
Sections du résumé
BACKGROUND
BACKGROUND
Previous studies of dupilumab in adolescents and adults with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful adverse changes in laboratory parameters.
OBJECTIVE
OBJECTIVE
The aim of this study was to assess laboratory outcomes in children aged 6-11 years with severe AD in a randomized, placebo-controlled, phase III trial of dupilumab.
METHODS
METHODS
Children aged 6-11 years with severe AD were randomized 1:1:1 to 16 weeks of dupilumab 300 mg every 4 weeks, 100 or 200 mg every 2 weeks, or matching placebo, all with concomitant topical corticosteroids (TCS). Blood samples were collected at baseline and Weeks 4, 8, and 16; urine samples were collected at baseline and Weeks 4 and 16.
RESULTS
RESULTS
Of 367 patients enrolled in the study, 362 were included in the safety analysis, 351 completed study treatment, and 4 withdrew due to treatment-emergent adverse events not related to laboratory abnormalities. Both dupilumab + TCS groups showed overall trends toward increases in mean blood levels of eosinophils and alkaline phosphatase, and decreases in mean blood levels of platelets, neutrophils, and lactate dehydrogenase levels, without corresponding mean changes in the placebo + TCS group. None of these changes were associated with symptoms or clinically meaningful adverse outcomes, and none led to treatment modification. No clinically significant changes or trends were observed for other measured laboratory parameters.
CONCLUSION
CONCLUSIONS
There were no clinically meaningful adverse changes in routine laboratory parameters attributable to treatment with dupilumab + TCS. Changes in platelet counts and lactate dehydrogenase levels likely reflect reduced inflammation. These results confirm similar findings in adults and adolescents, and suggest that there is no need for routine laboratory monitoring of children aged 6-11 years treated with dupilumab + TCS for severe AD.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov Identifier: NCT03345914. Does treatment with dupilumab require routine laboratory monitoring in 6- to 11-year-old children with severe atopic dermatitis? (MP4 180482 kb).
Identifiants
pubmed: 34462864
doi: 10.1007/s40272-021-00459-x
pii: 10.1007/s40272-021-00459-x
pmc: PMC8418591
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
dupilumab
420K487FSG
Banques de données
ClinicalTrials.gov
['NCT03345914']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
515-527Informations de copyright
© 2021. The Author(s).
Références
Br J Dermatol. 2020 Jan;182(1):85-96
pubmed: 31595499
Allergol Int. 2019 Oct;68(4):430-436
pubmed: 31266709
Ann Allergy Asthma Immunol. 2018 Jan;120(1):10-22.e2
pubmed: 29273118
Lancet. 2019 Nov 2;394(10209):1638-1650
pubmed: 31543428
N Engl J Med. 2016 Dec 15;375(24):2335-2348
pubmed: 27690741
Br J Dermatol. 2018 Mar;178(3):768-775
pubmed: 28865094
Expert Rev Clin Immunol. 2017 May;13(5):425-437
pubmed: 28277826
J Adv Nurs. 2019 Jan;75(1):30-42
pubmed: 30109720
J Dermatol. 1990 Aug;17(8):477-81
pubmed: 2229651
Children (Basel). 2019 Nov 05;6(11):
pubmed: 31694234
N Engl J Med. 2018 Jun 28;378(26):2486-2496
pubmed: 29782217
JAMA Dermatol. 2020 Jan 1;156(1):44-56
pubmed: 31693077
Allergy. 2020 May;75(5):1188-1204
pubmed: 31838750
Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5153-8
pubmed: 24706856
Allergol Int. 2008 Dec;57(4):391-6
pubmed: 18797178
Nat Rev Drug Discov. 2016 Jan;15(1):35-50
pubmed: 26471366
Br J Dermatol. 2020 May;182(5):1120-1135
pubmed: 31407311
Eur J Intern Med. 2015 Sep;26(7):545-53
pubmed: 25971154
J Am Acad Dermatol. 2020 Nov;83(5):1282-1293
pubmed: 32574587
J Am Acad Dermatol. 2020 Feb;82(2):377-388
pubmed: 31374300
Br J Dermatol. 2018 May;178(5):1083-1101
pubmed: 29193016
J Allergy Clin Immunol. 2012 Dec;130(6):1344-54
pubmed: 22951056
J Am Acad Dermatol. 2019 Aug;81(2):510-519
pubmed: 31009665
N Engl J Med. 2018 Jun 28;378(26):2475-2485
pubmed: 29782224
J Dermatol Sci. 2015 Feb;77(2):93-101
pubmed: 25459165
Am J Clin Dermatol. 2021 Mar;22(2):243-255
pubmed: 33655423
J Eur Acad Dermatol Venereol. 2020 Dec;34(12):2717-2744
pubmed: 33205485
Lancet. 2017 Jun 10;389(10086):2287-2303
pubmed: 28478972
Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5147-52
pubmed: 24706858
J Am Acad Dermatol. 2003 Dec;49(6):1088-95
pubmed: 14639390