TY - JOUR
T1 - Laboratory Safety of Dupilumab in Patients Aged 6–11 Years with Severe Atopic Dermatitis
T2 - Results from a Phase III Clinical Trial
AU - Paller, Amy S.
AU - Wollenberg, Andreas
AU - Siegfried, Elaine
AU - Thaçi, Diamant
AU - Cork, Michael J.
AU - Arkwright, Peter D.
AU - Gooderham, Melinda
AU - Sun, Xian
AU - O’Malley, John T.
AU - Khokhar, Faisal A.
AU - Vakil, Jignesh
AU - Bansal, Ashish
AU - Rosner, Karli
AU - Shumel, Brad
AU - Levit, Noah A.
N1 - Funding Information:
Amy S. Paller has served as a scientific advisor and/or clinical study investigator for AbbVie, Abeona Therapeutics, Almirall, AnaptysBio, Asana Biosciences, Boehringer Ingelheim, BridgeBio, Dermavant, Dermira, Eli Lilly, Exicure, Forté, Galderma, Incyte, InMed Pharmaceuticals, Janssen, LEO Pharma, LifeMax, Novartis, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Sol Gel, and UCB. Andreas Wollenberg has been an investigator for Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, and UCB; has been a consultant for AbbVie, Almirall, Anacor Pharmaceuticals, Arena Pharmaceuticals, Eli Lilly, Galapagos, Galderma, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., and Sanofi Genzyme; and has received research grants from LEO Pharma and Pierre Fabre. Elaine Siegfried has served as a scientific advisor and/or clinical study investigator for Eli Lilly, Janssen, Novan, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, UCB, and Verrica Pharmaceuticals; as a paid speaker for Regeneron Pharmaceuticals, Inc.; and as a data and safety monitoring board member for GSK, LEO Pharma, Novan, Pfizer, and UCB. Diamant Thaçi has been a consultant, advisory board member, and/or investigator for AbbVie, Almirall, Amgen, Beiersdorf, Boehringer Ingelheim, Dermira, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, and UCB. Michael J. Cork has received research grants from Astellas Pharma, Atopix, Galopagos, Harvey Water Softeners, Hyphens Pharma, Johnson & Johnson, Kymab, L’Oréal, LEO Pharma, Novartis, Oxagen, Perrigo (ACO Nordic), Pfizer, Reckitt Benkiser, Regeneron Pharmaceuticals, Inc., and Sanofi Genzyme; has been a consultant and/or advisory board member for Astellas Pharma, Atopix, Boots, Dermavent, Galderma, Galopagos, Hyphens Pharma, Johnson & Johnson, Kymab, L’Oréal, LEO Pharma, Menlo, Novartis, Oxagen, Perrigo (ACO Nordic), Pfizer, Proctor & Gamble, Reckitt Benkiser, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, and UCB; and has served as a voluntary medical advisor to the National Eczema Society, UK. Peter D. Arkwright has served as an advisory board member for and received consulting fees and project grant funding from Sanofi Genzyme; and is an investigator for Regeneron Pharmaceuticals, Inc. Melinda Gooderham has received consulting fees/honoraria from AbbVie, Akros Pharma, Amgen, Arcutis Biotherapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Coherus BioSciences, Dermira, Eli Lilly, Galderma, GSK, Janssen, Kyowa Kirin, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Sun Pharma, UCB, and Valeant Pharmaceuticals/Bausch; has received fees for participation in review activities from AbbVie, Akros Pharma, Amgen, Arcutis Biotherapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Kyowa Kirin, LEO Pharma, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, UCB, and Valeant Pharmaceuticals/Bausch; has received payment for lectures and/or service on speakers bureaus from AbbVie, Amgen, Biosciences, Boehringer Ingelheim, Dermira, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Sun Pharma, UCB, and Valeant Pharmaceuticals/Bausch; and has served as an investigator, advisor, and/or speaker for AbbVie, Akros Pharma, Amgen, Arcutis Biotherapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Coherus BioSciences, Dermira, Eli Lilly, Galderma, GSK, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Sanofi Genzyme, Sun Pharma, UCB, and Valeant Pharmaceuticals/Bausch. Xian Sun, Faisal A. Khokhar, Ashish Bansal, Brad Shumel, and Noah A. Levit are employees and shareholders of Regeneron Pharmaceuticals, Inc. John T. O’Malley and Jignesh Vakil are employees of and may hold stock and/or stock options in Sanofi. Karli Rosner is an employee of and may hold stock and/or stock options in Sanofi Genzyme.
Funding Information:
This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The authors thank the patients and their families for their participation in these studies, their colleagues for their support, and John Caminis, MD, Adriana Mello, PharmD, PGC Bus (of Sanofi), and Linda Williams, RPh (of Regeneron Pharmaceuticals, Inc.) for their contributions. Medical writing and editorial assistance were provided by Vicki Schwartz, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc.
Funding Information:
Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifier: NCT03345914. The study sponsors participated in the study design; collection, analysis, and interpretation of the data; writing of the report; and the decision to submit the article for publication. Medical writing/editorial assistance were provided by Vicki Schwartz, PhD, of Excerpta Medica, and was funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline: https://www.acpjournals.org/doi/10.7326/M15-0288 .
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/9
Y1 - 2021/9
N2 - 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: 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: 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: 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: 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: ClinicalTrials.gov Identifier: NCT03345914. Video abstract: [MediaObject not available: see fulltext.]
AB - 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: 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: 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: 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: 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: ClinicalTrials.gov Identifier: NCT03345914. Video abstract: [MediaObject not available: see fulltext.]
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U2 - 10.1007/s40272-021-00459-x
DO - 10.1007/s40272-021-00459-x
M3 - Article
C2 - 34462864
AN - SCOPUS:85113879828
SN - 1174-5878
VL - 23
SP - 515
EP - 527
JO - Pediatric Drugs
JF - Pediatric Drugs
IS - 5
ER -