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Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial - 10/10/20

Doi : 10.1016/j.jaad.2020.06.054 
Amy S. Paller, MD a, b, Elaine C. Siegfried, MD c, d, Diamant Thaçi, MD e, Andreas Wollenberg, MD, FAAAAI f, Michael J. Cork, MB, PhD g, Peter D. Arkwright, FRCPCH, DPhil h, Melinda Gooderham, MD i, j, k, Lisa A. Beck, MD l, Mark Boguniewicz, MD m, n, Lawrence Sher, MD, FAAP o, Jamie Weisman, MD p, John T. O'Malley, MD, PhD q, Naimish Patel, MD q, Megan Hardin, MD, MPH q, Neil M.H. Graham, MD r, Marcella Ruddy, MD r, Xian Sun, PhD r, John D. Davis, PhD r, Mohamed A. Kamal, PharmD, PhD r, Faisal A. Khokhar, MD r, David M. Weinreich, MD, MBA r, George D. Yancopoulos, MD, PhD r, Bethany Beazley, PhD r, Ashish Bansal, MD, MBA r, Brad Shumel, MD r,
a Northwestern University Feinberg School of Medicine, Chicago, Illinois 
b Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois 
c Saint Louis University, St. Louis, Missouri 
d Cardinal Glennon Children's Hospital, St. Louis, Missouri 
e Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany 
f Ludwig-Maximilian University, Munich, Germany 
g University of Sheffield, Sheffield, United Kingdom 
h Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, United Kingdom 
i Probity Medical Research, Peterborough, Ontario, Canada 
j SKiN Centre for Dermatology, Peterborough, Ontario, Canada 
k Queen's University, Kingston, Ontario, Canada 
l University of Rochester Medical Center, Rochester, New York 
m National Jewish Health, Denver, Colorado 
n University of Colorado School of Medicine, Denver, Colorado 
o Peninsula Research Associates, Rolling Hills Estates 
p Advanced Medical Research, PC, Atlanta, California 
q Sanofi, Cambridge, Massachusetts 
r Regeneron Pharmaceuticals, Inc, Tarrytown New York 

Reprint requests: Brad Shumel, MD, Regeneron Pharmaceuticals, Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591.Regeneron Pharmaceuticals, Inc777 Old Saw Mill River RdTarrytownNY10591 Twitter: @Regeneron

Abstract

Background

Children with severe atopic dermatitis (AD) have limited treatment options.

Objective

We report the efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6-11 years with severe AD inadequately controlled with topical therapies.

Methods

In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w, baseline weight <30 kg; 200 mg q2w, baseline weight ≥30 kg), or placebo; with concomitant medium-potency TCS.

Results

Both the q4w and q2w dupilumab + TCS regimens resulted in clinically meaningful and statistically significant improvement in signs, symptoms, and quality of life (QOL) versus placebo + TCS in all prespecified endpoints. For q4w, q2w, and placebo, 32.8%, 29.5%, and 11.4% of patients, respectively, achieved Investigator's Global Assessment scores of 0 or 1; 69.7%, 67.2%, and 26.8% achieved ≥75% improvement in Eczema Area and Severity Index scores; and 50.8%, 58.3%, and 12.3% achieved ≥4-point reduction in worst itch score. Response to therapy was weight-dependent: optimal dupilumab doses for efficacy and safety were 300 mg q4w in children <30 kg and 200 mg q2w in children ≥30 kg. Conjunctivitis and injection-site reactions were more common with dupilumab + TCS than with placebo + TCS.

Limitations

Short-term 16-week treatment period; severe AD only.

Conclusion

Dupilumab + TCS is efficacious and well tolerated in children with severe AD, significantly improving signs, symptoms, and QOL.

Le texte complet de cet article est disponible en PDF.

Key words : atopic dermatitis, children, dupilumab, pediatric, severe

Abbreviations used : AD, AE, BSA, CDLQI, DFI, EASI, EASI-50, EASI-75, EASI-90, FAS, IGA, NRS, POEM, QOL, TCS, TEAE


Plan


 Funding sources: This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing and editorial support was provided by Lauren D. Van Wassenhove, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc.
 Conflicts of interest: Dr Paller is or has been an investigator for AbbVie, Castle Creek, Eli Lilly, Galderma, Incyte, Janssen, Lenus, Leo, Novartis, Regeneron Pharmaceuticals, Inc, and Verrica; and a consultant for Almirall, Amgen, Asana, Boehringer Ingelheim, Castle Creek, Celgene, Dermavant, Dermira, Eli Lilly, Exicure, Forte, Galderma, Lenus, Leo, MEDA Corp, Meiji Seika, Novan, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi Genzyme, Sol-Gel, and UCB. Dr Siegfried is or has been a consultant for Dermavant, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, Inc, and Verrica; serves or has served on the data and safety monitoring board for GlaxoSmithKline, LEO Pharma, and Novan; and is or has been the principal investigator in clinical trials for Eli Lilly, Janssen, Regeneron Pharmaceuticals, Inc, Stiefel, and Verrica. Dr Thaçi is or has been a consultant, advisory board member, and/or investigator for AbbVie, Almirall, Amgen, Beiersdorf, Boehringer Ingelheim, Celgene, DS-Pharma, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Maruho, Medac, MorphoSys, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Samsung, Sandoz, Sanofi, Sun Pharma, and UCB. Dr Wollenberg is or has been an investigator for Beiersdorf, Eli Lilly, Galderma, LEO Pharma, MedImmune, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, and Sanofi Genzyme; a consultant for AbbVie, Almirall, Anacor, Eli Lilly, Galapagos, Galderma, LEO Pharma, MedImmune, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, and Sanofi Genzyme; and a recipient of research grants from Beiersdorf, LEO Pharma, and Pierre Fabre. Dr Cork is or has been an investigator and/or consultant for AbbVie, Astellas, Boots, Dermavant, Galapagos, Galderma, Hyphens Pharma, Johnson & Johnson, LEO Pharma, L'Oréal, Menlo Therapeutics, Novartis, Oxagen, Pfizer, Procter & Gamble, Reckitt Benckiser, Regeneron Pharmaceuticals, Inc, and Sanofi Genzyme. Dr Arkwright is or has been an investigator for Regeneron Pharmaceuticals, Inc, and an adviser for and recipient of research grants from Sanofi Genzyme. Dr Gooderham is or has been an investigator, adviser, and/or speaker for AbbVie, Akros, Amgen, Arcutis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus BioSciences, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Merck, Medimmune, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Roche, Sanofi Genzyme, Sun Pharma, UCB, and Valeant/Bausch. Dr Beck is or has been an investigator and consultant for Regeneron Pharmaceuticals, Inc; receives or has received consulting fees or honoraria from AbbVie, Allakos, Arena Pharma, AstraZeneca, Connect Biopharma, Eli Lilly, LEO Pharma, Novan, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi, UCB, Vimalan; is or has been an investigator for AbbVie, LEO Pharma, and Pfizer; and owns stock in Medtronic and Pfizer. Dr Boguniewicz is or has been a consultant for and recipient of research grants and lecture honoraria from Regeneron Pharmaceuticals, Inc, and Sanofi; and is or has been a consultant for Eli Lilly. Dr Sher serves or has served as an advisory board member with Aimmune, Optinose, Regeneron Pharmaceuticals, Inc, and Sanofi Genzyme; receives or has received speaker fees from Regeneron Pharmaceuticals, Inc, and Sanofi Genzyme; and received clinical trials funding from Aimmune, Amgen, AstraZeneca, Circassia, DBV, Galderma, GlaxoSmithKline, Lupin, Merck, Mylan, Novartis, Novo Nordisk, Optinose, Pearl, Pfizer, Pulmagen, Roxane, Sanofi, Spirometrix, Teva, Vectura, and Watson. Dr Weisman is or has been a recipient of research grants from AbbVie, Allergan, Amgen, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, and UCB; and serves or has served as an advisory board member or on speakers' bureaus for AbbVie, Eli Lilly, Janssen, Regeneron Pharmaceuticals, Inc, and UCB. Drs O'Malley, Patel, and Hardin are employees of Sanofi and may hold stock or stock options in the company. Drs Graham, Ruddy, Sun, Davis, Kamal, Khokhar, Weinreich, Yancopoulos, Beazley, Bansal, and Shumel are employees of Regeneron Pharmaceuticals, Inc, and may hold stock or stock options in the company.
 IRB approval: This study was approved by multiple institutional review boards and ethics committees.
 Prior presentation: These data were accepted for presentation at the American Academy of Dermatology 78th Annual Meeting (March 20, 2020), which was canceled; however, abstracts will be published.


© 2020  American Academy of Dermatology, Inc.. Publié par Elsevier Masson SAS. Tous droits réservés.
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P. 1282-1293 - novembre 2020 Retour au numéro
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