Efficacy of Dupilumab in Different Racial Subgroups of Adults With Moderate-to-Severe Atopic Dermatitis in Three Randomized, Placebo-Controlled Phase 3 Trials
August 2019 | Volume 18 | Issue 8 | Original Article | 804 | Copyright © August 2019
Andrew F. Alexis MD MPH,a Marta Rendon MD,B Jonathan I. Silverberg MD,c David M. Pariser MD,D Benjamin Lockshin MD,e Christopher E.M. Griffiths MD,f Jamie Weisman MD,g Andreas Wollenberg MD,h Zhen Chen PhD,i John D. Davis PhD,i Meng Li PhD,j Laurent Eckert PhD,k Abhijit Gadkari PhD,i Brad Shumel MD,i Ana B. Rossi MD,l Neil M.H. Graham MD,i Marius Ardeleanu MDi
ªDepartment of Dermatology, Mount Sinai West, New York, NY
BRendon Center for Dermatology and Aesthetic Medicine, Boca Raton, FL
cDepartment of Dermatology, Preventive Medicine and Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL
DDepartment of Dermatology, Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA
EU.S. Dermatology Partners, Rockville, MD
fDermatology Centre NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester, UK
gAdvanced Medical Research, PC, Atlanta, GA
hDepartment of Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany
IRegeneron Pharmaceuticals, Inc., Tarrytown, NY
jSanofi, Bridgewater, NJ
kSanofi, Chilly-Mazarin, France
lSanofi Genzyme, Cambridge, MA
Co., Galderma, GSK, Incyte, Kiniksa, LEO Pharma, MedImmune (AstraZeneca), Menlo Therapeutics, Pfizer, Procter & Gamble, Realm, Regeneron Pharmaceuticals, Inc.; speaker for Regeneron Pharmaceuticals, Inc. David M. Pariser is a consultant, received honoraria from Bickel Biotechnology, Biofrontera, Celgene, Dermira, DUSA Pharmaceuticals, LEO Pharma, Novartis, Promius Pharma, Regeneron Pharmaceuticals, Inc., Sanofi, TheraVida, Inc., Valeant; principal investigator, received grants, research funding from Abbott Laboratories, Amgen, Asana BioSciences, Bickel Biotechnology, Celgene, Dermavant Sciences, Eli Lilly & Co., LEO Pharma, Merck & Co., Novartis, Novo Nordisk, Ortho Dermatologics, Peplin, Pfizer, Photocure ASA, Promius Pharma, Regeneron Pharmaceuticals, Inc., Stiefel/ GSK, Valeant; advisory board member, received honoraria from Pfizer; principal investigator, received honoraria from LEO Pharma, Pfizer; investigator, received grants, research funding from Promius Pharma. Benjamin Lockshin received honoraria and/or research grants from AbbVie, Celgene, Dermira, Eli Lilly & Co., Franklin Bioscience, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, Sun Pharmaceutical Industries. Christopher E.M. Griffiths received honoraria and/or research grants from AbbVie, Almirall, Eli Lilly & Co., Janssen, LEO Pharma, Merck & Co., Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Sandoz, Sanofi, Sun Pharmaceutical Industries, Ltd., UCB Pharma. Jamie Weisman received research grants from AbbVie, Allergan, Amgen, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly & Co., Galderma, GSK, Janssen, LEO Pharma, Merck & Co., Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., UCB; advisory board member or speakers’ bureau for AbbVie, Eli Lilly & Co., Janssen, Regeneron Pharmaceuticals, Inc., UCB. Andreas Wollenberg is an advisor, speaker, or investigator for ALK Abelló, Almirall, Anacor, Astellas, Beiersdorf AG, Bencard, Bioderma, Chugai, Eli Lilly & Co., Galderma, GSK, Hans Karrer, LEO Pharma, L’Oreal, Maruho, MedImmune, Novartis, Pfizer, Pierre Fabre, Sanofi, Regeneron Pharmaceuticals, Inc. Zhen Chen, John D. Davis, Abhijit Gadkari, Brad Shumel, Neil M.H. Graham, Marius Ardeleanu are employees and shareholders of Regeneron Pharmaceuticals, Inc. Meng Li, Laurent Eckert, Ana B. Rossi are employees of Sanofi, and may hold stock and/or stock options in the company. Ana B. Rossi ORCID: 0000-0001-5345-678X
- Brandt EB, Sivaprasad U. Th2 cytokines and atopic dermatitis. J Clin Cell Immunol. 2011;2(3):110.
- Gittler JK, Shemer A, Suárez-Fariñas M, et al. Progressive activation of T(H)2/ T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130:1344-1354.
- Wollenberg A, Oranje A, Deleuran M, et al. ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. J Eur Acad Dermatol Venereol. 2016;30;729-747.
- Silverberg JI, Garg NK, Paller AS, Fishbein AG, Zee PC. Sleep disturbances in adults with eczema are associated with impaired overall health: a US population-based study. J Invest Dermatol. 2015;135:56-66.
- Simpson EL, Bieber T, Eckert L, et al. Patient burden of moderate to severe atopic dermatitis (AD): insights from a phase 2b clinical trial of dupilumab in adults. J Am Acad Dermatol. 2016;74:491-498.
- Kaufman BP, Guttman-Yassky E, Alexis AF. Atopic dermatitis in diverse racial and ethnic groups -- variations in epidemiology, genetics, clinical presentation and treatment. Exp Dermatol. 2018;27:340-357.
- Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J Am Acad Dermatol. 2019;80:390-401.
- Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema prevalence in the United States: data from the 2003 National Survey of Children’s Health. J Invest Dermatol. 2011;131:67-73.
- Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71:116- 132.
- Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71:327- 349.
- Wollenberg A, Barbarot S, Bieber T, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatol Venereol. 2018;32:657-682.
- Macdonald LE, Karow M, Stevens S, et al. Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes. Proc Natl Acad Sci USA. 2014;111:5147-5152.
- Murphy AJ, Macdonald LE, Stevens S, et al. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proc Natl Acad Sci USA. 2014;111:5153-5158.
- US Food and Drug Administration. DUPIXENT® (dupilumab). Highlights of prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/ label/2019/761055s014lbl.pdf. Revised June 2019. Accessed July 25, 2019
- European Medicines Agency. DUPIXENT® (dupilumab). Summary of product characteristics. http://ec.europa.eu/health/documents/communityregister/ 2019/20190506144541/anx_144541_en.pdf. Accessed July 25, 2019.
- Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-highdose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388:31-44.
- Rabe K, Nair P, Brusselle G, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med. 2018;378:2475- 2485.
- Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378:2486- 2496.
- Beck LA, Thaçi D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130-139.
- Thaçi D, Simpson EL, Beck LA, et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016;387:40-52.
- Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375:2335-2348.
- Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389:2287- 2303.
- de Bruin-Weller M, Thaçi D, Smith CH, et al. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ). Br J Dermatol. 2018;178:1083-1101.
- Bachert C, Mannent L, Naclerio RM, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA. 2016;315:469-479.
- Hirano I, Dellon ES, Hamilton JD, et al. Dupilumab efficacy and safety in adult patients with active eosinophilic oesophagitis: a randomised doubleblind placebo-controlled phase 2 trial. United European Gastroenterol J. 2017;5:1138-1150.
- Davis JD, Bansal A, Hassman D, et al. Evaluation of potential diseasemediated drug-drug interaction in patients with moderate-to-severe atopic dermatitis receiving dupilumab. Clin Pharmacol Ther. 2018;104:1146-1154.
- Pellerin L, Henry J, Hsu CH, et al. Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin. J Allergy Clin Immunol. 2013;131:1094- 1102.
- Berdyshev E, Goleva E, Bronova I, et al. Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight. 2018;3:e98006.
- Taylor SC. Skin of color: biology, structure, function, and implications for dermatologic disease. J Am Acad Dermatol. 2002;46:S41-62.
- Bhattacharya T, Silverberg JI. Efficacy of systemic treatments for atopic dermatitis in racial and ethnic minorities in the United States. JAMA Dermatol. 2014;150:1232-1234.
- Eichenfield LF, Lucky AW, Langley RG, et al. Use of pimecrolimus cream 1% (Elidel) in the treatment of atopic dermatitis in infants and children: the effects of ethnic origin and baseline disease severity on treatment outcome. Int J Dermatol. 2005;44:70-75.
- Kim KH, Kono T. Overview of efficacy and safety of tacrolimus ointment in patients with atopic dermatitis in Asia and other areas. Int J Dermatol. 2011;50:1153-1161.