Dupilumab provides rapid and sustained improvement in SCORAD outcomes in adults with moderate-to-severe atopic dermatitis: combined results of four randomized phase 3 trials

References

• Bieber T. Atopic dermatitis. Ann Dermatol. 2010;22(2):125–137.
   PubMed Web of Science ®Google Scholar
• Brunner PM, Silverberg JI, Guttman-Yassky E, et al. Increasing comorbidities suggest that atopic dermatitis is a systemic disorder. J Invest Dermatol. 2017;137(1):18–25.
   PubMed Web of Science ®Google Scholar
• Gittler JK, Shemer A, Suárez-Fariñas M, et al. Progressive activitation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130(6):1344–1354.
   PubMed Web of Science ®Google Scholar
• Goleva E, Berdyshev E, Leung DY. Epithelial barrier repair and prevention of allergy. J Clin Invest. 2019;129(4):1463–1474.
   PubMed Web of Science ®Google Scholar
• 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(5):729–747.
   PubMed Web of Science ®Google Scholar
• Sibbald C, Drucker AM. Patient burden of atopic dermatitis. Dermatol Clin. 2017;35(3):303–316.
   PubMed Web of Science ®Google Scholar
• 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(3):491–498.
   PubMed Web of Science ®Google Scholar
• Simpson EL, Guttman-Yassky E, Margolis DJ, et al. Association of inadequately controlled disease and disease severity with patient-reported disease burden in adults with atopic dermatitis. JAMA Dermatol. 2018;154(8):903–912.
   PubMed Web of Science ®Google Scholar
• Chiesa Fuxench ZC, Block JK, Boguniewicz M, et al. Atopic dermatitis in America study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the US adult population. J Invest Dermatol. 2019;139(3):583–590.
   PubMed Web of Science ®Google Scholar
• Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338–351.
   PubMed Web of Science ®Google Scholar
• Huet F, Faffa M-S, Poizeau F, et al. Characteristics of pruritus in relation to self-assessed severity of atopic dermatitis. Acta Derm Venerol. 2019;99(3):279–283.
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Gelfand JM, Margolis DJ, et al. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study. Ann Allergy Asthma Immunol. 2018;121(3):340–347.
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Gelfand JM, Margolis DJ, et al. Mental health burden and comorbidity in atopic dermatitis in US adults. Paper presented at: Annual Meeting of the American Academy of Dermatology; 2019 Mar 1–5; Washington, DC.
   Google Scholar
• Silverberg JI, Gelfand JM, Margolis DJ, et al. Symptoms and diagnosis of anxiety and depression in atopic dermatitis in U.S. adults. Br J Dermatol. 2019;181(3):554–565.
   PubMed Web of Science ®Google Scholar
• 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(2):390–401.
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Garg NK, Paller AS, et al. Sleep disturbances in adults with eczema are associated with impaired overall health: a US population-based study. J Invest Dermatol. 2015;135(1):56–66.
   PubMed Web of Science ®Google Scholar
• Schmitt J, Langan S, Deckert S, et al. Assessment of clinical signs of atopic dermatitis: a systematic review and recommendation. J Allergy Clin Immunol. 2013;132(6):1337–1347.
   PubMed Web of Science ®Google Scholar
• Charman CR, Venn AJ, Ravenscroft JC, et al. Translating Patient-Oriented Eczema Measure (POEM) scores into clinical practice by suggesting severity strata derived using anchor-based methods. Br J Dermatol. 2013;169(6):1326–1332.
   PubMed Web of Science ®Google Scholar
• Chopra R, Silverberg JI. Assessing the severity of atopic dermatitis in clinical trials and practice. Clin Dermatol. 2018;36(5):606–615.
   PubMed Web of Science ®Google Scholar
• Rehal B, Armstrong AW. Health outcome measures in atopic dermatitis: a systematic review of trends in disease severity and quality-of-life instruments 1985-2010. PLoS One. 2011;6(4):e17520.
   PubMed Web of Science ®Google Scholar
• Schmitt J, Spuls PI, Thomas KS, et al. The Harmonising Outcome Measures for Eczema (HOME) statement to assess clinical signs of atopic eczema in trials. J Allergy Clin Immunol. 2014;134(4):800–807.
   PubMed Web of Science ®Google Scholar
• European Task Force on Atopic Dermatitis. Severity scoring of atopic dermatitis: the SCORAD index. Consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186:23–31.
   PubMed Web of Science ®Google Scholar
• Kunz B, Oranje AP, Labrèze L, et al. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1997;195(1):10–19.
   PubMed Web of Science ®Google Scholar
• 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(5):657–682.
   PubMed Web of Science ®Google Scholar
• Oranje AP, Glazenburg EJ, Wolkerstorfer A, et al. Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score. Br J Dermatol. 2007;157(4):645–648.
   PubMed Web of Science ®Google Scholar
• Chopra R, Vakharia PP, Sacotte R, et al. Severity strata for Eczema Area and Severity Index (EASI), modified EASI, Scoring Atopic Dermatitis (SCORAD), objective SCORAD, Atopic Dermatitis Severity Index and body surface area in adolescents and adults with atopic dermatitis. Br J Dermatol. 2017;177(5):1316–1321.
   PubMed Web of Science ®Google Scholar
• Wollenberg A, Barbarot S, Bieber T, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II. J Eur Acad Dermatol Venereol. 2018;32(6):850–878.
   PubMed Web of Science ®Google Scholar
• Chopra R, Vakharia PP, Sacotte R, et al. Relationship between EASI and SCORAD severity assessments for atopic dermatitis. J Allergy Clin Immunol. 2017;140(6):1708–1710.
   PubMed Web of Science ®Google Scholar
• 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(14):5147–5152.
   PubMed Web of Science ®Google Scholar
• 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(14):5153–5158.
   PubMed Web of Science ®Google Scholar
• US Food and Drug Administration [Internet]. Silver Spring (MD): FDA. DUPIXENT® (dupilumab). Highlights of prescribing information; 2017 [cited 2019 September 26]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761055s014lbl.pdf
   Google Scholar
• European Medicines Agency [internet]. London (UK): EMA. DUPIXENT® (dupilumab). Summary of product characteristics; [cited 2019 September 26]; Available from: https://ec.europa.eu/health/documents/community-register/2019/20190801145601/anx_145601_en.pdf
   Google Scholar
• 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(24):2335–2348.
   PubMed Web of Science ®Google Scholar
• 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(5):1083–1101.
   PubMed Web of Science ®Google Scholar
• 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(10086):2287–2303.
   PubMed Web of Science ®Google Scholar
• Schram ME, Spuls PI, Leeflang MM, et al. EASI, (objective) SCORAD and POEM for atopic eczema: responsiveness and minimal clinically important difference. Allergy. 2012;67(1):99–106.
   PubMed Web of Science ®Google Scholar
• Reich A, Heisig M, Phan NQ, et al. Visual analogue scale: evaluation of the instrument for the assessment of pruritus. Acta Derm Venerol. 2012;92(5):497–501.
   PubMed Web of Science ®Google Scholar
• Akinlade B, Guttman-Yassky E, de Bruin-Weller M, et al. Conjunctivitis in dupilumab clinical trials. Br J Dermatol. 2019;181(3):459–473.
   PubMed Web of Science ®Google Scholar
• Eichenfield LF, Bieber T, Beck LA, et al. Infections in dupilumab clinical trials in atopic dermatitis: a comprehensive pooled analysis. Am J Clin Dermatol. 2019;20(3):443–456.
   PubMed Web of Science ®Google Scholar
• Wollenberg A, Beck LA, Blauvelt A, et al. Laboratory safety of dupilumab in moderate‐to‐severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). Br J Dermatol. 2019. [Epub ahead of print]. Accessed April 27, 2020.
   Web of Science ®Google Scholar
• Vakharia PP, Chopra R, Sacotte R, et al. Validation of patient-reported global severity of atopic dermatitis in adults. Allergy. 2018;73(2):451–458.
   PubMed Web of Science ®Google Scholar
• Stalder JF, Barbarot S, Wollenberg A, et al. Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe. Allergy. 2011;66(8):1114–1121.
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Gelfand JM, Margolis DJ, et al. Severity strata for POEM, PO-SCORAD, and DLQI in US adults with atopic dermatitis. Ann Allergy Asthma Immunol. 2018;121(4):464–471.
   PubMed Web of Science ®Google Scholar
• Cork MJ, Eckert L, Simpson EL, et al. Dupilumab improves patient-reported symptoms of atopic dermatitis, symptoms of anxiety and depression, and health-related quality of life in moderate-to-severe atopic dermatitis: analysis of pooled data from the randomized trials SOLO 1 and SOLO 2. J Dermatolog Treat. 2019. [Epub ahead of print]. Accessed April 27, 2020.
   Web of Science ®Google Scholar
• Silverberg JI, Eckert L, Yosipovitch G, et al. Dupilumab treatment results in rapid and sustained improvements in itch in adults with moderate-to-severe atopic dermatitis. Paper presented at: 77th Annual Meeting of the Society for Investigative Dermatology; 2019. May 8–11; Chicago, IL.
   Google Scholar
• Yosipovitch G, Reaney M, Mastey V, et al. Peak Pruritus Numerical Rating Scale: psychometric validation and responder definition for assessing itch in moderate‐to‐severe atopic dermatitis. Br J Dermatol. 2019;181(4):761–769.
   PubMed Web of Science ®Google Scholar
• Brandt EB, Sivaprasad U. Th2 cytokines and atopic dermatitis. J Clin Cell Immunol. 2011;2:110.
   PubMedGoogle Scholar
• Bhogal RK, Bona CA. Regulatory effect of extracellular signal-regulated kinases (ERK) on type I collagen synthesis in human dermal fibroblasts stimulated by IL-4 and IL-13. Int Rev Immunol. 2008;27(6):472–496.
   PubMed Web of Science ®Google Scholar