Dupilumab Provides Rapid and Sustained Clinically Meaningful Responses in Adults with Moderate-to-severe Atopic Dermatitis
Keywords:atopic dermatitis, treat-to-target, responder, Eczema Area and Severity Index, pruritus, Dermatology Life Quality Index
Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a real-world setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo- controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis.
Leshem YA, Chalmers JR, Apfelbacher C, Furue M, Gerbens LAA, Prinsen CAC, et al. Measuring atopic eczema symptoms in clinical practice: the first consensus statement from the Harmonising Outcome Measures for Eczema in clinical practice initiative. J Am Acad Dermatol 2020; 82: 1181-1186.
Thyssen JP, Vestergaard C, Deleuran M, de Bruin-Weller MS, Bieber T, Taieb A, et al. European Task Force on Atopic Dermatitis (ETFAD): treatment targets and treatable traits in atopic dermatitis. J Eur Acad Dermatol Venereol 2020; 34: e839-e842.
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: e17520.
Schram ME, Spuls PI, Leeflang MMG, Lindeboom R, Bos JD, Schmitt J. EASI, (objective) SCORAD and POEM for atopic eczema: responsiveness and minimal clinically important difference. Allergy 2012; 67: 99-106.
Stalder JF, Taïeb A, Atherton DJ, Bieber P, Bonifazi E, Broberg A, et al. Severity scoring of atopic dermatitis: the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology 1993; 186: 23-31.
Yosipovitch G, Reaney M, Mastey V, Eckert L, Abbé A, Nelson L, 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: 761-769.
Charman CR, Venn AJ, Williams HC. The patient-oriented eczema measure: development and initial validation of a new tool for measuring atopic eczema severity from the patients' perspective. Arch Dermatol 2004; 140: 1513-1519.
Basra MK, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology 2015; 230: 27-33.
Badia X, Mascaró JM, Lozano R. Measuring health-related quality of life in patients with mild to moderate eczema and psoriasis: clinical validity, reliability and sensitivity to change of the DLQI. The Cavide Research Group. Br J Dermatol 1999; 141: 698-702.
Leshem YA, Hajar T, Hanifin JM, Simpson EL. What the Eczema Area and Severity Index score tells us about the severity of atopic dermatitis: an interpretability study. Br J Dermatol 2015; 172: 1353-1357.
Barbarot S, Wollenberg A, Silverberg JI, Deleuran M, Pellacani G, Armario-Hita JC, et al. 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. J Dermatolog Treat 2020 Jun 8 [Online ahead of print].
Chopra R, Vakharia PP, Sacotte R, Patel N, Immaneni S, White T, 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: 1316-1321.
Vakharia PP, Chopra R, Sacotte R, Patel N, Immaneni S, White T, et al. Severity strata for five patient-reported outcomes in adults with atopic dermatitis. Br J Dermatol 2018; 178: 925-930.
Silverberg JI, Lei D, Yousaf M, Janmohamed SR, Vakharia PP, Chopra R, et al. What are the best endpoints for Eczema Area and Severity Index and Scoring Atopic Dermatitis in clinical practice? A prospective observational study. Br J Dermatol 2021; 184: 888-895.
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) - a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19: 210-216.
Macdonald LE, Karow M, Stevens S, Auerbach W, Poueymirou WT, Yasenchak J, et al. Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes. Proc Natl Acad Sci U S A 2014; 111: 5147-5152.
Murphy AJ, Macdonald LE, Stevens S, Karow M, Dore AT, Pobursky K, et al. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proc Natl Acad Sci U S A 2014; 111: 5153-5158.
Gandhi N, Bennett BL, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov 2016; 15: 35-50.
Merola JF, Sidbury R, Wollenberg A, Chen Z, Zhang A, Shumel B, et al. Dupilumab prevents flares in adults with moderate-to-severe atopic dermatitis in a 52-week randomized controlled phase 3 trial. J Am Acad Dermatol 2020; 84: 495-497.
Wu JJ, Spelman L, Tan JL, Etoh T, Zhang H, Shumel B, et al. Dupilumab maintains long-term disease control in adults with moderate-to-severe atopic dermatitis as measured by well-controlled weeks: results from the LIBERTY AD CHRONOS clinical trial. Dermatol Ther (Heidelb) 2021; 11: 327-330.
Deleuran M, Thaçi D, Beck LA, de Bruin-Weller M, Blauvelt A, Forman S, et al. Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study. J Am Acad Dermatol 2020; 82: 377-388.
Wollenberg A, Beck LA, Blauvelt A, Simpson EL, Chen Z, Chen Q, 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 2020; 182: 1120-1135.
Paller AS, Siegfried EC, Thaçi D, Wollenberg A, Cork MJ, Arkwright PD, et al. 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. J Am Acad Dermatol 2020; 83: 1282-1293.
Spekhorst LS, Ariëns LFM, van der Schaft J, Bakker DS, Kamsteeg M, Oosting AJ, et al. Two-year drug survival of dupilumab in a large cohort of difficult-to-treat adult atopic dermatitis patients compared to cyclosporine A and methotrexate: results from the BioDay registry. Allergy 2020; 75: 2376-2379.
de Bruin-Weller M, Biedermann T, Bissonnette R, Deleuran M, Foley P, Girolomoni G, et al. Treat-to-target in atopic dermatitis: an international consensus on a set of core decision points for systemic therapies. Acta Derm Venereol 2021; 101: adv00402.
Blauvelt A, de Bruin-Weller M, Gooderham M, Cather JC, Weisman J, Pariser D, 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.
Basra MKA, Fenech R, Gatt RM, Salek MS, Finlay AY. The Dermatology Life Quality Index 1994-2007: a comprehensive review of validation data and clinical results. Br J Dermatol 2008; 159: 997-1035.
Regeneron Pharmaceuticals. DUPIXENT® (dupilumab) [Prescribing Information]. [accessed February 17, 2021] Available from: https://www.regeneron.com/sites/default/files/Dupixent_FPI.pdf.
Simpson EL, de Bruin-Weller M, Flohr C, Ardern-Jones MR, Barbarot S, Deleuran M, et al. When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council. J Am Acad Dermatol 2017; 77: 623-633.
Silverberg JI, Simpson EL, Ardeleanu M, Thaçi D, Barbarot S, Bagel J, et al. Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment: a pooled analysis of data from two phase III trials. Br J Dermatol 2019; 181: 80-87.
Paller AS, Bansal A, Simpson EL, Boguniewicz M, Blauvelt A, Siegfried EC, et al. Clinically meaningful responses to dupilumab in adolescents with uncontrolled moderate‑to‑severe atopic dermatitis: post‑hoc analyses from a randomized clinical trial. Am J Clin Dermatol 2020; 21: 119-131.
Ariens LFM, van der Schaft J, Spekhorst LS, Bakker DS, Romeijn GLE, Kouwenhoven TA, et al. Dupilumab shows long-term effectiveness in a large cohort of treatment-refractory atopic dermatitis patients in daily practice: 52-weeks results from the Dutch BioDay registry. J Am Acad Dermatol 2021; 84: 1000-1009.
Nettis E, Ferrucci SM, Ortoncelly M, Pellacani G, Foti C, Di Leo E, et al. Use of dupilumab for 543 adult patients with moderate-to-severe atopic dermatitis: a multicenter, retrospective study. J Investig Allergol Clin Immunol 2020; Aug 26 [Online ahead of print].
Halling AS, Loft N, Silverberg JI, Guttman-Yassky E, Thyssen JP. Real-world evidence of dupilumab efficacy and risk of adverse events: a systematic review and meta-analysis. J Am Acad Dermatol 2021; 84: 139-147.
How to Cite
Copyright (c) 2021 Jonathan I. Silverberg, Eric L. Simpson, Mark Boguniewicz, Marjolein S. De Bruin-Weller, Peter Foley, Yoko Kataoka, Gaëlle Bégo-Le-Bagousse, Zhen Chen, Brad Shumel, Jingdong Chao, Ana B. Rossi
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.