Dupilumab Provides Rapid and Sustained Clinically Meaningful Responses in Adults with Moderate-to-severe Atopic Dermatitis

Jonathan I. Silverberg1, Eric L. Simpson2, Mark Boguniewicz3,4, Marjolein S. De Bruin-Weller5, Peter Foley6, Yoko Kataoka7, Gaëlle Bégo-Le Bagousse8, Zhen Chen9, Brad Shumel9, Jingdong Chao9 and Ana B. Rossi10

1George Washington University School of Medicine of Health Sciences, Washington, DC, 2Oregon Health and Science University, Portland, OR, 3National Jewish Health, 4University of Colorado School of Medicine, Denver, CO, USA, 5National Expertise Center of Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands, 6The University of Melbourne, Skin & Cancer Foundation, Inc., Carlton, VIC, Australia, 7Department of Dermatology, Osaka Habikino Medical Center, Osaka, Japan, 8Sanofi, Chilly-Mazarin, France, 9Regeneron Pharmaceuticals, Inc., Tarrytown, NY and 10Sanofi Genzyme, Cambridge, MA, USA

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.

Key words: atopic dermatitis; treat-to-target; responder; Eczema Area and Severity Index; pruritus; Dermatology Life Quality Index.

Accepted Oct 7, 2021; Epub ahead of print Oct 7, 2021

Acta Derm Venereol 2021; 101: adv00585.

doi: 10.2340/actadv.v101.307

Corr: Jonathan I. Silverberg, George Washington University School of Medicine of Health Sciences, Ross Hall, 300 Eye Street NW, Washington 20037, DC, USA. E-mail: jonathanisilverberg@gmail.com


In accordance with an international consensus, this study estimated the proportion of responders to dupilumab through a multidimensional composite endpoint assessing atopic dermatitis signs, symptoms (pruritus), and quality of life in a 1-year phase 3 trial of dupilumab with concomitant topical corticosteroids in adults with moderate-to-severe atopic dermatitis. Most dupilumab-treated patients (64%) achieved improvement equivalent to minimal disease in ≥1 atopic dermatitis domain after the first dose, and 84% were responders at 4 months. This response was sustained over 1 year. This comprehensive view of the efficacy of dupilumab from the perspective of both patients and physicians might provide better guidance to clinicians in daily practice.


The ultimate goal in the management of moderate-to-severe atopic dermatitis (AD), for both physicians and patients, is to achieve disease control. The Harmonizing Outcome Measures for Eczema initiative recommends a multidimensional assessment that includes clinician-reported signs, patient-reported symptoms, quality of life (QoL), and long-term control (1); a recommendation recently supported by the European Task Force on Atopic Dermatitis (ETFAD) (2).

Currently, there is no single tool available to assess all salient aspects of AD and treatment responses (Table I). Eczema Area and Severity Index (EASI) ≤ 7.0 (10) and objective SCORing Atopic Dermatitis (o-SCORAD) < 24 are interpreted as mild disease activity (11, 12). Itch can be measured using the Peak Pruritus Numerical Rating Scale (NRS). A score ≤ 4 indicates mild or no pruritus (13) and a change of ≥ 2 to 4 points from baseline is the threshold for defining a clinically relevant (within- person) response in Peak Pruritus NRS (6, 14). The Patient-Oriented Eczema Measure (POEM) (7) assesses patient-reported disease activity over the previous week, with a value ≤ 7 considered mild AD (4). QoL can be assessed by the dermatological disease-specific Dermatology Life Quality Index (DLQI), with values ≤ 5 consistent with a small or no effect on patient’s health-related QoL (13, 15) and a change of ≥ 4 points from baseline defined as clinically relevant (8, 9).

Dupilumab is a fully human VelocImmune®-derived monoclonal antibody (16, 17), which blocks the shared receptor component for interleukin (IL)-4 and IL-13, thus inhibiting signalling of both IL-4 and IL-13, which are key and central drivers of type 2 inflammatory diseases, such as AD, asthma, allergic rhinitis, and food allergies (18). Dupilumab is a targeted, systemic, non-immunosuppressant treatment with a favorable benefit/risk profile, appropriate for long-term management of AD, as shown by prevention of AD flares in 85% of patients and providing well-controlled disease in > 85% of weeks in patients treated for 1 year (19, 20). The safety of dupilumab has been evaluated in patients treated for up to 3 years (21), during which time there was no need for routine laboratory monitoring (22), and in children aged 6–11 years with severe AD (23). Real-world evidence shows high persistence of treatment with dupilumab, with 91% and 88% of patients continuing treatment after 1 and 2 years, respectively (24).

The ETFAD states that multidimensional assessment is important for identification of relevant treatment targets (2), and an international consensus, through an eDelphi process, recently published a treat-to-target framework guidance for systemic treatment in adults with moderate-to-severe AD (25). To better characterize the multidimensional benefits of dupilumab treatment in AD over time, post hoc analyses were performed on data from a randomized, placebo-controlled, double-blind, 1-year phase 3 trial (LIBERTY AD CHRONOS (NCT02260986)) to assess the proportion of patients achieving short-term clinically meaningful improvement, as well as the proportion achieving no or mild/minimal disease, based on signs, symptoms, and QoL at 6 months and 1 year. This study also evaluated the percentage of patients with improvement in all 3 domains of AD (signs, symptoms, and QoL) in response to dupilumab treatment.


Study design

The study design, patient populations, and efficacy and safety results for LIBERTY AD CHRONOS have been reported previously (26). Briefly, a total of 740 patients were randomized (1:3:3) to receive 300 mg every 2 weeks (q2w, n = 106), dupilumab 300 mg weekly (qw, n = 319), or placebo for 52 weeks (n = 315). All patients received concomitant medium-potency topical corticosteroids (TCS) or low-potency TCS for areas where continued treatment with medium-potency TCS is not recommended. The study design allowed for tapering of TCS after clearance of AD skin lesions and TCS reinstitution if lesions recurred, which would reflect real-world use of TCS (26). Eligible patients had moderate-to-severe AD with inadequate response to topical treatment, baseline EASI ≥ 16, Investigator’s Global Assessment (IGA) scores of 3 or 4 (moderate or severe), and body surface area affected by AD ≥ 10%.

The trial was conducted in accordance with the principles of the Declaration of Helsinki. All patients provided signed written informed consent before performing any study procedures. Institutional review boards and independent ethics committees reviewed and approved the protocol, informed consent form, and patient information before study initiation.


Consistent with the ETFAD (2) and an international consensus discussion on treatment targets (25), 2 composite endpoints were defined for an initial acceptable target of “clinically meaningful response” at week 16 (4, 6, 14, 27) and an optimal treatment target of “no or mild/minimal disease” at 6 months and 1 year (6, 27, 28), as follows: