Children with severe atopic dermatitis (AD) have a multidimensional disease burden characterized by skin lesions over large body surface areas (BSAs), pruritus, sleep deprivation, symptoms of anxiety and depression, and impact on quality of life.1-4 A recent worldwide survey reported a prevalence of 12.2% of diagnosed AD in children aged 6 to 11 years, with 36.2% and 9.1% of these children having moderate or severe disease, respectively.5 Dupilumab, a fully human monoclonal antibody,6,7 blocks the shared receptor subunit for IL-4 and IL-13, thus inhibiting signaling of these key and central inflammatory cytokines in AD pathophysiology. As of June 2020, dupilumab is approved by the FDA for the treatment of patients aged 6 years and older with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.8,9 A randomized, double-blind, controlled study of dupilumab (NCT03345914),10 in which children aged 6 to 11 years were treated for 16 weeks with dupilumab and topical corticosteroids (TCS), demonstrated statistically significant, clinically meaningful, and rapid improvements in AD signs and symptoms, including itch, anxiety, depression, sleep, and quality of life, in children treated with dupilumab plus TCS compared with TCS only.
Here we present selected photographic case studies from that trial, which are characteristic of patients with a response to dupilumab, as a visual demonstration of the treatment effect that cannot be adequately conveyed by text alone.
LIBERTY AD PEDS was a randomized, double-blind, placebo-controlled, phase 3 trial enrolling 367 children aged 6 to 11 years with severe AD inadequately controlled by topical therapies. Patients were randomized 1:1:1 to placebo, dupilumab 300 mg every 4 weeks (q4w), or dupilumab every 2 weeks (q2w; 100 mg if baseline body weight was <30 kg or 200 mg if baseline weight was ≥30 kg) for 16 weeks. All patients received concomitant TCS. Here we report 12 patients treated with dupilumab in this study, with images before and after 16 weeks of dupilumab treatment, as well as results on several key outcome measures characterizing AD severity, including Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), percent BSA affected by AD, Peak Pruritus Numerical Rating Scale (NRS), SCORAD visual analog scale (VAS) itch, SCORAD VAS sleep loss, Patient-Oriented Eczema Measure (POEM), and Children’s Dermatology Life Quality Index (CDLQI).
Pruritus, an important symptom of AD, was evaluated by two different assessments: Peak Pruritus NRS and SCORAD VAS itch. Both are 10-point scales of pruritus severity; however, for the Peak Pruritus NRS, patients are asked: “On a scale of 0–10, what was the worst level of itch during the last 24 hours?”11 The SCORAD VAS itch asked patients: “What was the average itch in the last 3 days?”
Individual cases include images that correspond to the case at baseline (top left image) and after 16 weeks of treatment (top right image). The rainbow graphics in the figures display change in absolute values from baseline (red circles) to week 16 (blue circles) for each outcome. Similarly, the rainbow colors represent established severity strata validated for EASI,12 SCORAD,12 Peak Pruritus NRS,11,13 POEM,14 and CDLQI.15 The rainbow graphics for BSA, pruritus VAS, and sleep loss VAS in all figures do not show distinct color bands, as specific severity strata have not been validated for these outcomes. The spider graphics show percent reduction in each outcome; lines closer to the outer edge of the spider plot represent greater improvement from baseline.
Case 1. Patient 1 was a 7-year-old boy weighing 20.3 kg with AD diagnosed at age 1 year. He had a personal history of keratoconjunctivitis, allergic rhinitis, asthma, and allergies to sulfa antibiotics, dust mites, and pollen. His AD was uncontrolled despite previous treatment with TCS, systemic corticosteroids, and cyclosporine. After 16 weeks of treatment with dupilumab 300 mg q4w, significant improvements were seen in AD signs (IGA, EASI, BSA, SCORAD) and patient-assessed symptoms (itch, POEM; Figure 1).
Case 2. Patient 2 was a 6-year-old boy weighing 19.9 kg who developed AD at age 1 year. The patient also had a personal history of asthma and allergic rhinitis. Previous treatments for AD included hydroxyzine, topical triamcinolone, hydrocortisone, and tacrolimus, as well as the systemic immunosuppressant cyclosporin. However, the patient reported more than 20 flares of AD in the previous year (flares defined as worsening of AD necessitating treatment escalation). Following treatment with dupilumab 300 mg q4w, signs and symptoms were assessed as mild, with almost complete improvement in sleep loss and quality of life. Before and after photos show improvement in perioral edema/papulation (Figure 2).
Case 3. Patient 3 was a 7-year-old boy weighing 21.3 kg who had AD for most of his life. In addition to a history of use of several TCS (desonide, mometasone, triamcinolone, clobetasol) and systemic prednisolone for treatment of AD, the patient was also receiving medication for moderate persistent asthma and seasonal allergic rhinitis. His caregiver also reported a personal history of keratoconjunctivitis. The patient was randomized to 16 weeks of dupilumab 300 mg q4w that led to 100% improvement in IGA, EASI, and BSA scores, a high improvement in quality of life as assessed by CDLQI, and some minor improvements in itch (Figure 3).
Case 4. Patient 4 was a 6-year-old girl weighing 22.3 kg at study baseline who developed AD at the age of 2 years. Prior treatment for AD included topical hydrocortisone, desonide, mometasone, hydrocortisone butyrate, and triamcinolone. The patient also had asthma, seasonal allergic rhinitis, and keratoconjunctivitis. The study treatment consisted of dupilumab 300 mg q4w and led to a decrease in IGA score from severe (4) to moderate (3), as well as a 60% to 80% improvement in signs as assessed by EASI, SCORAD, and affected BSA. The 16-week study regimen also led to considerable improvement in quality of life (CDLQI) and almost 100% improvement from baseline in pruritus and sleep loss. Before and after photos clearly show improvement in excoriations (Figure 4).
Case 5. Patient 5 was a 10-year-old girl weighing 36.7 kg who had AD for most of her life and had 14 flares in the year prior to the study. Prior and concomitant medications for AD included topical hydrocortisone, triamcinolone acetonide, and crisaborole. The patient also had comorbid asthma and allergic rhinitis. Treatment with dupilumab 300 mg q4w for 16 weeks led to a decrease of IGA score from severe (4) to almost clear (1), as well as nearly 80% improvement in EASI and percent BSA affected. Some improvements were also seen in measures of pruritus. Clear improvement in lichenification was observed (Figure 5).