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      Real-world outcomes of children treated with dupilumab for moderate-to-severe atopic dermatitis: a single-centre retrospective observational UK study

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      Clinical and Experimental Dermatology
      Oxford University Press (OUP)

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          Abstract

          Background

          Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged ≥ 6 months.

          Objectives

          The aim of this study was to examine real-world outcomes and safety of dupilumab in British children with moderate-to-severe AD attending a tertiary referral paediatric centre.

          Methods

          Skin and quality of life scores, adverse events and discontinuation rates were assessed. Patients aged ≤ 18 years with moderate-to-severe AD were included if they had skin scores recorded at baseline and at least one follow-up visit. Efficacy and safety were assessed using descriptive statistics.

          Results

          In this retrospective observational survey, 72 children/teenagers, with a median age of 14 years (range 7–18) were included. Oral systemic immunosuppressants had failed to control AD in 88% of children recruited. All patients commenced on dupilumab had pretreatment eczema skin scores consistent with moderate-to-severe disease, with a median Eczema Area and Severity Index (EASI) score of 25 [interquartile range (IQR) 20–31]. EASI scores decreased by a median of 94% (IQR 82–100) and remained consistently low over 10–52 months of the study, with a median EASI score at final follow-up of 2 (IQR 0–6). Of the 72 children, 8 (11%) were able to discontinue dupilumab as they were in remission. Nineteen (26%) experienced adverse events, most commonly conjunctivitis (12 patients; 17%). Eight (11%) discontinued dupilumab (six with ongoing inflammatory skin flares, one with severe allergic conjunctivitis, one with intercurrent Wilson disease).

          Conclusions

          Dupilumab was highly effective in treating most children with moderate-to-severe AD with good safety outcomes in the real world. However, 10% of children may need alternative therapy because of drug ineffectiveness or side-effects.

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          Most cited references19

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          Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis : A Phase 3 Randomized Clinical Trial

          Question What is the efficacy and safety of dupilumab monotherapy in adolescents with moderate to severe inadequately controlled atopic dermatitis? Findings In this randomized phase 3 clinical trial including 251 adolescents with moderate to severe atopic dermatitis, dupilumab 200 or 300 mg every 2 weeks and 300 mg every 4 weeks resulted in a significant treatment response vs placebo following 16-week treatment, with an acceptable safety profile. Meaning The findings appear to support the use of dupilumab for the treatment of adolescents with moderate to severe atopic dermatitis. Importance Adolescents with atopic dermatitis (AD) have high disease burden negatively affecting quality of life, with limited treatment options. The efficacy and safety of dupilumab, a monoclonal antibody, approved for treatment in adolescent patients with inadequately controlled AD, remain unknown in this patient population. Objective To assess the efficacy and safety of dupilumab monotherapy in adolescents with moderate to severe inadequately controlled AD. Design, Setting, and Participants A randomized, double-blind, parallel-group, phase 3 clinical trial was conducted at 45 US and Canadian centers between March 21, 2017, and June 5, 2018. A total of 251 adolescents with moderate to severe AD inadequately controlled by topical medications or for whom topical therapy was inadvisable were included. Interventions Patients were randomized (1:1:1; interactive-response system; stratified by severity and body weight) to 16-week treatment with dupilumab, 200 mg (n = 43; baseline weight <60 kg), or dupilumab, 300 mg (n = 39; baseline weight ≥60 kg), every 2 weeks; dupilumab, 300 mg, every 4 weeks (n = 84); or placebo (n = 85). Main Outcomes and Measures Proportion of patients with 75% or more improvement from baseline in Eczema Area and Severity Index (EASI-75) (scores range from 0 to 72, with higher scores indicating greater severity) and Investigator’s Global Assessment (IGA) 0 or 1 on a 5-point scale (scores range from 0 to 4, with higher scores indicating greater severity) at week 16. Results A total of 251 patients were randomized (mean [SD] age, 14.5 [1.7] years; 148 [59.0%] male). Of 250 patients with data available on concurrent allergic conditions, most had comorbid type 2 diseases (asthma, 134 [53.6%]; food allergies, 60.8%; allergic rhinitis, 65.6%). A total of 240 patients (95.6%) completed the study. Dupilumab achieved both coprimary end points at week 16. The proportion of patients with EASI-75 improvement from baseline increased (every 2 weeks, 41.5%; every 4 weeks, 38.1%; placebo, 8.2%) with differences vs placebo of 33.2% (95% CI, 21.1%-45.4%) for every 2 weeks and 29.9% (95% CI, 17.9%-41.8%) for every 4 weeks ( P  < .001). Efficacy of the every-2-week regimen was generally superior to the every-4-week regimen. Patients in the dupilumab arms had higher percentage values of conjunctivitis (every 2 weeks, 9.8%; every 4 weeks, 10.8%; placebo, 4.7%) and injection-site reactions (every 2 weeks, 8.5%; every 4 weeks, 6.0%; placebo, 3.5%), and lower nonherpetic skin infections (every 2 weeks, 9.8%; every 4 weeks, 9.6%; placebo, 18.8%). Conclusions and Relevance In this study, dupilumab significantly improved AD signs, symptoms, and quality of life in adolescents with moderate to severe AD, with an acceptable safety profile. Placebo-corrected efficacy and safety of dupilumab were similar in adolescents and adults. Trial Registration ClinicalTrials.gov identifier: NCT03054428 This phase 3 randomized clinical trial evaluates the efficacy and safety of 2 dose regimens of dupilumab for treatment of moderate to severe atopic dermatitis in adolescents.
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            Prevalence and Incidence of Atopic Dermatitis: A Systematic Review

            The primary objective of this study was to systematically review and analyse epidemiological studies of the prevalence and incidence of atopic dermatitis (AD) during childhood and adulthood, focusing on data from the 21 st century. A systematic search of PubMed, EMBASE and Google (manual search) was performed in June 2019, followed by data abstraction and study quality assessment (Newcastle–Ottawa Scale). Cross-sectional and longitudinal epidemiological studies of individuals with AD (doctor-diagnosed or standardized definition) were included. Of 7,207 references reviewed, 378 moderate/good-quality studies were included: 352 on prevalence of AD and 26 on incidence of AD. In the 21 st century, the 1-year prevalence of doctor-diagnosed AD ranged from 1.2% in Asia to 17.1% in Europe in adults, and 0.96% to 22.6% in children in Asia. The 1-year incidence ranged from 10.2 (95% confidence interval (95% CI) 9.9– 10.6) in Italy to 95.6 (95% CI 93.4–97.9) per 1,000 person-years in children in Scotland. There were few recent studies on incidence of AD in the 21 st century and no studies on adults only; most studies were conducted in Europe and the USA. Epidemiological studies on childhood and adulthood AD in different continents are still needed, especially on the incidence of AD during adulthood.
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              Quality of life and childhood atopic dermatitis: the misery of living with childhood eczema.

              The misery of living with atopic eczema (syn. dermatitis, AD) cannot be overstated for it may have a profoundly negative effect on the health-related quality of life (HRQoL) of children and their family unit in many cases. As it is one of the commonest chronic relapsing childhood dermatosis (UK lifetime prevalence 16-20% by 20 years), with increasing worldwide prevalence, this has major social and financial implications for individuals, healthcare providers and society as a whole. This review explores the impact of AD on the lives of children and their family units and the use of some of the recently developed HRQoL measures, which have enabled investigation and categorisation of the physical, psychological and psycho-social effects of childhood eczema across all aspects of life. These effects include symptoms of itching and soreness, which cause sleeplessness in over 60%. Sleep deprivation leads to tiredness, mood changes and impaired psychosocial functioning of the child and family, particularly at school and work. Embarrassment, comments, teasing and bullying frequently cause social isolation and may lead to depression or school avoidance. The child's lifestyle is often limited, particularly in respect to clothing, holidays, staying with friends, owning pets, swimming or the ability to play or do sports. Restriction of normal family life, difficulties with complicated treatment regimes and increased work in caring for a child with eczema lead to parental exhaustion and feelings of hopelessness, guilt, anger and depression. The hidden costs involved in eczema management can be significant and have particular impact on lower income families. The impairment of quality of life caused by childhood eczema has been shown to be greater than or equal to other common childhood diseases such as asthma and diabetes, emphasising the importance of eczema as a major chronic childhood disease. HRQoL measures are proving to be valuable tools for use in the clinical setting, as outcome measures for pharmaceutical studies, for health economics and audit purposes. It is therefore recommended that in future, they should be used in conjunction with objective measures of severity, as part of the assessment process of a child with atopic eczema. Lack of information on eczema and treatments heightens parental anxiety. Education of all individuals involved in the care of children with eczema is fundamental in the management of AD and it is essential to provide simple clear, unambiguous information on treatment and disease management in order to reduce the negative impact on HRQoL.
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                Author and article information

                Journal
                Clinical and Experimental Dermatology
                Oxford University Press (OUP)
                0307-6938
                1365-2230
                June 2024
                May 21 2024
                January 08 2024
                June 2024
                May 21 2024
                January 08 2024
                : 49
                : 6
                : 578-583
                Article
                10.1093/ced/llae013
                343acca4-b14e-4704-a105-4600234f1da5
                © 2024

                https://creativecommons.org/licenses/by-nc/4.0/

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