Dupilumab in daily practice for the treatment of pediatric atopic dermatitis: 28‐week clinical and biomarker results from the BioDay registry

Abstract

Background: Dupilumab has proven to be an effective and safe treatment for atopic dermatitis (AD) in pediatric patients in clinical trials. However, few daily practice studies are available. The aim of this study is to evaluate the effect of 28 weeks dupilumab treatment on effectiveness, safety, and serum biomarkers in pediatric patients with moderate-to-severe AD in daily practice. Methods: Patients visited the outpatient clinic at baseline, 4, 16, and 28 weeks of treatment. Disease severity was assessed by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Numeric Rating Scale (NRS)-pruritus and -pain, and the Patient-Oriented Eczema Measure (POEM). Side effects were evaluated. Nineteen severity-associated serum biomarkers were measured. Predicted-EASI (p-EASI) was calculated.Results: Sixty-one patients were included. Respectively 75.4%, 49.2%, and 24.6% reached clear. Improvement of ≥4 points on POEM, NRS-pruritus, and NRS-pain was reached by 84.7%, 45.3%, and 77.4%, respectively. Most reported side effects were conjunctivitis (n = 10) and headache (n = 4). Biomarkers TARC, PARC, periostin, sIL-2Ra, and eotaxin-3 significantly decreased during treatment. The p-EASI showed a significant correlation with disease severity. Conclusion:Dupilumab treatment significantly improved disease severity and diseaseassociated symptoms and decreased severity-associated serum biomarkers in pediatric AD patients in daily practice.

Multicenter Canadian case series of pediatric patients less than 12 years of age with moderate‐to‐severe atopic dermatitis treated with dupilumab

“…EASI‐75 was achieved by 75% of patients in both Napolitano's and our studies, but our patients more often achieved EASI‐90 (71% in our study vs. 9% in theirs) 9 . Another multicenter cohort study reported EASI‐75 being achieved by 43% and EASI‐90 being achieved by 16% of patients at week 16 11 …”

“…Compared to other case series, 7–11 our patients had experienced more difficult‐to‐treat AD based on the number of previous systemic therapies (Tables 1 and 2); however, similar EASI improvements were achieved. In another case series, patients received systemic corticosteroids (44%), cyclosporine (25%), and methotrexate (7%) 9 while, in our cohort, more patients received methotrexate (45%) and fewer patients received systemic corticosteroids (35%) and cyclosporine (18%).…”

“…9 Another multicenter cohort study reported EASI-75 being achieved by 43% and EASI-90 being achieved by 16% of patients at week 16. 11 In our cohort, mean IGA decreased from 3. reflecting a more severe and complex AD population. As noted previously, reported delays to medication access are likely a severe underestimate of true delays experienced by patients as the study selected for patients who were ultimately able to access dupilumab.…”

Itch: from the skin to the brain – peripheral and central neural sensitization in chronic itch

“…The role of the pruritogen periostin in peripheral neural sensitization has been recently reported. Increased periostin levels have been found in chronic itchy skin conditions such as AD, PN, and bullous pemphigoid, and positively correlated with itch severity ( Ariëns et al, 2020 ; Hashimoto et al, 2021 ; Kamphuis et al, 2022 ; Sans-de San Nicolàs et al, 2023 ). Periostin is an intracellular matrix protein thought to be produced by epidermal keratinocytes and dermal fibroblasts, and binds to its receptor integrin α V β3, causing immune cells to release itch cytokines IL-4, IL-13, IL-31 and inducing sensory nerve fiber sensitization by direct activation of integrin alpha B receptor ( Masuoka et al, 2012 ; Hashimoto and Yosipovitch, 2019 ; Izuhara et al, 2019 ; Mishra et al, 2020 ).…”

Understanding the Medical Dictionary for Regulatory Activities for Assessing Safety in Atopic Dermatitis Clinical Trials

“…Although a highly effective and safe drug, dupilumab is associated with conjunctivitis. 2 In AD clinical trials, rates of conjunctivitis vary, which may be due to the different MedDRA codes that can capture conjunctivitis-related events. We analyzed recent AD clinical trials to illustrate how an understanding of MedDRA may be helpful when interpreting the rate of conjunctivitis observed with dupilumab treatment and the safety of drugs more generally.…”