Effectiveness of antibacterial therapeutic clothing vs. nonantibacterial therapeutic clothing in patients with moderate-to-severe atopic dermatitis: a randomized controlled observer-blind pragmatic trial (ABC trial).

BACKGROUND: Increased Staphylococcus aureus (SA) colonization is considered an important factor in the pathogenesis of atopic dermatitis (AD). Antibacterial therapeutic clothing aims to reduce SA colonization and AD inflammation; however, its role in the management of AD remains poorly understood. OBJECTIVES: To investigate the effectiveness of antibacterial therapeutic clothing + standard topical treatment in patients with moderate-to-severe AD vs. standard therapeutic clothing + standard topical treatment; and, if effectiveness was demonstrated, to demonstrate its cost-effectiveness. METHODS: A pragmatic double-blinded multicentre randomized controlled trial (NCT04297215) was conducted in patients of all ages with moderate-to-severe AD. Patients were centrally randomized 1 : 1 : 1 to receive standard therapeutic clothing or antibacterial clothing based on chitosan or silver. The primary outcome was the between-group difference in Eczema Area and Severity Index (EASI) measured over 52 weeks. Secondary outcomes included patient-reported outcomes (PROs), topical corticosteroid (TCS) use, SA colonization, safety and cost-effectiveness. Outcomes were assessed by means of (generalized) linear mixed-model analyses. RESULTS: Between 16 March 2020 and 20 December 2021, 171 patients were enrolled. In total, 159 patients were included (54 in the standard therapeutic clothing group, 50 in the chitosan group and 55 in the silver group). Adherence was high [median 7 nights a week wear (interquartile range 3-7)]. Median EASI scores at baseline and at 4, 12, 26 and 52 weeks were 11.8, 4.3, 4.6, 4.2 and 3.6, respectively, in the standard therapeutic clothing group vs. 11.3, 5.0, 3.0, 3.0 and 4.4, respectively, in the chitosan group, and 11.6, 5.0, 5.4, 4.6 and 5.8, respectively, in the silver group. No differences in EASI over 52 weeks between the standard therapeutic clothing group, the chitosan group [-0.1, 95% confidence interval (CI) -0.3 to 0.2; P = 0.53] or the silver group (-0.1, 95% CI -0.3 to 0.2; P = 0.58) were found. However, a small significant group × time interaction effect between the standard and silver groups was found (P = 0.03), in which the silver group performed worse after 26 weeks. No differences between groups were found in PROs, TCS use, SA skin colonization and healthcare utilization. No severe adverse events or silver absorption were observed. CONCLUSIONS: The results of this study suggest no additional benefits of antibacterial agents in therapeutic clothing in patients with moderate-to-severe AD.

Dupilumab provides sustained effectiveness on patient-reported outcomes and favorable safety in patients with moderate-to-severe atopic dermatitis: Up to 5-year results from the daily practice BioDay registry.

BACKGROUND: Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. OBJECTIVE: To evaluate patient-reported outcome measures (PROMs) and the safety of dupilumab in patients with moderate-to-severe AD over a follow-up period of up to 5 years. METHODS: Data were extracted from the prospective, multicenter BioDay registry (October 2017-2022) of patients with moderate-to-severe AD treated with dupilumab in daily practice. RESULTS: In total 1223 patients, 1108 adults and 115 pediatric patients were included. After ≥1 year of treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8 and 8.7, 3.5 and 4.2, and 2.9 and 3.1 in adults, respectively, whilst these patient-reported outcome measures (PROMs) ranged between 8.9 and 10.9, 4.4 and 6.4, and 3.0 and 3.7 in pediatric patients, respectively. At follow-up, overall work impairment decreased from 40.1% to 16.3% to 13.3% in adults. Furthermore, class I obesity and itch-dominant patients generally had less favorable treatment response. Of all patients, 66.8% reported ≥1 adverse event, with conjunctivitis being the most common (33.7%). LIMITATIONS: The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. CONCLUSION: In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives.

Economic and Humanistic Burden in Paediatric Patients with Atopic Dermatitis.

Data concerning the economic and humanistic burden in patients with paediatric atopic dermatitis (AD) and their families are scarce. This retrospective study investigated these burdens in paediatric patients with AD using maintenance treatment with topical corticosteroids and/or conventional systemic immunosuppressants. Patient-reported outcomes regarding quality of life, AD severity, and parental work-related impairment were completed at inclusion. Data on healthcare resource utilization and medication prescription were collected retrospectively over the previous 12 months. Patients were categorized into mild, moderate or severe AD, based on Eczema Area and Severity Index score and medication use. Costs per patient per year per AD severity category were calculated. A total of 101 patients (median age 11.0 years (interquartile range 7.5-14.0), 47.5% men) were included, of whom 38 had mild AD, 37 moderate AD, and 26 severe AD. Mean ± standard deviation (SD) total costs patient per year for mild, moderate and severe AD were €1,812 ± €1,280, €2,680 ± €3,127, and €5,861 ± €3,993, respectively. Highest total direct and indirect costs were found in patients with severe AD, mainly due to higher healthcare and medication costs. Highest humanistic burden was found in patients with moderate AD. For example, the median (interquartile range) Patient-Oriented Eczema Measure score was significantly higher in these patients compared with mild and severe AD (19.0 (15.0-24.0) vs 12.0 (8.8-15.0) and 17.0 (9.5-22.0), respectively). AD in paediatric patients incurs considerable direct and indirect costs, especially in patients with severe AD. The high humanistic burden in patients with moderate AD underlines the need for effective and safe new treatment options for children with AD.

Identification of Risk Factors for Dupilumab-associated Ocular Surface Disease in Patients with Atopic Dermatitis.

This study identified risk factors for the development of dupilumab-associated ocular surface disease in patients with moderate-to-severe atopic dermatitis in a large prospective daily practice cohort. Data from the Dutch BioDay Registry were used to assess the risk of developing dupilumab-associated ocular surface disease, by performing univariate and multivariate logistic regression analyses. A total of 469 patients were included, of which 152/469 (32.4%) developed dupilumab-associated ocular surface disease. Multivariate analysis showed a statistically significant association of the development of dupilumab-associated ocular surface disease with a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at the start of dupilumab (odds ratio 5.16, 95% confidence interval 2.30-11.56, p < 0.001). In conclusion, a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at baseline was associated with the development of dupilumab-associated ocular surface disease in patients with atopic dermatitis.

Long-Term Effectiveness and Reasons for Discontinuation of Dupilumab in Patients With Atopic Dermatitis.

Importance: Limited data are available on the long-term effectiveness and safety of dupilumab for atopic dermatitis (AD) in daily practice. Objective: To evaluate clinical effectiveness and reasons for discontinuation of dupilumab treatment in children, adults, and older adults with AD with up to 5 years of treatment in daily practice. Design, Setting, and Participants: This prospective multicenter cohort study was conducted using the BioDay registry (4 academic and 10 nonacademic hospitals in the Netherlands) to identify patients with AD of all ages who were treated with dupilumab between October 2017 and December 2022. Main Outcomes and Measures: Clinical effectiveness was evaluated by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), and numeric rating scale (NRS) for pruritus, stratified by children (<18 years), adults (18-64 years), and older adults (≥65 years). In addition, time to response, treatment responders, EASI subscores, second treatment episodes, and thymus- and activation-related chemokine and eosinophil levels were assessed. For patients who discontinued dupilumab, the reason for discontinuation was evaluated. Results: In total, 1286 patients with AD (median [IQR] age, 38 [26-54] years; 726 [56.6%] male) were treated with dupilumab, including 130 children, 1025 adults, and 131 older adults. The median (IQR) follow-up time was 87.5 (32.0-157.0) weeks. Most patients maintained controlled AD, with EASI of 7 or lower and NRS for pruritus of 4 or lower varying between 78.6% and 92.3% and 72.2% and 88.2% for up to 5 years of treatment, respectively, while up to 70.5% of all patients prolonged the dosing interval to mostly 300 mg every 3 or 4 weeks. Mean EASI and NRS for pruritus were 2.7 (95% CI, 1.2-4.2) and 3.5 (95% CI, 2.7-4.3), respectively, after 5 years of treatment. Statistically significant differences between age groups were found over time for EASI and IGA; however, differences were rather small (week 52: EASI, 0.3-1.6; IGA, 0.12-0.26). No statistically significant differences between age groups were found for NRS for pruritus. Median thymus- and activation-related chemokine levels considerably decreased from 1751 pg/mL (95% CI, 1614-1900 pg/mL) to 390 pg/mL (95% CI, 368-413 pg/mL) after 6 months of treatment and remained low. Median eosinophil levels temporarily increased up to week 16, with a subsequently statistically significant decrease over time. In total, 306 patients (23.8%) discontinued dupilumab after a median (IQR) of 54.0 (29.0-110.00) weeks, with adverse events among 98 patients (7.6%) and ineffectiveness among 85 patients (6.6%) as the most frequently reported reasons. Forty-one patients (3.2%) restarted dupilumab, and most of these patients recaptured response. Conclusions and Relevance: In this cohort study with up to 5 years of follow-up, dupilumab maintained its clinical effectiveness, while two-thirds of patients tapered to a dosing interval of every 3 or 4 weeks. Treatment was discontinued in 23.8% of patients mainly due to adverse events and/or ineffectiveness.

Biologicals for pediatric patients with atopic dermatitis: practical challenges and knowledge gaps.

Biologicals are becoming increasingly important in the therapeutic landscape of pediatric patients with moderate-to-severe atopic dermatitis (AD). Currently, dupilumab and tralokinumab are registered for the treatment of moderate-to-severe AD, and novel biologicals are expected to follow. Dupilumab was the first biological registered for AD in pediatric patients and was recently approved for patients aged six months to five years. Current and emerging biologicals may address the unmet need for effective and safe treatment options for pediatric AD patients, however, little is known about the practical implementation of biologicals in infants and preschoolers (aged <6 years), including the timing of treatment initiation, discontinuation, and long-term administration of the subcutaneous injections. Currently, only a small number of biologicals are approved for the treatment of infants and preschoolers for other inflammatory diseases. Consequently, data on the practical implementation of biological treatment remain scarce. In addition, long-term effects, impact on co-morbidities, and impact on live-accentuated vaccination are still unknown. With the introduction of biologicals for AD from the age of six months, potential challenges within the implementation of biologicals may arise. Therefore, we aim to discuss current practical challenges and knowledge gaps of the treatment with biologicals in infants and preschoolers with AD.