JAMA Dermatology

<jats:p>This case report describes a child with lesions that initially appeared as vesicles and progressively spread in a centrifugal pattern, forming concentric, spiraled rings.</jats:p>

Bullous cutaneous lesion on the hand of an adolescent.

Enferm Infecc Microbiol Clin

Report of the first case of tinea corporis bullosa by Trichophyton tonsurans.

Hautarzt

Tinea pseudoimbricata: a narrative literature review and five new cases.

Wien Med Wochenschr

This case report describes a child with lesions that initially appeared as vesicles and progressively spread in a centrifugal pattern, forming concentric, spiraled rings.

Bullous Tinea Manuum.

Bullous Tinea Manuum

Pediatric Dermatology

<jats:title>ABSTRACT</jats:title><jats:p>Atopic dermatitis (<jats:sc>AD</jats:sc>) is a common and burdensome disease. Treatment options for pediatric and adolescent patients (&lt; 18 years old) with moderate‐to‐severe <jats:sc>AD</jats:sc> are limited, and real‐world data on disease burden are lacking. This study examined patient‐reported disease burden and treatments in pediatric and adolescent patients to identify opportunities for patient benefit. Data were drawn from the Adelphi Real World Pediatric <jats:sc>AD</jats:sc> Disease Specific Programme (DSP), a cross‐sectional survey of physicians and patients &lt; 18 years old, conducted in Europe and the United States between February–June 2019. Physicians documented demographics, clinical characteristics, and treatment history. Patients and/or their caregivers described disease burden, the degree of symptomatic bother, and quality of life (QoL). Data from 772 patients with moderate–to‐severe <jats:sc>AD</jats:sc> were analyzed (pediatric; <jats:italic>n</jats:italic> = 393, 0–11 years, adolescent; <jats:italic>n</jats:italic> = 379, 12–17 years). Adolescents were more likely to be receiving a systemic corticosteroid (24% vs. 12%), phototherapy (15% vs. 6%), systemic immunosuppressant (15% vs. 6%) or a biologic treatment (5% vs. 1%) than pediatric patients (<jats:italic>p</jats:italic> &lt; 0.0001). Two‐thirds of patients had a high degree of “bother” from itch, and 38% reporting itch as the “most bothersome” symptom. More adolescent patients reported “bother” related to anxiety than pediatric patients (67% vs. 49%, <jats:italic>p</jats:italic> &lt; 0.0001). Adolescent patients reported a significantly higher burden of embarrassment/self‐consciousness (<jats:italic>p</jats:italic> &lt; 0.0001) and <jats:sc>AD</jats:sc> impact on friendships (<jats:italic>p</jats:italic> &lt; 0.05). Disease burden differed between pediatric and adolescent patients with <jats:sc>AD</jats:sc>. Treatment considerations for pediatric and adolescent patients with <jats:sc>AD</jats:sc> should take into account these factors, with future research directed toward improving the QoL in these patients.</jats:p>

publication_history

received

accepted

published

Eli Lilly and Company

Atopic dermatitis (AD) is a common and burdensome disease. Treatment options for pediatric and adolescent patients (< 18 years old) with moderate-to-severe AD are limited, and real-world data on disease burden are lacking. This study examined patient-reported disease burden and treatments in pediatric and adolescent patients to identify opportunities for patient benefit. Data were drawn from the Adelphi Real World Pediatric AD Disease Specific Programme (DSP), a cross-sectional survey of physicians and patients < 18 years old, conducted in Europe and the United States between February-June 2019. Physicians documented demographics, clinical characteristics, and treatment history. Patients and/or their caregivers described disease burden, the degree of symptomatic bother, and quality of life (QoL). Data from 772 patients with moderate-to-severe AD were analyzed (pediatric; n = 393, 0-11 years, adolescent; n = 379, 12-17 years). Adolescents were more likely to be receiving a systemic corticosteroid (24% vs. 12%), phototherapy (15% vs. 6%), systemic immunosuppressant (15% vs. 6%) or a biologic treatment (5% vs. 1%) than pediatric patients (p < 0.0001). Two-thirds of patients had a high degree of "bother" from itch, and 38% reporting itch as the "most bothersome" symptom. More adolescent patients reported "bother" related to anxiety than pediatric patients (67% vs. 49%, p < 0.0001). Adolescent patients reported a significantly higher burden of embarrassment/self-consciousness (p < 0.0001) and AD impact on friendships (p < 0.05). Disease burden differed between pediatric and adolescent patients with AD. Treatment considerations for pediatric and adolescent patients with AD should take into account these factors, with future research directed toward improving the QoL in these patients.

Patient-Reported Impact of Atopic Dermatitis on Pediatric and Adolescent Patients With Moderate-To-Severe Disease: Results of a Real-World, Cross-Sectional Survey.

Patient‐Reported Impact of Atopic Dermatitis on Pediatric and Adolescent Patients With Moderate‐To‐Severe Disease: Results of a Real‐World, Cross‐Sectional Survey

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background/Objectives</jats:title><jats:p>Efficacy and safety of roflumilast cream 0.15% were demonstrated in patients aged ≥ 6 years with atopic dermatitis (AD) in two Phase 3 trials. This Phase 3 parallel‐group, double‐blind trial (INTEGUMENT‐PED; NCT04845620) compared the efficacy and safety of roflumilast cream 0.05% and a vehicle in patients aged 2–5 years with AD.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients aged 2–5 years with mild‐to‐moderate AD were treated with once‐daily roflumilast cream 0.05% or vehicle for 4 weeks. The primary efficacy endpoint was Validated Investigator Global Assessment for AD (vIGA‐AD) Success (0 [Clear] or 1 [Almost Clear] plus ≥ 2‐grade improvement from baseline) at Week 4. Other endpoints included ≥ 75% improvement in Eczema Area and Severity Index (EASI‐75) and Worst Itch‐Numeric Rating Score (WI‐NRS) Success (≥ 4‐point improvement in patients with baseline ≥ 4). Safety and tolerability were also assessed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Among 437 and 215 patients treated with roflumilast and vehicle, respectively, significantly greater proportions of the roflumilast group achieved Week‐4 vIGA‐AD Success (25.4% vs. 10.7%; <jats:italic>p</jats:italic> &lt; 0.0001), EASI‐75 (39.4% vs. 20.6%; <jats:italic>p</jats:italic> &lt; 0.0001), and WI‐NRS Success (35.3% vs. 18.0%; nominal <jats:italic>p</jats:italic> = 0.0002). Improvement in pruritus was observed within 24 h after the first application (nominal <jats:italic>p</jats:italic> = 0.0014). Treatment‐emergent adverse event (TEAE) rates were low in both groups, and 98.9% were mild or moderate. At all timepoints, stinging/burning that caused definite discomfort was reported by ≤ 0.7% of caregivers of patients in the roflumilast group.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In this Phase 3 trial, once‐daily roflumilast cream 0.05% improved AD signs/symptoms in patients aged 2–5 years, with early pruritus improvement, low AE rates, and local tolerability comparable with vehicle.</jats:p><jats:p>
<jats:bold>Trial Registration:</jats:bold> <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://clinicaltrials.gov">ClinicalTrials.gov</jats:ext-link>: NCT04845620</jats:p></jats:sec>

Long‐Term Safety and Effectiveness With Roflumilast Cream 0.15% in Patients ≥ 6 Years of Age With Atopic Dermatitis: A Phase 3 Open‐Label Extension Trial

Dermatitis

Efficacy and safety of roflumilast cream 0.15% were demonstrated in patients aged ≥ 6 years with atopic dermatitis (AD) in two Phase 3 trials. This Phase 3 parallel-group, double-blind trial (INTEGUMENT-PED; NCT04845620) compared the efficacy and safety of roflumilast cream 0.05% and a vehicle in patients aged 2-5 years with AD.
Patients aged 2-5 years with mild-to-moderate AD were treated with once-daily roflumilast cream 0.05% or vehicle for 4 weeks. The primary efficacy endpoint was Validated Investigator Global Assessment for AD (vIGA-AD) Success (0 [Clear] or 1 [Almost Clear] plus ≥ 2-grade improvement from baseline) at Week 4. Other endpoints included ≥ 75% improvement in Eczema Area and Severity Index (EASI-75) and Worst Itch-Numeric Rating Score (WI-NRS) Success (≥ 4-point improvement in patients with baseline ≥ 4). Safety and tolerability were also assessed.
Among 437 and 215 patients treated with roflumilast and vehicle, respectively, significantly greater proportions of the roflumilast group achieved Week-4 vIGA-AD Success (25.4% vs. 10.7%; p < 0.0001), EASI-75 (39.4% vs. 20.6%; p < 0.0001), and WI-NRS Success (35.3% vs. 18.0%; nominal p = 0.0002). Improvement in pruritus was observed within 24 h after the first application (nominal p = 0.0014). Treatment-emergent adverse event (TEAE) rates were low in both groups, and 98.9% were mild or moderate. At all timepoints, stinging/burning that caused definite discomfort was reported by ≤ 0.7% of caregivers of patients in the roflumilast group.
In this Phase 3 trial, once-daily roflumilast cream 0.05% improved AD signs/symptoms in patients aged 2-5 years, with early pruritus improvement, low AE rates, and local tolerability comparable with vehicle.
ClinicalTrials.gov: NCT04845620.

Efficacy and Safety of Once-Daily Roflumilast Cream 0.05% in Pediatric Patients Aged 2-5 Years With Mild-to-Moderate Atopic Dermatitis (INTEGUMENT-PED): A Phase 3 Randomized Controlled Trial.

Efficacy and Safety of Once‐Daily Roflumilast Cream 0.05% in Pediatric Patients Aged 2–5 Years With Mild‐to‐Moderate Atopic Dermatitis (<scp>INTEGUMENT</scp>‐<scp>PED</scp>): A Phase 3 Randomized Controlled Trial

<jats:sec id="ab-doi240027-4"><jats:title>Importance</jats:title><jats:p>Limited data are available on the long-term effectiveness and safety of dupilumab for atopic dermatitis (AD) in daily practice.</jats:p></jats:sec><jats:sec id="ab-doi240027-5"><jats:title>Objective</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-doi240027-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-doi240027-7"><jats:title>Main Outcomes and Measures</jats:title><jats:p>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 (&amp;amp;lt;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.</jats:p></jats:sec><jats:sec id="ab-doi240027-8"><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-doi240027-9"><jats:title>Conclusions and Relevance</jats:title><jats:p>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.</jats:p></jats:sec>

Dupilumab shows long-term effectiveness in a large cohort of treatment-refractory atopic dermatitis patients in daily practice: 52-week results from the Dutch BioDay registry.

J Am Acad Dermatol

Dupilumab maintains long-term disease control in adults with moderate-to-severe atopic dermatitis as measured by well-controlled weeks: results from the LIBERTY AD CHRONOS clinical trial.

Dermatol Ther (Heidelb)

Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study.

A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: ineffectiveness in head-and-neck dermatitis.

J Eur Acad Dermatol Venereol

Longer dupilumab dosing intervals in adult patients with atopic dermatitis: experience from a French multicentre retrospective cohort study.

Br J Dermatol

Patient-centered dupilumab dosing regimen leads to successful dose reduction in persistently controlled atopic dermatitis.

Allergy

Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis: a retrospective analysis.

Dermatol Ther

Successful tapering of dupilumab in patients with atopic dermatitis with low disease activity: a large pragmatic daily practice study from the BioDay registry.

Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: a randomized clinical trial.

JAMA Dermatol

Two-year efficacy, safety, and drug survival of dupilumab for atopic dermatitis: a real-world Canadian multicenter retrospective study.

JAAD Int

104-week safety and effectiveness of dupilumab in the treatment of severe atopic dermatitis: the experience of 5 reference dermatology units in Spain.

An Bras Dermatol

Dupilumab for the treatment of atopic dermatitis: real-world data from the Czech Republic BIOREP registry.

J Dermatolog Treat

Dupilumab provides acceptable safety and sustained efficacy for up to 4 years in an open-label study of adults with moderate-to-severe atopic dermatitis.

Am J Clin Dermatol

What the Eczema Area and Severity Index score tells us about the severity of atopic dermatitis: an interpretability study.

A systematic review of Investigator Global Assessment (IGA) in atopic dermatitis (AD) trials: many options, no standards.

Assessment of pruritus intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus.

Acta Derm Venereol

Treat-to-target in atopic dermatitis: an international consensus on a set of core decision points for systemic therapies.

Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial.

Lancet

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management.

Expert Rev Respir Med

Biomarkers for atopic dermatitis: a systematic review and meta-analysis.

Curr Opin Allergy Clin Immunol

Real-life effectiveness and safety of dupilumab in adolescents with atopic dermatitis: a 52-week single-center retrospective study.

Dupilumab improves clinical scores in children and adolescents with moderate to severe atopic dermatitis: a real-world, single-center study.

J Allergy Clin Immunol Pract

A 52-week update of a multicentre Italian real-world experience on effectiveness and safety of dupilumab in adolescents with moderate-to-severe atopic dermatitis.

Effect of dupilumab on blood eosinophil counts in patients with asthma, chronic rhinosinusitis with nasal polyps, atopic dermatitis, or eosinophilic esophagitis.

Dupilumab therapy of atopic dermatitis of the elderly: a multicentre, real-life study.

Dupilumab with topical corticosteroids provides rapid and sustained improvement in adults with moderate-to-severe atopic dermatitis across anatomic regions over 52 weeks.

Dupilumab demonstrates rapid and consistent improvement in extent and signs of atopic dermatitis across all anatomical regions in pediatric patients 6 years of age and older.

Facial and neck erythema associated with dupilumab treatment: a systematic review.

Reasons for discontinuation of dupilumab in adult atopic dermatitis in clinical practice.

Evaluation of long-term efficacy, safety, and reasons for discontinuation of dupilumab for moderate to severe atopic dermatitis in clinical practice: a retrospective cohort study.

Long-term drug survival of dupilumab and associated predictors in moderate-to-severe atopic dermatitis: a real-world prospective cohort study.

Global, regional, and national cancer incidence and death for 29 cancer groups in 2019 and trends analysis of the global cancer burden, 1990-2019.

J Hematol Oncol

Limited data are available on the long-term effectiveness and safety of dupilumab for atopic dermatitis (AD) in daily practice.
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.
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.
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.
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.
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.

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

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

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