Signs Of Atopic Dermatitis Research Articles

Evaluation of the Efficacy of an Ecobiological Dermo-Cosmetic Product to Help Manage and Prevent Relapses of Eyelid Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic relapsing, inflammatory disease which causes eczematous lesions. Itching and symptoms visibility can have a significant impact on quality of life. This is the case when eyelids are affected. Therefore, we evaluated a dermo-cosmetic product designed to care AD on eyelids. An initial analysis of the product included 20 healthy women with no AD signs. A clinical evaluation of the effect of the product on AD sign severity was performed on 33 subjects presenting AD symptoms on eyelids. We also analyzed the product's capacity to prevent relapses in a parallel group clinical evaluation performed on 66 subjects. First, on the forearm skin of healthy subjects, the product reduces erythema and decreases transepidermal water loss when used for 28 days. Second, when clinically evaluated on subjects with eyelid symptoms undergoing a corticoid treatment, the product leads to reduced AD signs scored by a dermatologist, better self-evaluation of symptoms by subjects, and improved quality of life. Besides, upon assessment in a randomized controlled clinical evaluation with subjects prone to AD relapses but without symptoms, the product also drastically reduces relapse frequency. If erythema reduction is the only sign identified by a dermatologist, the product greatly and rapidly improves the quality of life of subjects. These effects can be explained by the known actions of the product's ingredients. Rich in hydrating compounds, fatty acids and anti-inflammatory compounds, it aims at maintaining and restoring the epidermis structure and function to preserve it from irritants. It effectively shows that a daily care and hygiene routine with a dermo-cosmetic product designed according to an ecobiological approach leads to objective improvement of AD and subjective perception of quality of life.

Stratum corneum lipid and cytokine biomarkers at age 2 months predict the future onset of atopic dermatitis

Atopic dermatitis (AD) commonly occurs in children and can progress into severe phenotypes or atopic march, causing significant impairment in quality of life. It is important to find early biomarkers of future onset of AD before any clinical manifestations. We sought to find early predictors of future onset of AD in skin stratum corneum (SC). Skin tape strips were collected from the forearm of newborns (n= 111) with and without family history of atopic diseases at the age of 2 months before any signs of clinical AD. Children were clinically monitored until they reached age 2 years to ensure the presence or absence of AD. Skin tape strips were subjected to lipidomic analyses by the liquid chromatography electrospray ionization tandem mass spectrometry and cytokine determination by Meso Scale Discovery U-Plex assay. Overall, 22 of 74 (29.7%) and 5 of 37 (13.5%) infants developed AD in the risk group and the control group, respectively. In the SC of future AD children, protein-bound ceramides were decreased (P< .001), whereas unsaturated sphingomyelin species (P< .0001) and "short-chain" nonhydroxy fatty acid sphingosine and alpha-hydroxy fatty acid sphingosine ceramides were elevated (P< .01 and .05, respectively) as compared with healthy children. Thymic stromal lymphopoietin and IL-13 levels were increased in the SC of future AD subjects (by 74.5% and 78.3%, P= .0022 and P< .0001, respectively). Multivariable logistic regression analysis revealed strong AD predicting power of the combination of family history, type 2 cytokines, and dysregulated lipids, with an odds ratio reaching 54.0 (95% CI, 9.2-317.5). Noninvasive skin tape strip analysis at age 2 months can identify asymptomatic children at risk of future AD development with a high probability.

Efficacy and Safety of Dupilumab Maintained in Adults ≥ 60 Years of Age with Moderate-to-Severe Atopic Dermatitis: Analysis of Pooled Data from Four Randomized Clinical Trials.

Adults aged ≥ 60 years are often underrepresented in atopic dermatitis (AD) clinical trials; age-related comorbidities may impact treatment efficacy and safety. The aim was to report dupilumab efficacy and safety in patients aged ≥ 60 years with moderate-to-severe AD. Data were pooled from four randomized, placebo-controlled dupilumab trials of patients with moderate-to-severe AD (LIBERTY AD SOLO 1 and 2, LIBERTY AD CAFÉ, and LIBERTY AD CHRONOS) and stratified by age (<60 [N = 2261] and ≥ 60 [N = 183] years). Patients received dupilumab 300 mg every week (qw) or every 2 weeks (q2w), or placebo with/without topical corticosteroids. Post hoc efficacy at week 16 was examined using broad categorical and continuous assessments of skin lesions, symptoms, biomarkers, and quality of life. Safety was also assessed. In the ≥ 60-year-old group at week 16, a greater proportion of dupilumab-treated patients achieved an Investigator's Global Assessment score of 0/1 (q2w: 44.4%; qw: 39.7%) and 75% improvement in Eczema Area and Severity Index (63.0%; 61.6%) versus placebo (7.1% and 14.3%, respectively; P < 0.0001). Type 2 inflammation biomarkers (immunoglobulin E and thymus and activation-regulated chemokine) were also significantly reduced in dupilumab- versus placebo-treated patients (P < 0.01). Results were similar in the < 60-year-old group. The exposure-adjusted incidences of adverse events in dupilumab-treated patients were generally similar to those receiving placebo, with numerically fewer treatment-emergent adverse events in the dupilumab-treated ≥ 60-year-old group versus placebo. There were fewer patients in the ≥ 60-year-old group; post hoc analyses. Dupilumab improved AD signs and symptoms in patients aged ≥ 60 years; results were comparable to those in patients aged <60 years. Safety was consistent with the known dupilumab safety profile. ClinicalTrials.gov: NCT02277743, NCT02277769, NCT02755649, NCT02260986. Does dupilumab benefit adults aged 60 years and older with moderate-to-severe atopic dermatitis?(MP4 20,787 KB).

Efficacy and Safety of Dupilumab in Patients With Erythrodermic Atopic Dermatitis

Erythrodermic atopic dermatitis (AD) is a severe AD subtype defined by extensive skin involvement, leading to complications and sometimes hospitalization. To assess dupilumab's efficacy and safety in patients with erythrodermic AD in clinical trials. This post hoc analysis included patients enrolled in 6 multicenter, multinational, randomized, double-blind, placebo-controlled trials. Patients included in this analysis met erythrodermic AD criteria of 90% or greater body surface area (BSA) affected by AD and Global Individual Sign Score for erythema of 1 or higher. Data analyses for this post hoc analysis were conducted between March 5, 2019, and October 24, 2020. Dupilumab once weekly or every 2 weeks, or placebo, either as monotherapy or with concomitant topical corticosteroids (TCS). Efficacy (BSA, Eczema Area and Severity Index [EASI] score, Peak Pruritus Numerical Rating Scale [PP-NRS] score), changes in serum biomarkers (thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase), and safety (incidence of adverse events) at week 16. Data were pooled within each regimen; monotherapy and concomitant TCS results are shown separately. Of 3075 randomized patients, 209 met criteria for erythrodermic AD at baseline, with the median age being 31 and 39 years in the monotherapy and concomitant TCS trials, respectively, similar to the overall populations (34 and 36 years, respectively); 71.3% (n = 97) and 74.0% (n = 54) of patients, respectively, were male (compared with 58.7% and 60.6% in the overall populations). In patients with erythrodermic AD, dupilumab once weekly and every 2 weeks vs placebo significantly improved percentage of BSA affected by AD (least squares mean percent change [SE]) with monotherapy (-42.0% [7.7%] and -39.9% [6.5%] vs -17.2% [11.0%]; P = .03) and concomitant TCS (-63.2% [6.7%] and -56.1% [9.1%] vs -14.5% [7.3%]; P < .001); EASI score with monotherapy (-58.5% [9.0%] and -58.3% [7.9%] vs -22.3% [12.4%]; P = .004 and P = .003, respectively) and concomitant TCS (-78.9% [7.8%] and -70.6% [10.1%] vs 19.3% [8.2%]; P < .001); and PP-NRS score in monotherapy (-45.9% [7.8%] and -33.9% [6.6%] vs -0.6% [9.4%]; P < .001) and concomitant therapy (-53.0% [8.1%] and -55.7% [10.8%] vs -26.0% [8.8%]; P = .006 and P = .01, respectively). Nominally statistically significant improvement was seen as early as week 1 (EASI and PP-NRS scores with monotherapy). Biomarker levels were significantly reduced vs placebo. The most frequent adverse events in dupilumab-treated patients were injection-site reaction, conjunctivitis, and nasopharyngitis. In this post hoc analysis of 6 randomized clinical trials, treatment with dupilumab resulted in rapid, sustained improvements in AD signs and symptoms with acceptable safety in patients with erythrodermic AD, similar to those in the trials' overall patient population. ClinicalTrials.gov Identifiers: NCT01859988, NCT02277743, NCT02277769, NCT03054428, NCT02260986, NCT02755649.

336 Efficacy of dupilumab in infants and preschoolers with atopic dermatitis up to 1 year

Abstract Continuous use of several traditional systemic atopic dermatitis (AD) treatments in pediatric patients is not recommended due to safety concerns and lack of long-term efficacy data. Children aged 6 months to 5 years with moderate-to-severe AD who had participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434, part B; parent study) were enrolled in an open-label extension (OLE) study (NCT02612454). Patients received subcutaneous dupilumab every 4 weeks (200 mg for children weighing 5 to &amp;lt;15 kg; 300 mg for 15 to &amp;lt;30 kg). Topical AD treatments were allowed. Relative to the parent study baseline, mean percentage changes (± standard error) in Eczema Area and Severity Index score were −41.6 (±4.6) and −54.0 (±3.2) at OLE baseline, −74.5 (±3.7) and −81.7 (±1.8) at week 16, and −85.6 (±3.5) and −86.4 (±2.2) at week 52 in the 200 and 300 mg dupilumab groups, respectively. The number of patients (%) achieving an Investigator’s Global Assessment score of 0/1 increased from OLE baseline (6/61 [9.8%] and 15/116 [12.9%]) to week 16 (22/58 [37.9%] and 35/115 [30.4%]), and at week 52 (16/34 [47.1%] and 18/54 [33.3%]) in the 200 and 300 mg dupilumab groups, respectively. The overall safety of dupilumab treatment administered for up to 1 year was consistent with the known dupilumab safety profile. Dupilumab treatment for 1 year provides sustained improvement in signs of AD in patients aged 6 months to 5 years with moderate-to-severe AD.

308 Tralokinumab provides other clinically meaningful improvements in adolescents with moderate-to-severe atopic dermatitis who did not achieve IGA 0/1 at week 16

Abstract In the monotherapy phase 3 trial (ECZTRA 6, NCT03526861) in adolescents with moderate-to-severe atopic dermatitis (AD) treated with tralokinumab, IGA of clear/almost clear skin (IGA 0/1) at week 16 was a primary endpoint. IGA 0/1 can be a high standard to achieve for patients with moderate-to-severe AD and may not fully reflect achievement of other clinically meaningful parameters, such as improvement in signs, symptoms and/or quality-of-life (QoL). To assess the impact of tralokinumab (150 or 300 mg) vs. placebo on other clinically meaningful parameters at week 16 in the subset of patients who did not achieve IGA 0/1 at week 16 and/or used rescue medication. Adolescents (12–17 years) were randomized to subcutaneous tralokinumab 150 or 300 mg, or placebo, every 2 weeks. Patients who did not achieve IGA 0/1 at week 16 and/or utilized rescue therapy were included in this post-hoc analysis. Non-responder imputation was used for patients who utilized rescue therapy or had missing data. Clinically meaningful responses were defined as EASI-50, ≥ 3-point improvement in pruritus NRS, or ≥6-point improvement in CDLQI. At week 16, 78.6% and 82.5% of tralokinumab-treated patients (150 mg/300 mg) vs. 95.7% (placebo) exhibited IGA &amp;gt; 1 and/or used rescue therapy. 36.4% (150 mg) and 52.5% (300 mg) of patients with IGA &amp;gt; 1 in the tralokinumab arms, compared to 21.1% (placebo), achieved clinically meaningful responses in at least one measure: EASI-50, pruritus NRS, or CDLQI. Greater proportions of tralokinumab-treated patients (150/300 mg vs. placebo) achieved EASI-50 (31.2%/41.3% vs. 10.0%) and ≥3-point improvement in pruritus NRS (21.6%/22.8% vs. 8.0%). A greater proportion of tralokinumab 300 mg patients vs. placebo (35.2% vs. 15.0%) achieved ≥6-point improvement in CDLQI. Many tralokinumab-treated adolescents who did not achieve IGA 0/1 at week 16 and/or used rescue therapy still achieved clinically meaningful improvements in AD signs, symptoms, and/or QoL.

329 Efficacy and safety of dupilumab treatment with concomitant topical corticosteroids in children aged 6 months to 5 years with severe atopic dermatitis

Abstract There are limited approved systemic treatment options for children with atopic dermatitis (AD). Dupilumab is now approved in the United States for patients 6 months and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies. European Medicines Agency is evaluating the use of dupilumab in children aged 6 months through 5 years with severe AD only. To report the efficacy and safety of dupilumab in the subgroup of children aged 6 months to 5 years with severe AD (IGA score = 4) at baseline in the LIBERTY AD PRESCHOOL trial (NCT03346434 part B). Patients aged 6 months to 5 years with inadequately controlled moderate-to-severe AD were enrolled in LIBERTY AD PRESCHOOL (part B), a randomized, double-blind placebo-controlled phase 3 study. Patients were randomized to either dupilumab 200/300 mg every 4 weeks (200 mg if baseline weight 5 to &amp;lt;15 kg, 300 mg if 15 to &amp;lt;30 kg) or placebo for 16 weeks. All patients initiated standardized treatment with low-potency topical corticosteroids (TCS) from day –14. This analysis reports efficacy and quality-of-life endpoints including a 75% reduction from baseline in the Eczema Area and Severity Index (EASI-75), Peak-Pruritus Numerical Rating Scale (PP-NRS), Children’s Dermatology Life Quality Index (CDLQI, for children aged 4 to &amp;lt;6 years), and Infant’s Dermatitis Quality Of Life (IDQOL, for children &amp;lt;4 years) in children with severe AD. Of the total trial population of 162 patients with moderate-to-severe AD, 125 patients with severe AD at baseline were randomized: 63 to the dupilumab + TCS treatment group and 62 to the placebo + TCS treatment group. Baseline demographics were similar. Mean (SD) baseline disease characteristics were also similar between the dupilumab and placebo groups: EASI (38.8 [13.7] vs. 35.4 [12]), body surface area (63.1% [21] vs. 58.9% [21.4]), weekly average PP-NRS (7.6 [1.4] vs. 7.6 [1.6]), CDLQI (17.5 [5.5] vs. 17.8 [6.4]) and IDQOL (18.4 [5.1] vs. 17.4 [5.4]). Dupilumab treatment resulted in a rapid and significant increase in the proportion of patients achieving EASI-75 compared with placebo treatment by week 4 (27% vs. 4.8%; P = 0.0009). By week 16, this improvement was further increased compared with the placebo group (46% vs. 7%; P &amp;lt; 0.0001). At week 16, dupilumab-treated patients had a significantly greater percent reduction from baseline in PP-NRS compared with the placebo group (LS mean (SE)–41.8 [5.4] vs. 0.5 [5.4]; P &amp;lt; 0.0001). Dupilumab also resulted in significant improvement in quality-of-life outcomes compared with placebo (LS mean [SE]) change from baseline to week 16 in CDLQI (−9.1 [1.1] vs. −2.6 [1.2]; P &amp;lt; 0.0001); IDQOL (−9.1 [1.3] vs. −0.6 [1.1]; P &amp;lt; 0.0001). Treatment-emergent adverse events (TEAEs) were reported in 42 (66.7%) patients in the dupilumab group and 45 (73.8%) patients in the placebo group. Most TEAEs were mild to moderate and deemed unrelated to the study drug by the investigator. The most common TEAE was atopic dermatitis in both the dupilumab group (10 [15.9%]) and placebo group (16 [26.2%]). Additionally, TEAEs in the conjunctivitis cluster were reported by 4 (6.4%) patients in the dupilumab group and none in the placebo group. In the placebo group, 3 (4.9%) serious adverse events were reported. No dupilumab-related adverse events were serious or led to treatment discontinuation. Dupilumab significantly improved AD signs, symptoms, and quality of life in children aged 6 months to 5 years with severe AD. The safety profile was consistent with that previously seen in adults, adolescents, and children aged &amp;gt; 6 years of age.

335 Improvement in sleep quality, anxiety and depression in adults with moderate-to-severe atopic dermatitis with dupilumab treatment

Abstract Sleep disturbance is considered one of the most prevalent symptoms of atopic dermatitis (AD), and is associated with daytime sleepiness, anxiety and depression. In previous phase 3 trials, dupilumab treatment demonstrated significant improvement in objective AD signs and severity of symptoms, including sleep disturbance and mental health symptoms. To investigate the effect of dupilumab for up to 24 weeks on sleep quality, daytime sleepiness, anxiety and depression, using data from the DUPISTAD (NCT04033367) study. The randomized, phase 4 DUPISTAD study, was divided into two 12-week periods: an initial double-blind placebo-controlled period, and a subsequent 12-week open-label extension (OLE) period. The 24-week study enrolled adult patients with moderate-to-severe AD (Eczema Area and Severity Index score ≥12, Peak Pruritus Numeric Rating Scale [NRS] score ≥3, Sleep Disturbance NRS average score ≥5) who showed an inadequate response to topical treatments. These patients were randomized 2 : 1 to dupilumab 300 mg every 2 weeks (q2w) for both the double-blind and OLE periods or placebo for the initial double-blind period, followed by dupilumab 300 mg q2w for the OLE period. The use of concomitant topical corticosteroids was permitted as needed by both groups throughout the study. Endpoints included mean change from baseline to week 24 for Patient-Reported Outcome Measures Information System (PROMIS) Sleep T-score (standardized score ranging from 30 [best] to 80 [worst], with a mean of 50), Epworth Sleepiness Scale (ESS; scored 0–24; higher values indicate increased daytime sleepiness), and Hospital Anxiety and Depression Scale (HADS; scored 0–21; higher values indicate a worse outcome). Throughout the study, patients also completed a Sleep Diary, recording the NRS of restfulness upon waking up (scored 0–10; lower values indicate a worse outcome). Statistical comparisons were not performed on the data collected during the OLE observation period. A total of 188 patients were enrolled in the study: 127 received continuous dupilumab (dupilumab–dupilumab group) and 61 received placebo to week 12 and then dupilumab to week 24 (placebo–dupilumab group). Baseline demographics and disease characteristics were well balanced. Improvement from baseline in sleep quality, daytime sleepiness, anxiety and depression was observed at week 24 in both groups, as illustrated by the mean change from baseline in PROMIS Sleep T-scores (−12.5 in the dupilumab–dupilumab group and −11.7 in the placebo–dupilumab group), ESS scores (−4.6 in the dupilumab–dupilumab group and −3.7 in the placebo–dupilumab group), HADS anxiety scores (−3.8 in the dupilumab–dupilumab group and −4.4 in the placebo–dupilumab group), HADS depression scores (−4.4 in the dupilumab–dupilumab group and −3.4 in the placebo–dupilumab group), and the NRS of restfulness upon a waking-up item of the Sleep Diary (+3.3 in the dupilumab–dupilumab group and +3.4 in the placebo–dupilumab group). The improvement achieved by the placebo–dupilumab group converged with that of the dupilumab–dupilumab group during the OLE period, as shown by the mean change from week 12 to week 24 in PROMIS Sleep T-score (−3.8), ESS score (−1.9), HADS anxiety score (−1.6), HADS depression score (−0.9) and NRS of restfulness upon a waking-up item of the Sleep Diary (+1.5). The safety profile of dupilumab was consistent with the known safety profile. Dupilumab provided sustained improvement through 24 weeks in patient-reported measures of sleep, daytime sleepiness, anxiety, and depression in adult patients with moderate-to-severe AD. Patients who were switched from placebo to dupilumab at week 12 showed rapid improvement in these parameters after the switch, eventually matching the improvement achieved by patients who received dupilumab from baseline through week 24.

Practical Training Approaches for Discordant Atopic Dermatitis Severity Datasets: Merging Methods With Soft-Label and Train-Set Pruning.

Objective assessment of atopic dermatitis (AD) is essential for choosing proper management strategies. This study investigated the performance of convolutional neural networks (CNN) models in grading the severity of AD. Five board-certified dermatologists independently evaluated the severity of 9,192 AD images. The severity of AD was evaluated based on an Investigator's Global Assessment (IGA) and six signs of AD. For CNN training, we applied three distinct approaches: 1) ensemble vs. integration 2) hard-label vs. soft-label and 3) train-set pruning. For the IGA prediction, the two best models were chosen based on the macro-averaged AUROC and F-1 score. The ensemble-soft-label-pruning model was chosen based on AUROC 0.943, 0.927 for the internal and external validation set respectively, and integration-soft-label-whole dataset model was chosen based on the F1-score 0.750, 0.721 for the internal and external validation set respectively. CNN models trained by multi-evaluator dataset outperformed the models by an individual evaluator dataset, and they performed better to the dataset in which the assessment of dermatologists was concordant. In conclusion, CNN models for AD could be improved by labeled dataset from multiple evaluators, merging methods with soft-label and train-set pruning.

The use of hydrolyzed formulas as a method of correction of feeding and clinical rehabilitation of infants with atopy signs

Our study showed that in formula-fed babies, the use of mixture X (containing 2'-FL (2'-fucosyllactose) - a type of milk oligosaccharide, as well as carefully studied Bifidobacterium lactis, DHA, ARA, and nucleotides) as the main product for feeding could ensure children's body with all the necessary nutrients. Furthermore, it can minimize the progression of clinical signs of atopic dermatitis and reduce the use of drugs. In addition, there was an improvement in height and weight parameters, proportional development of the child (p<0.05), an increase in the number of erythrocytes (erythrocytes), hemoglobin (Hb), mean cell volume (MCV) (p<0.05), a decrease in the number of leukocytes (WBC) (p<0.05), and leveling of skin signs of atopic dermatitis (AD) (according to SCORAD a decrease from 32.8±5.5 to 16.1±2.2, p<0.05). Based on these results, it is possible to recommend using mixture (X) with a preventive and rational purpose as a product of artificial feeding of children with a hereditary predisposition to allergies.

EFFICACY OF DUPILUMAB IN INFANTS AND PRESCHOOLERS WITH ATOPIC DERMATITIS UP TO 1 YEAR

<h3>Introduction</h3> Continuous use of several traditional systemic atopic dermatitis (AD) treatments in pediatric patients is not recommended due to safety concerns and lack of long-term efficacy data. <h3>Methods</h3> Children aged 6 months to 5 years with moderate-to-severe AD who had participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434, part B; parent study) were enrolled into an open-label extension (OLE) study (NCT02612454). Patients received subcutaneous dupilumab every 4 weeks (200mg for children weighing 5 to <15kg; 300mg for 15 to <30kg). Topical AD treatments were allowed. <h3>Results</h3> Relative to parent study baseline, mean percentage changes (± standard error) in Eczema Area and Severity Index score were −41.6 (±4.6) and −54.0 (±3.2) at OLE baseline, −74.5 (±3.7) and −81.7 (±1.8) at Week 16, and −85.6 (±3.5) and −86.4 (±2.2) at Week 52 in the 200mg and 300mg dupilumab groups, respectively. The number of patients (%) achieving an Investigator's Global Assessment score of 0/1 increased from OLE baseline (6/61 [9.8%] and 15/116 [12.9%]), to Week 16 (22/58 [37.9%] and 35/115 [30.4%]), and at Week 52 (16/34 [47.1%] and 18/54 [33.3%]) in the 200mg and 300mg dupilumab groups, respectively. Overall safety of dupilumab treatment administered for up to 1 year was consistent with the known dupilumab safety profile. <h3>Conclusion</h3> Dupilumab treatment for 1 year provides sustained improvement in signs of AD in patients aged 6 months to 5 years with moderate-to-severe AD.

MEANINGFUL RESPONSES IN TRALOKINUMAB-TREATED ADOLESCENTS WITH ATOPIC DERMATITIS NOT ACHIEVING IGA 0/1 AT WEEK-16

<h3>Introduction</h3> In the monotherapy phase 3 trial (ECZTRA 6, NCT03526861) in adolescents with moderate-to-severe atopic dermatitis (AD) treated with tralokinumab, IGA of clear/almost clear skin (IGA 0/1) at Week 16 was a primary endpoint. IGA 0/1 can be a high standard to achieve for patients with moderate-to-severe AD and may not fully reflect achievement of other clinically meaningful parameters, such as improvement in signs, symptoms, and/or quality-of-life (QoL). <h3>Methods</h3> Adolescents (12-17 years) were randomized to subcutaneous tralokinumab 150mg or 300mg, or placebo, every 2 weeks. Patients who did not achieve IGA 0/1 at Week 16 and/or utilized rescue therapy were included in this <i>post-hoc</i> analysis. Non-responder imputation was used for patients who utilized rescue therapy or had missing data. Clinically meaningful responses were defined as EASI-50, ≥3-point improvement in pruritus NRS, or ≥6-point improvement in CDLQI. <h3>Results</h3> At Week 16, 78.6% and 82.5% of tralokinumab-treated patients (150mg/300mg) versus 95.7% (placebo) exhibited IGA>1 and/or used rescue therapy. 36.4% (150mg) and 52.5% (300mg) of patients with IGA>1 in the tralokinumab arms, compared to 21.1% (placebo), achieved clinically meaningful responses in at least one measure: EASI-50, pruritus NRS, or CDLQI. Greater proportions of tralokinumab-treated patients (150mg/300mg vs. placebo) achieved EASI-50 (31.2%/41.3% vs. 10.0%) and ≥3-point improvement in pruritus NRS (21.6%/22.8% vs. 8.0%). A greater proportion of tralokinumab 300mg patients vs. placebo (35.2% vs. 15.0%) achieved ≥6-point improvement in CDLQI. <h3>Conclusion</h3> Many tralokinumab-treated adolescents who did not achieve IGA 0/1 at Week 16 and/or used rescue therapy still achieved clinically meaningful improvements in AD signs, symptoms, and/or QoL.

Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis is Efficacious Regardless of Age of Disease Onset: a Post Hoc Analysis of Two Phase 3 Clinical Trials.

Adults with atopic dermatitis (AD) commonly report adult-onset disease. AD is associated with different genetics, lesion morphology and distribution, and symptoms by age of onset. Yet little is known about possible differences in treatment efficacy between adults with adult-onset or childhood-onset AD. We evaluated the efficacy of dupilumab by age of AD onset in adults with moderate-to-severe AD, using pooled data from the LIBERTY AD SOLO 1 and 2 studies (NCT02277743, NCT02277769). Results were stratified based on self-reported age of AD onset, divided into four age subgroups: 0-4, 5-9, 10-19, and over 20years. This analysis included 460 patients treated with placebo and 457 treated with dupilumab 300mg every 2weeks (q2w), with a mean patient age of 38years. Most patients (53.2%) reported AD onset at 0-4years, with 14% at 5-9years, 13.4% at 10-19years, and 18.5% at 20years or older. Dupilumab significantly improved AD signs and symptoms over 16weeks compared with placebo, regardless of age of onset. Dupilumab treatment resulted in a significantly greater proportion of patients achieving Eczema Area and Severity Index (EASI)-50, EASI-75, and EASI-90 (50%, 75%, and 90% improvement from baseline EASI, respectively), and clear or almost clear skin (Investigator's Global Assessment score 0 or 1) across all age-of-onset subgroups compared with placebo. In addition, EASI improvements were significant across all anatomical regions in all subgroups. Weekly average peak pruritus Numerical Rating Scale and Dermatology Life Quality Index also improved consistently and significantly with dupilumab versus placebo, regardless of age of onset. Despite possible differences in presentation and progression of AD linked to age of onset, dupilumab showed similar significant and sustained improvements in AD signs, symptoms, and quality of life in adults compared with placebo, over 16weeks of treatment. LIBERTY AD SOLO 1: NCT02277743; LIBERTY AD SOLO 2: NCT02277769. Infographic available for this article.

Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis.

Itch associated with atopic dermatitis (AD) has a profoundly negative effect on patients of all ages. Therefore, itch is a main target for AD therapeutic approaches, and treatments are perceived as beneficial when they achieve an itch reduction. In the absence of a validated scale for children aged 6-11years that is suitable for assessing itch intensity in clinical trial settings, the Worst Itch Scale was developed. Qualitative interviews, comprising concept elicitation and cognitive debriefing, were conducted to develop and evaluate the content validity of the Worst Itch Scale. Psychometric assessments used data from the LIBERTY AD PEDS phase 3 trial of dupilumab in patients aged 6-11years with severe AD. These included test-retest reliability, construct validity, known-groups validity and responsiveness. Thresholds for clinically meaningful change were defined using anchor- and distribution-based methods. The Worst Itch Scale consisted of two items asking about 'worst itching' experienced 'last night' and 'today'. Worst Itch Scale scores showed large, positive correlations with existing patient-reported outcome (PRO) measures of itch, and weaker correlations with clinician-reported outcome (ClinRO) measures assessing objective signs of AD. Improvements in Worst Itch Scale scores were highly correlated with improvements in other itch PROs and moderately correlated with improvements in ClinROs. The responder definition based on the primary anchor, a 1-point improvement in the Patient Global Impression of Disease, was 2.84. Supportive anchors produced response estimates ranging from 2.43 to 4.80 points. The Worst Itch Scale is a fit-for-purpose (e.g. well-defined, reliable, responsive and valid) scale for evaluating worst itch intensity in children aged 6-11years with severe AD. The within-patient threshold for defining a clinically meaningful response was a ≥ 3-4-point change in the Worst Itch Scale score. NCT03345914. Video: How can we reliably assess itch intensity in children 6-11 years with severe atopic dermatitis in clinical trial settings?

Phenotypic differences of atopic dermatitis stratified by age

Atopic dermatitis (AD) is common across all ages. Understanding heterogeneous age-related phenotypes may improve AD management. To determine age-related clinical phenotypes of AD. A prospective, dermatology practice-based study was performed (n= 380). AD severity was evaluated using questionnaires and full-body examination. Phenotypes were determined using latent class analysis. There were 23 (6.1%) pediatric patients (<18 years), 176 (46.3%) young adults (18-39 years), and 181 (47.6%) older adults (≥ 40 years). Both young and older adults experienced less AD on ankles (adjusted odds ratio [95% confidence interval]: 0.41 [0.19-0.90], 0.43 [0.20-0.94]), moderate-severe AD on flexures (0.47 [0.26-0.87], 0.30 [0.16-0.56]), pityriasis alba (0.24 [0.11-0.52], 0.07 [0.03-0.18]), oozing lesions (0.44 [0.25-0.79], 0.35 [0.20-0.63]), moderate-severe excoriations (0.49 [0.28-0.85], 0.44 [0.26-0.76]), and severe itch (adjusted β [95% confidence interval], -1.46 [-2.63 to -0.29]; -1.79 [-2.94 to -0.65]) compared with pediatric patients. Young adults experienced more AD around the eyes (2.92 [1.21-7.02]). Older adults experienced more AD on elbows (0.34 [0.19-0.64]), nipples (0.40 [0.16-0.99]), knees (0.27 [0.14-0.53]), keratosis pilaris (0.38 [0.15-0.98]), and lichenification (0.47 [0.22-0.98]). Four classes were identified for distribution of AD and associated signs. Distinct phenotypes exist by age with younger patients experiencing more AD signs and symptoms. Clinicians should consider them when managing AD.

A Heat-Killed Probiotic Mixture Regulates Immune T Cells Balance and IgE Production in House Dust Mite Extraction-Induced Atopic Dermatitis Mice.

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease accompanied with severe itching and skin lesions. Current studies have demonstrated that probiotics can exert an immunomodulatory effect, improve epithelial barrier function, and normalize the composition of gut microbiota. Thus, the aim of this study was to investigate the effect of probiotics on the immune balance of AD in vivo. We first screened two lactic acid bacteria strains, which were Lactococcus lactis subsp. cremoris MP01 and Lactobacillus paracasei subsp. paracasei MP02, from 10 strains isolated from traditional fermented milk with inflammation regulating activities in vitro. In the house dust mite (HDM) extraction-induced AD mouse model, mice were assigned randomly to four groups: control group (PC), HDM-induced AD group (NC), HDM-induced AD mice with administration of a mixture of heat-killed MP01 and MP02 at a low concentration (LD), and high concentration (HD) groups. Compared with the NC group, the probiotic treatments could relieve the AD symptoms. Moreover, the LD group significantly decreased total and HDM-specific IgE concentration. These results indicated that a combination of heat-killed MP01 and MP02 strains modulated the proportion of IL4+CD4+ T cells and IFNγ+CD4+ T cells in the spleen of HDM extraction-induced AD mice. In conclusion, administration of the heat-killed MP01 and MP02 mixtures appeared to relieve the classic AD signs, decrease serum IgE concentration, and rebalance the population of Th1/Th2 cells in HDM extraction-induced AD mice. The immunomodulatory activities of a combination of heat-killed MP01 and MP02 provided a potential new therapeutic strategy against AD.

Magnitude and Time Course of Response to Abrocitinib for Moderate-to-Severe Atopic Dermatitis

Emerging treatments for moderate-to-severe atopic dermatitis (AD) may provide greater and faster improvement in AD signs and symptoms than current therapies. To examine JADE COMPARE (NCT03720470) data using stringent efficacy end points. Adults with moderate-to-severe AD were randomly assigned 2:2:2:1 to receive oral abrocitinib 200 or 100 mg once daily, subcutaneous dupilumab 300 mg every 2 weeks (600-mg loading dose), or placebo, with medicated topical therapy for 16 weeks. Stringent response thresholds were applied for Eczema Area and Severity Index (EASI), Investigator's Global Assessment, Dermatology Life Quality Index, Peak Pruritus Numerical Rating Scale, and Night Time Itch Scale severity. At week 16, 48.9%, 38.0%, and 38.8% of the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, achieved greater than or equal to 90% improvement from baseline in EASI versus 11.3% placebo; 14.9%, 12.6%, and 6.5% achieved Investigator's Global Assessment 0 (clear) versus 4.8% placebo; 29.7%, 21.6%, and 24.0% achieved Dermatology Life Quality Index 0/1 (no/minimal impact on quality of life) versus 10.6% placebo; and 57.1%, 44.5%, and 46.1% achieved Night Time Itch Scale severity 0/1 (no/minimal night-time itch) versus 31.9% placebo. Kaplan-Meier median time to greater than or equal to 90% improvement from baseline in EASI was 59, 113, and 114 days in the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, and was not evaluable for placebo; median time to Peak Pruritus Numerical Rating Scale 0/1 (no/very minimal itch) was 86 and 116 days for abrocitinib 200-mg and dupilumab groups, respectively, and was not evaluable for abrocitinib 100-mg and placebo groups. A greater proportion of patients treated with abrocitinib than placebo had almost complete control of AD signs and symptoms.

Munich atopy prediction study (MAPS): protocol for a prospective birth cohort addressing clinical and molecular risk factors for atopic dermatitis in early childhood

IntroductionThe pathogenesis of atopic diseases is highly complex, and the exact mechanisms leading to atopic dermatitis (AD) onset in infants remain mostly enigmatic. In addition to an interdependent network of...

Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial

Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis. This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to <15 kg: 200 mg; bodyweight ≥15 kg to <30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434. Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p<0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p<0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation. Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults. Sanofi and Regeneron Pharmaceuticals.

34358 Long-term efficacy of dupilumab in adults with moderate-to-severe atopic dermatitis (AD): Results from an open-label extension (OLE) trial up to 4 years

Background: AD is a chronic systemic inflammatory disease often requiring long-term management. Here, we present long-term efficacy of dupilumab up to 4 years in adult patients with moderate-to-severe AD. Methods: The OLE (NCT01949311), with an initial duration of 3 years, enrolled adults with moderate-to-severe AD who participated in a dupilumab parent study. Protocol amendments extended the maximum treatment duration to 5 years. Following protocol amendments in 2017 and 2018, 114 and 272 patients re-entered the trial; 103 and 207 patients had a treatment interruption of >8 weeks between Weeks 148 and 164. Patients were treated with 300 mg dupilumab weekly. In 2019, patients transitioned to 300 mg every 2 weeks to align with approved dosage. Concomitant topical anti-inflammatory treatments were permitted. Data shown are for the overall study population (N = 2677). Results: 2207/1065/557/362/352 patients completed up to 52/100/148/172/204 weeks of treatment. 240 patients had treatment duration >204 weeks. Most withdrawals (59.5%) were due to dupilumab approval; 8.4%/4.3% withdrew due to adverse events/lack of efficacy. At Week 204, 95%/91%/76% of patients achieved 50%/75%/90% reductions in Eczema Area and Severity Index from parent study baseline (PSBL). 78.7%/70.8% of patients achieved ≥3/≥4-point reduction in the Peak Pruritus Numerical Rating Scale score from PSBL at Week 204. Treatment-emergent adverse events were reported in 2273 (84.9%) patients, with 99 (3.7%) permanently discontinuing treatment. Conclusions: Long-term dupilumab treatment showed sustained efficacy substantiated by improvement of AD signs and symptoms in patients with moderate-to-severe AD up to 204 weeks. Safety data were consistent with prior studies.