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Introduction: Standard therapy for patients with mild to moderate atopic dermatitis (AD) typically includes topical therapies; however, patients with more extensive AD and/or AD refractory to topical therapy may benefit from systemic treatment. Ruxolitinib cream monotherapy has demonstrated superior antipruritic and anti-inflammatory effects versus vehicle in patients with mild to moderate AD, and long-term disease control with as-needed use. Here, efficacy/safety of 1.5% ruxolitinib cream through 52 weeks was assessed in a subset of patients with moderate and/or more extensive disease. Methods: This post hoc analysis of TRuE-AD1/TRuE-AD2 included patients who, at baseline, had Investigator's Global Assessment (IGA) score of 3, Eczema Area and Severity Index (EASI) ≥ 16, and affected body surface area (BSA) ≥ 10% (higher severity of disease threshold subgroup). Disease control and safety were assessed. Results: Of 1249 patients in the overall population, 78 (6.2%) met all higher severity of disease threshold criteria (continuous-use vehicle-controlled period: 1.5% ruxolitinib cream, n = 32; vehicle, n = 13); 28 and 4 of these patients, respectively, continued as-needed 1.5% ruxolitinib cream during the long-term safety (LTS) period. At week 8 (continuous-use), IGA-treatment success (IGA 0/1, with ≥ 2-grade improvement from baseline) was achieved by 19/32 (59.4%) patients applying 1.5% ruxolitinib cream versus no patients applying vehicle. In the LTS period, those achieving clear/almost clear skin increased from 19/28 patients (67.9%; continuous-use: week 8) to 18/23 patients (78.3%; as-needed use: week 52) in patients applying ruxolitinib cream from day 1. Ruxolitinib cream was well tolerated, with few application site reactions, regardless of disease severity threshold. Efficacy and safety results were similar to the overall study population. Conclusion: Patients with AD who meet standard disease severity eligibility criteria for systemic therapy may achieve IGA-treatment success with clear/almost clear skin with continuous-use ruxolitinib cream, and maintain long term-disease control with as-needed ruxolitinib cream monotherapy. Trial Registration Number: NCT03745638/NCT03745651. Plain Language Summary: Atopic dermatitis (AD) is a skin condition that causes itchy, dry, and inflamed skin. For many people AD is controlled with medication that is applied to the skin. However, for some people medication that is taken orally or injected (i.e., systemic treatment) may be needed. Systemic treatment can sometimes be challenging. Doctors use a variety of tools to measure AD severity and apply standard criteria to help determine if a person should receive systemic treatment. In the TRuE-AD1/TRuE-AD2 clinical trials, itch and inflammation improved in people with mild to moderate AD after they applied ruxolitinib cream twice daily for 8 weeks. When people then applied ruxolitinib cream to areas of AD only when it was needed for another 44 weeks, ruxolitinib cream provided long-term control of their AD. The aim of this analysis was to assess disease control with ruxolitinib cream in people with AD severe enough to meet the standard criteria indicating a need for systemic treatment. In this group, the majority had clear or almost clear skin after applying ruxolitinib cream twice daily for 8 weeks. After 44 weeks of as-needed application of ruxolitinib cream, most people still had clear or almost clear skin. In this group of people who may have otherwise needed treatment with systemic therapy, ruxolitinib cream twice daily for 8 weeks and then as-needed was generally well tolerated. These results show that as-needed ruxolitinib cream may provide long-term control of AD in people who may otherwise have needed systemic therapy. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile. Objective: We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program. Methods: Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed. Results: Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 103/mm3 before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1]). Conclusions: This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.] Clinical Trial Registration: NCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026). Plain Language Summary: Abrocitinib is an approved treatment for people with moderate or severe atopic dermatitis, also known as AD or atopic eczema. Abrocitinib is a tablet that is taken by mouth once a day. This safety analysis looked at the side effects of treatment in a large group of adults and adolescents with moderate or severe AD who took abrocitinib up to a maximum of almost 4 years. This analysis also looked at which people were more likely to have certain side effects after taking abrocitinib. The results from this analysis were similar to those of previous safety analyses with abrocitinib, with no new side effects. Infections such as shingles, pneumonia, or herpes simplex can occur during treatment with abrocitinib. Shingles was more likely to occur in people who previously had shingles before taking abrocitinib, or who took the higher dose of abrocitinib (200 mg), or were 65 years of age or older, or had certain blood test results, or lived in Asia. People who are 65 years of age or older and took abrocitinib were more likely to develop some types of cancer, have certain abnormal blood test results, or develop blood clots in the veins than people with AD who were younger and took abrocitinib. Current or former smokers with AD who took abrocitinib were more likely to develop skin cancer (but not melanoma) than people with AD who took abrocitinib but have never smoked. This analysis further shows that abrocitinib had manageable safety in patients with moderate-to-severe AD. Dex5AhfAxs29XQspjFnxYi Video abstract: Integrated safety update of abrocitinib in 3802 patients with moderate-to-severe atopic dermatitis: data from more than 5200 patient-years with up to 4 years of exposure (MP4 63720 KB) [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD), a highly pruritic, inflammatory skin disease, affects approximately 7% of adolescents globally. A topical formulation of ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated safety and efficacy among adolescents/adults in two phase 3 studies (TRuE-AD1/TRuE-AD2). Objective: To describe safety and efficacy of 1.5% ruxolitinib cream versus vehicle and long-term disease control of ruxolitinib cream among adolescents aged 12–17 years from pooled phase 3 study data. Methods: Patients [≥ 12 years old with AD for ≥ 2 years, Investigator's Global Assessment score (IGA) 2/3, and 3–20% affected body surface area (BSA) at baseline] were randomized 2:2:1 to ruxolitinib cream (0.75%/1.5%) or vehicle for 8 weeks of continuous use followed by a long-term safety (LTS) period up to 52 weeks with as-needed use. Patients originally applying vehicle were rerandomized 1:1 to 0.75%/1.5% ruxolitinib cream. Efficacy measures at week 8 included IGA treatment success (IGA-TS; i.e., score of 0/1 with ≥ 2 grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index (EASI-75), and ≥ 4-point improvement in itch numerical rating scale (NRS4). Measures of disease control during the LTS period included IGA score of 0 (clear) or 1 (almost clear) and percentage affected BSA. Safety was assessed throughout the study. Results: Of 1249 randomized patients, 245 (19.6%) were aged 12–17 years. Of these, 45 patients were randomized to vehicle and 92 patients to 1.5% ruxolitinib cream. A total of 104/137 (75.9%) patients continued on 1.5% ruxolitinib cream in the LTS period [82/92 (89.1%) continued on 1.5% ruxolitinib cream; 22/45 (48.9%) patients on vehicle were reassigned to 1.5% ruxolitinib cream], and 83/104 (79.8%) of these patients completed the LTS period. At week 8, substantially more patients who applied 1.5% ruxolitinib cream versus vehicle achieved IGA-TS (50.6% versus 14.0%), EASI-75 (60.9% versus 34.9%), and NRS4 (52.1% versus 17.4%; P = 0.009). The mean (SD) reduction in itch NRS scores was significantly greater in patients applying 1.5% ruxolitinib cream versus vehicle from day 2 [− 0.9 (1.9) versus −0.2 (1.4); P = 0.03]. During the LTS period, mean (SD) trough steady-state ruxolitinib plasma concentrations at weeks 12/52 were 27.2 (55.7)/15.5 (31.5) nM. The percentage of patients achieving IGA score of 0 or 1 was sustained or further increased with 1.5% ruxolitinib cream; mean affected BSA was generally low (< 3%; i.e., mild disease). Through 52 weeks, application site reactions occurred in 1.8% of adolescent patients applying 1.5% ruxolitinib cream at any time; no patients had serious adverse events. There were no serious infections, malignancies, major adverse cardiovascular events, or thromboembolic events. Conclusions: Meaningful anti-inflammatory and antipruritic effects were demonstrated with 1.5% ruxolitinib cream in the subset of adolescent patients with AD, comparable with those observed in the overall study population; long-term, as-needed use maintained disease control and was well tolerated. Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03745638 (registered 19 November 2018) and NCT03745651 (registered 19 November 2018). [ABSTRACT FROM AUTHOR]

Purpose: Ruxolitinib (selective Janus kinase [JAK] 1 and JAK2 inhibitor) cream demonstrated efficacy and safety in patients with atopic dermatitis (AD) in the phase 3 TRuE-AD studies. In TRuE-AD1/ TRuE-AD2 (NCT03745638/NCT03745651), adults and adolescents with mild to moderate AD were randomized to apply twice-daily ruxolitinib cream or vehicle for eightweeks. Here, we evaluated the efficacy and tolerability of ruxolitinib cream by anatomic region, focusing on head/neck (HN) lesions that are typically difficult to manage and disproportionately affect quality of life (QoL). Materials and methods: Eczema Area and Severity Index (EASI) responses in anatomic regions were evaluated in the pooled population (N=1208) and among patients with baseline HN involvement (n=663). Itch, Investigator’s Global Assessment (IGA), QoL, and application site tolerability were also assessed. Results: By Week 2 (earliest assessment), ruxolitinib cream application resulted in significant improvements across all EASI anatomic region subscores and AD signs versus vehicle, with further improvements through Week 8. Significantly more patients with HN involvement who applied ruxolitinib cream versus vehicle achieved clinically meaningful improvements in itch, IGA, and QoL. Application site reactions with ruxolitinib cream were infrequent (<3%), including in patients with HN involvement. Conclusions: These results support the use of ruxolitinib cream for AD treatment across all anatomic regions, including HN. [ABSTRACT FROM AUTHOR]

Bermekimab is a human-derived recombinant monoclonal antibody that exhibits immunoregulatory activity by specifically blocking interleukin-1α activity. Four phase 2 studies evaluated efficacy and safety of bermekimab in patients with moderate-to-severe atopic dermatitis (AD). In addition, a novel human skin explant model was developed to assess bermekimab pharmacokinetics/pharmacodynamics and proteomic/transcriptomic effects. Study 1 (NCT03496974, N = 38) was an open-label, dose escalation study of subcutaneous bermekimab (200 mg or 400 mg). Study 2 (NCT04021862, N = 87) was a double-blind, placebo-controlled, randomized (1:1:1) study of subcutaneous bermekimab (400 mg every week (qw) or every 2 weeks) or placebo. GENESIS (NCT04791319, N = 198) was a double-blind, placebo- and active-comparator-controlled, randomized (1:1:2:2) study of placebo, subcutaneous bermekimab (350 mg or 700 mg qw), or dupilumab. LUNA (NCT04990440, N = 6) was a double-blind, placebo-controlled, randomized (4:1) study of intravenous bermekimab 800 mg qw or placebo. A novel human ex vivo skin pharmacodynamic assay supported phase 0 (NCT03953196) and phase 1 (NCT04544813) studies. In Study 1, 400 mg subcutaneous bermekimab showed improvement in efficacy assessments (e.g., ≥ 75% improvement of EASI over baseline, IGA 0/1, and worst itch); however, efficacy was not confirmed in Study 2 or GENESIS. Consequently, GENESIS and LUNA were terminated early. The novel human ex vivo skin pharmacodynamic assay demonstrated that bermekimab reduced downstream skin injury responses. Although bermekimab showed potential as an AD treatment in preclinical and early open-label trials, larger controlled studies (Study 2 and GENESIS) did not confirm those initial results. [ABSTRACT FROM AUTHOR]

Background Few large-scale international studies have broadly characterized the burden of atopic dermatitis (AD) across age groups among children and adolescents. Objectives To better characterize the AD burden in paediatric patients by disease severity. Methods This cross-sectional, web-based survey of paediatric patients (6 months to < 18 years old) was conducted in 18 countries representing North America, Latin America, Europe, Middle East/Eurasia and East Asia. Patients with diagnosed AD were identified based on the International Study of Asthma and Allergies in Childhood criteria and self-/parent-report of ever being told by a physician that they or their child had eczema. AD severity was assessed using the Patient-Oriented Eczema Measure and Patient Global Assessment. Outcomes included measures of itch, skin pain, sleep, health-related quality of life (HRQoL), missed school days and atopic comorbidities. Results The survey included 1489 children aged 6 months to < 6 years; 2898 children aged 6 to < 12 years; and 3078 adolescents aged 12 to < 18 years diagnosed with AD. Although the burden of mild AD was substantial, paediatric patients with moderate or severe AD had more itch, skin pain, sleep problems and impaired HRQoL, and missed more school days relative to those with mild AD; greater burden was observed among those with severe relative to moderate AD. At least one atopic comorbidity was present in 92.5% of all respondents. Conclusions These results highlight the burden of AD in paediatric patients, especially those with moderate-to-severe disease, and suggest the need for assessments that include the impact of AD on function and daily life. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is characterized by intense itch and other symptoms that negatively impact quality of life (QoL). This study evaluates the effect of upadacitinib (an oral selective Janus kinase inhibitor) monotherapy on patient-reported outcomes (PROs) among adults and adolescents with moderate-to-severe AD over 16 weeks. Methods: This integrated analysis of the double-blind, placebo-controlled periods of phase 3 monotherapy clinical trials Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) assessed itch (Worst Pruritus Numerical Rating Scale [WP-NRS] and SCORing Atopic Dermatitis [SCORAD]), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient-Oriented Eczema Measure), sleep (AD Impact Scale [ADerm-IS] and SCORAD), daily activities and emotional state (ADerm-IS), QoL (Dermatology Life Quality Index [DLQI] and Children's DLQI), mental health (Hospital Anxiety and Depression Scale), and patient impressions (Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment). Results: Data from 1683 patients (upadacitinib 15 mg, n = 557; upadacitinib 30 mg, n = 567; placebo, n = 559) were analyzed. A greater proportion of patients receiving upadacitinib versus placebo experienced improvements in itch (≥ 4-point improvement on WP-NRS) by week 1 (upadacitinib 15 mg, 11.2%; upadacitinib 30 mg, 17.7%; placebo, 0.5%; P < 0.001), with response rates sustained through week 16 (upadacitinib 15 mg, 47.1%; upadacitinib 30 mg, 59.8%; placebo, 10.4%; P < 0.001). Improvements were similar for PROs assessing skin pain/symptoms, sleep, daily activities, QoL, emotional state, mental health, and patient impressions of disease severity and treatment. Responses generally improved rapidly (within 1–2 weeks), increased through weeks 4–6, and were maintained through week 16. Conclusions: Once-daily oral upadacitinib monotherapy improved response rates across PROs compared with placebo. Upadacitinib therapy resulted in rapid, sustained improvements in PROs measuring symptom burden and QoL in adults and adolescents with moderate-to-severe AD. Trial Registration: ClinicalTrials.gov identifiers, NCT03569293 and NCT03607422. Plain Language Summary: Atopic dermatitis, or eczema, is characterized by itchy, dry, inflamed skin. These symptoms often make it difficult for patients to get adequate sleep. Patients with atopic dermatitis may also experience anxiety, depression, reduced self-confidence, social isolation, disruption to daily activities like school and work, and decreased quality of life. Many atopic dermatitis symptoms, including itch and psychological impact, are difficult for doctors to assess. Thus, it is important to consider patients' descriptions of their symptoms and quality of life, particularly when assessing treatment benefit. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. We investigated how upadacitinib (15 mg or 30 mg) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis in the Measure Up 1 and 2 clinical trials impacts their symptoms and quality of life over a 16-week period. We compared changes in patient-reported itch, pain, sleep, daily activities, emotional state, mental health, and overall quality of life among patients in the clinical trials who received upadacitinib with those in the same studies who received a dummy (placebo) treatment. Upadacitinib improved patient-reported symptoms and quality of life early in the clinical trials, often within the first 1–2 weeks. The extent of the improvements increased through weeks 4–6 of treatment and lasted through week 16. Patients who received upadacitinib reported greater improvements in symptoms and quality of life than did patients who received placebo. Upadacitinib treatment resulted in rapid and lasting improvements in the well-being of patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) affects multiple areas of the body, some of which may be more refractory to treatment. We evaluated improvements in the Eczema Area and Severity Index (EASI) by body region and clinical signs for each body region in lebrikizumab-treated patients with moderate-to-severe AD. Methods: ADvocate 1 and ADvocate 2 compared lebrikizumab 250 mg as monotherapy every 2 weeks versus placebo for 16 weeks. Efficacy measures included EASI, which rates the extent and severity of four clinical signs (erythema, edema/papulation, excoriation, lichenification) in four body regions (head/neck, upper extremities, trunk, lower extremities). Analyses are post hoc. Results: Mean baseline EASI, body region EASI subscores, and the severity of clinical signs were consistent across both studies (EASI ranging from 16.0 to 72.0). At week 16 in both studies, patients treated with lebrikizumab showed significantly greater percent improvement in EASI across all body regions versus placebo (p ≤ 0.001), with improvements as early as week 2. In ADvocate 1, all clinical signs significantly improved across all body regions at week 16 with lebrikizumab (51.4–71.6% improvement) versus placebo (23.1–43.5%, p ≤ 0.001), with significant improvements as early as week 2 for all signs. Significant improvements for all clinical signs at week 16 were also seen in ADvocate 2 for lebrikizumab (53.5–75.6%) versus placebo (28.5–41.2%, p ≤ 0.001) and as early as week 2 for all body regions and signs except head/neck erythema and lower extremity erythema, edema/papulation, and lichenification, which showed significant improvement by week 4. Conclusions: Lebrikizumab as monotherapy consistently and rapidly reduced the extent of involvement and severity of AD in all EASI clinical signs and body regions, including the head and neck region and clinical sign of lichenification, compared with placebo. Trial Registration: ClinicalTrials.gov identifier: ADvocate 1 (NCT04146363) and ADvocate 2 (NCT04178967). [ABSTRACT FROM AUTHOR]

Introduction/Background Biologics and Janus kinase inhibitors (JAKi) are promising treatment options for patients with atopic dermatitis (AD)1; however, no studies, to our knowledge, have evaluated differences in characteristics of patients on these medications in a real-world setting. Objective This study sought to describe the demographics, clinical characteristics, treatment patterns, and disease severity and patient-reported outcome measures of adult patients with AD initiating either a biologic or JAKi in the prospective, non-interventional CorEvitas AD Registry. Methods This cross-sectional study included patients initiating either a biologic (dupilumab or tralokinumab) or JAKi (abrocitinib or upadacitinib) in the CorEvitas AD Registry between 7/21/2020 and 7/31/2023. Patient characteristics were summarized at initiation of therapy using descriptive statistics, overall and by prior experience with biologic/JAKi therapy and systemic therapy (any registry-eligible systemic medication). Additionally, exploratory multivariable modified-Poisson regression was used to identify factors associated with biologic vs. JAKi initiation. Variables were selected by first using bivariate regression, and covariates with p-values ≤0.15 were submitted to a backward selection process. Age, sex, and race were included in the final model for representation purposes. Results The study reported 1,958 initiations, with 1,604 biologic initiations and 354 JAKi initiations. The initiated medication was the first-line systemic among 86.4% of the biologic initiators and 40.7% of the JAKi initiators. Biologic initiators were slightly older than JAKi initiators (mean age 50.7 years, SD 18.5 vs. mean 47.9, SD 17.0 years), with no major differences in sex, race/ethnicity, education, or work status. Differences were seen in history of infections (32.7% in biologic initiators vs. 44.9% in JAKi initiators) and rosacea (12.1% biologics vs. 5.9% JAKi). Furthermore, biologic initiators had greater disease severity than JAKi initiators as measured by body surface area % involvement (mean 26.0, SD 20.2 vs. mean 18.3, SD 19.4), validated Investigator Global Assessment for AD (severe vIGA-AD™, 34.4% vs. 24.6%), Eczema Area and Severity Index (EASI, mean 14.5, SD 12.0 vs. mean 10.7, SD 11.1) and SCoring AD (SCORAD, mean 48.2, SD 19.8 vs. mean 42.2, SD 20.1). Patient-reported outcomes were similar between groups. In adjusted analyses, factors positively associated with JAKi initiation compared to biologics included living in the Midwest US (vs. Northeast US, RR: 1.50, 95% CI: 1.14, 1.97), worst skin pain in 24 hours (RR: 1.05, 95% CI: 1.02, 1.09), and prior use of 1 or 2+ systemic therapies (vs. none, RR: 4.30, 95% CI: 2.29, 8.07 and RR: 5.49, 95% CI: 3.06, 9.84, respectively). Factors positively associated with biologic initiation included having a history of cancer (RR: 0.33, 95% CI: 0.22, 0.49), moderate vIGA-AD™ (vs. clear, RR: 0.74, 95% CI: 0.56, 0.98), hand involvement (RR: 0.73, 95% CI: 0.62, 0.86), and worst itch in 24 hours (RR: 0.97, 95% CI: 0.94, 0.99). Conclusions In this real-world assessment, certain characteristics differed between adult patients with AD initiating either biologics which were most commonly first-line agents or JAKi (more likely used after other systemic agents), although some effect sizes were small and may not be clinically meaningful. Study limitations to consider include that characteristics associated with biologic or JAKi initiation may be influenced by timing of medication approval and availability. These foundational results highlight the importance of individualized patient assessment when deciding among different therapeutic approaches. [ABSTRACT FROM AUTHOR]

The article discusses the adoption and use of the vIGA-AD scale, a validated scale for measuring the severity of atopic dermatitis (AD). The scale was developed in 2016 to provide a standardized and representative measure of AD severity. The study analyzed data from ClinicalTrials.gov and PubMed to assess the scale's uptake in the AD research community. The results showed an increase in the proportion of studies and publications using the vIGA-AD scale over the years. The article also highlights the limitations of the scale and suggests using it in combination with other outcome measures. The authors conclude that the vIGA-AD scale has been widely adopted by researchers and sponsors as a validated measure of AD severity. [Extracted from the article]

Background and Objective: Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) is a difficult endpoint to achieve after short-term treatment of chronic moderate-to-severe atopic dermatitis, and does not fully reflect clinically meaningful changes in other parameters. We assessed the impact of tralokinumab versus placebo on other clinically meaningful parameters in patients not achieving IGA 0/1 at week 16 using pooled data from two monotherapy phase III trials, ECZTRA 1 and 2. Methods: This post hoc analysis included patients (n = 1328) from ECZTRA 1 and 2 who did not achieve the co-primary endpoint, IGA 0/1 at week 16 without rescue medication. Endpoints evaluating atopic dermatitis extent and severity included proportions of patients achieving IGA 0/1, 50%, 75%, and 90% improvement in Eczema Area and Severity Index (EASI-50/75/90); endpoints evaluating patient-reported outcomes included a ≥ 3-point improvement in worst daily pruritus Numerical Rating Scale (NRS), a ≥ 3-point improvement in eczema-related sleep interference (sleep) NRS, a ≥ 4-point improvement in Dermatology Life Quality Index (DLQI), and DLQI ≤ 5. Specifically, clinically meaningful responses were defined as EASI-50, a ≥ 3-point improvement in itch NRS, or a ≥ 4-point improvement in DLQI at week 16. Results: Among ECZTRA 1 and 2 patients who did not achieve IGA 0/1 at week 16 without rescue medication, a significantly greater proportion of patients receiving tralokinumab versus placebo achieved EASI-50 (33.0% vs 13.0%), a ≥ 3-point improvement in itch NRS (22.6% vs 9.4%), or a ≥ 4-point improvement in DLQI (41.2% vs 24.5%) at week 16. In addition, compared with placebo, a numerically greater proportion of tralokinumab-treated patients achieved all three measures of clinically meaningful response (30% vs 18%) or a clinically meaningful change in at least one outcome (48.8% vs 28.5%). Significantly greater proportions of patients receiving tralokinumab versus placebo achieved additional clinician-reported and patient-reported outcomes, such as EASI-75 (13.5% vs 4.1%), EASI-90 (3.5% vs 1.1%), DLQI ≤ 5 (22.5% vs 12.5%), and a ≥ 3-point improvement in sleep NRS (24.5% vs 11.5%). Conclusions: Tralokinumab provided clinically meaningful responses in patients with moderate-to-severe atopic dermatitis who did not achieve IGA 0/1 at week 16 and/or used rescue medication. Using multiple validated outcome measures of both efficacy and quality of life, alongside IGA scores, can better characterize tralokinumab treatment responses in patients with moderate-to-severe atopic dermatitis. [Video abstract available] Clinical Trial Registration: NCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study completion date: 10 October, 2019. NCT03160885 (ECZTRA 2); study start date: 12 June, 2017; primary completion date: 4 September, 2019; study completion date: 14 August, 2019. 6QcTdZHHiWG8xHjHtHEVo6 Video abstract: Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1 (MP4 362818 KB) [ABSTRACT FROM AUTHOR]

Introduction: There is a scarcity of data beyond 1 year for the use of dupilumab to treat atopic dermatitis (AD) in a real-world setting. This study aimed to evaluate the 2-year effectiveness of dupilumab among adult and pediatric patients with moderate-to-severe AD included in a real-world, longitudinal database study. Methods: PROSE is an ongoing, prospective, observational, multi-center registry in the USA and Canada, designed to collect real-world data from patients aged ≥ 12 years with moderate-to-severe AD who initiate dupilumab in accordance with country-specific prescribing information. Assessments include body surface area affected by AD (BSA), Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), Pruritus Numerical Rating Scale (P-NRS), Patient-Oriented Eczema Measure (POEM), Patient Global Assessment of Disease (PGAD) questionnaire score, and occurrence of adverse events (AEs). Results: Of 764 patients who enrolled in PROSE, 632 (83%) remained in the study at the time of this interim analysis. Improvements were observed at the first post-baseline clinic visit (approximately 3 months) in the clinician-assessed measures (mean BSA and EASI scores); improvements were sustained throughout the 2-year period covered in the present study. Consistent and sustained improvements were also observed over the 2-year period in the patient-reported measures of P-NRS, POEM, and DLQI, and in the proportion of patients reporting "very good/excellent" in answer to the question in the PGAD questionnaire: "Considering all the ways in which your eczema affects you, indicate how well you are doing". Dupilumab treatment was well tolerated, with safety findings consistent with those previously reported in studies of dupilumab for the treatment of AD. Conclusions: In the real-world PROSE registry, patients with moderate-to-severe AD experienced sustained improvement in disease control, symptoms, and quality of life up to 2 years after initiating dupilumab treatment. Safety data were consistent with the known safety profile of dupilumab. Trial Registration: ClinicalTrials.gov identifier: NCT 03428646. 5v18Ci3NqU6719FdQ_Njj3 Video abstract (MP4 20,717 kb) Plain Language Summary: Atopic dermatitis (AD) is a long-term disease that affects the skin of patients, causing rash, inflammation, and intense itching, all leading to profound negative effects on their quality of life. In short-term studies, dupilumab has been shown to improve the signs and symptoms of AD, and to improve patients' quality of life. However, there is currently little information about the effectiveness of dupilumab when patients use it over the long term in the real world. This study used data from the ongoing PROSE registry, which is collecting information on 764 adults and adolescents (aged ≥ 12 years) with moderate-to-severe AD who are using dupilumab in the real world; patients were allowed to use other AD treatments and could even stop using dupilumab. Most patients (83%) were evaluated after 2 years of treatment. The study looked at how physicians judged changes over time in the severity of patients' AD. Importantly, it also used measures to allow patients themselves to report how they felt treatment affected their AD, the amount of itch they experienced, and their quality of life. Improvements in the severity of AD were already seen at 3 months, and they were maintained over the 2-year period. Patients also reported consistent and sustained improvements in their AD symptoms and quality of life during the 2 years of treatment. This analysis shows that patients with AD who began dupilumab treatment can have sustained long-term improvements. [ABSTRACT FROM AUTHOR]

This article discusses the evaluation of the Atopic Dermatitis Control Tool (ADCT), a patient-reported outcome instrument used to assess patient-perceived disease control in atopic dermatitis (AD). The study found that the ADCT had strong internal consistency and construct validity in both adult and adolescent populations. It suggests that the ADCT can improve patient-clinician communication and inform disease-management decisions. However, the small sample size limits the generalizability of the findings. The article also mentions that B.L. is involved with several pharmaceutical companies in various capacities, which may be relevant for patrons researching pharmaceutical companies and their collaborations with medical professionals. [Extracted from the article]

The original article can be found online at https://doi.org/10.1007/s13555-023-01061-4.Publisher Correction to: Dermatol Ther (Heidelb) (2024) 14:261–270https://doi.org/10.1007/s13555-023-01061-4The infographic was missing from this article and should have appeared as below.InfographicGraphThe original article has been corrected.By Eric L. Simpson; Ben Lockshin; Lara Wine Lee; Zhen Chen; Moataz Daoud and Andrew KorotzerReported by Author; Author; Author; Author; Author; Author [Extracted from the article]

Background: Two phase III trials, ECZTRA 1 and 2, confirmed the efficacy and safety of tralokinumab versus placebo in adults with moderate-to-severe atopic dermatitis (AD). To further explore the long-term efficacy of tralokinumab for AD, a pooled analysis of these trials was conducted. Methods: ECZTRA 1 and 2 patients (n = 1596 total) were randomized to tralokinumab 300 mg or placebo every 2 weeks (q2w) over 16 weeks. Patients achieving Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) and/or 75% improvement in the Eczema Area and Severity Index (EASI-75) at Week 16, were re-randomized to tralokinumab q2w, every 4 weeks (q4w), or placebo (tralokinumab withdrawal) for another 36 weeks. Patients not achieving the response criteria at Week 16 received open-label tralokinumab q2w plus optional topical corticosteroids (TCS). A pooled, prespecified analysis assessed the proportions of Week 16 responders that maintained IGA 0/1 and/or EASI-75 at Week 52. Pooled data from all patients initiated with tralokinumab, regardless of the response at Week 16 or dosing regimen received thereafter, were analyzed post hoc. Results: In patients who achieved the primary endpoints at Week 16, IGA 0/1 responses were maintained at Week 52 without rescue treatment (including TCS) by 55.9%, 42.4%, and 34.0% of patients re-randomized to tralokinumab q2w, q4w, or placebo (tralokinumab withdrawal), respectively, while EASI-75 responses were maintained by 57.3%, 50.4%, and 26.4%, respectively (prespecified analysis). In a post hoc analysis of all patients initiated with tralokinumab, response rates improved over time with continued tralokinumab treatment beyond Week 16 to Week 52 for EASI-50 (63.1–82.7%), EASI-75 (37.6–61.8%), EASI-90 (20.4–37.3%), and IGA 0/1 (23.0–36.2%). Conclusions: Tralokinumab treatment provides progressive and sustained improvement over 1 year in the extent and severity of AD in patients with moderate-to-severe AD. Clinical Trial Registration: NCT03131648 (ECZTRA 1); study start date: 30 May 2017; primary completion date: 7 August 2018; study completion date: 10 October 2019. NCT03160885 (ECZTRA 2); study start date: 12 June 2017; primary completion date: 4 September 2019; study completion date: 14 August 2019. Infographic: Plain Language Summary: Atopic dermatitis (AD) is a chronic inflammatory disease characterized by excessively dry and itchy skin, resulting in a considerable burden of disease. Patients with AD often require long-term treatment. Tralokinumab is an injectable antibody treatment that targets a protein called interleukin-13, which substantially contributes to the signs and symptoms of AD. In the ECZTRA 1 and 2 phase III clinical trials, funded by LEO Pharma A/S, adults with moderate-to-severe AD treated with tralokinumab every other week for 16 weeks showed significant improvement in disease extent and severity compared with patients receiving placebo. To further explore the long-term efficacy of tralokinumab for AD, we performed a new analysis combining the almost 1600 patients of ECZTRA 1 and 2. A large proportion of patients treated with tralokinumab who achieved clear or almost clear skin at Week 16 were able to maintain clear or almost clear skin at Week 52 with less frequent dosing (every 4 weeks). Additionally, combining all patients treated with tralokinumab, regardless of Week 16 response or dose frequency thereafter, showed that most patients achieved a significant reduction in disease extent and severity at Week 52. These results demonstrate that many tralokinumab-treated patients continue to improve beyond Week 16, and highlight that efficacy results at Week 16 may not be representative of the outcome of longer-term tralokinumab treatment. These findings may help health care providers better advise patients regarding when to modify treatment with tralokinumab. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, inflammatory, intensely pruritic skin disorder associated with significant patient burden. Interleukin (IL)‐13 is a cytokine that acts as a driver of immune dysregulation, skin‐barrier dysfunction, and microbiome dysbiosis that characterizes AD, and is consistently overexpressed in AD skin. Tralokinumab is a fully human immunoglobulin (Ig) G4 monoclonal antibody that binds specifically to IL‐13 with high affinity, thereby inhibiting subsequent downstream IL‐13 signaling. Three pivotal phase 3 clinical trials demonstrated that tralokinumab 300 mg every other week, as monotherapy or in combination with topical corticosteroids as needed, provides significant improvements in signs and symptoms of moderate‐to‐severe AD, as measured by Investigator's Global Assessment 0/1 (clear/almost clear) and Eczema Area and Severity Index‐75 at Week 16. Improvements were observed soon after tralokinumab initiation and were maintained over 52 weeks of therapy. Tralokinumab significantly improved patient‐reported outcomes such as itch and sleep, and demonstrated a safety profile comparable with placebo; conjunctivitis during tralokinumab therapy was generally mild. Similar results were observed in a phase 3 adolescent trial. The role of IL‐13 in the pathophysiology of AD justifies a targeted approach and a wealth of clinical data supports tralokinumab as a new therapeutic option for people with moderate‐to‐severe AD. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is heterogeneous in distribution pattern and clinical features. This analysis assessed the effect of dupilumab on the extent and severity of AD across various signs (erythema, edema/papulation, excoriation, lichenification) in different anatomical regions (head and neck, trunk, upper extremities, lower extremities) in patients aged 6 months to 5 years. Methods: In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo with concomitant low-potency topical corticosteroids (TCS) every 4 weeks for 16 weeks. Changes in AD signs across anatomical regions were assessed using unweighted Eczema Area and Severity Index (EASI) body region scores. Results: Overall, 162 patients were randomized to dupilumab (n = 83) or placebo (n = 79). A significant improvement in least squares mean EASI area score was seen by week 2 in all four anatomical regions (P < 0.0001 for dupilumab vs. placebo) and sustained throughout treatment. Least squares mean EASI sign scores in erythema, excoriations, and infiltration/papulation showed significant improvement by week 2 in all regions (P < 0.001), while lichenification showed significant improvement in all regions by week 4 (P < 0.001). Conclusion: Dupilumab use with concomitant low-potency TCS treatment resulted in rapid and consistent improvement in AD signs in all anatomical regions, in patients aged 6 months to 5 years with moderate-to-severe AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03346434 Part B. [ABSTRACT FROM AUTHOR]

Background: Traditional systemic immunosuppressants and advanced therapies improve signs and symptoms of moderate-to-severe atopic dermatitis (AD). However, data are limited in severe and/or difficult-to-treat AD. In the phase 3 JADE COMPARE trial of patients with moderate-to-severe AD receiving background topical therapy, once-daily abrocitinib 200 mg and 100 mg showed significantly greater reductions in the symptoms of AD than placebo and significantly greater improvement in itch response (with abrocitinib 200 mg) than dupilumab at week 2. Objective: This study assessed the efficacy and safety of abrocitinib and dupilumab in a subset of patients with severe and/or difficult-to-treat AD in a post hoc analysis of the JADE COMPARE trial. Methods: Adults with moderate-to-severe AD received once-daily oral abrocitinib 200 mg or 100 mg, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo with concomitant medicated topical therapy. Severe and/or difficult-to-treat AD subgroups were classified by baseline characteristics [Investigator's Global Assessment (IGA) 4, Eczema Area and Severity Index (EASI) > 21, failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids), percentage of body surface area (%BSA) > 50, upper quartiles of EASI (EASI > 38) and %BSA (%BSA > 65), and combined subgroup of IGA 4, EASI > 21, and %BSA > 50, and failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids)]. Assessments included IGA score of 0 (clear) or 1 (almost clear) and a ≥ 2-point improvement from baseline, ≥ 75% and ≥ 90% improvement from baseline in EASI (EASI-75 and EASI-90), ≥ 4-point improvement from baseline in Peak Pruritus-Numerical Rating Scale (PP-NRS4), time to PP-NRS4, least squares mean (LSM) change from baseline in 14-day PP-NRS (days 2–15), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI) up to week 16. Results: The proportion of patients achieving IGA 0/1, EASI-75, and EASI-90 responses was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.05) across all subgroups with severe and/or difficult-to-treat AD. Across most subgroups, PP-NRS4 response was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.01); the time to achieve this response was shorter with abrocitinib 200 mg (range 4.5–6.0 days) than abrocitinib 100 mg (range 5.0–17.0 days), dupilumab (range 8.0–11.0 days), and placebo (range 3.0–11.5 days). LSM change from baseline in POEM and DLQI was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.001) across all subgroups. Clinically meaningful differences were observed between abrocitinib and dupilumab for most evaluated endpoints across several subgroups, including in patients who failed or were intolerant to prior systemic therapy. Conclusions: Abrocitinib provided rapid and substantially greater improvements in skin clearance and quality of life compared with placebo and dupilumab in subgroups of patients with severe and/or difficult-to-treat AD. These findings support the use of abrocitinib for severe and/or difficult-to-treat AD. Trial registration: ClinicalTrials.gov, NCT03720470. Plain Language Summary: Atopic dermatitis (AD), also known as atopic eczema, is a skin disease that causes itchy and red skin patches. People can be diagnosed with severe and/or difficult-to-treat AD if their signs and symptoms of AD are extremely severe and their AD cannot be adequately treated by common medicines. Abrocitinib is a treatment that has been shown in clinical trials to improve the symptoms of AD. We analyzed data from the JADE COMPARE study, which included 837 people who were treated with abrocitinib, dupilumab (another treatment for AD), or placebo. Many of these people had severe symptoms when they entered the study. Some had AD signs and symptoms that did not improve after they took common medicines for AD. We studied how well abrocitinib worked in these people with severe and/or difficult-to-treat AD. We found that these people achieved clear skin and itch relief at week 16 after treatment with abrocitinib 200 mg compared with placebo (no drug control). Additionally, they achieved significant relief from itch faster with abrocitinib 200 mg compared with abrocitinib 100 mg, dupilumab, or placebo. People reported less severe AD and better quality of life after treatment with abrocitinib compared with placebo. Together, the findings of our study provide important evidence for healthcare providers as they determine a treatment plan for people with severe and/or difficult-to-treat AD. [ABSTRACT FROM AUTHOR]

Introduction/Background Lebrikizumab (LEB) is a novel monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) are identically designed Phase 3 trials that evaluated LEB as a monotherapy treatment for moderate-to-severe atopic dermatitis (AD). Many patients who met the protocol-defined response criteria at Week 16, defined as achieving ≥75% improvement in the Eczema Area and Severity Index (EASI 75) or an Investigator's Global Assessment of 0 or 1 (IGA 0/1) without use of rescue therapy, maintained a deep response up to Week 521. Deep response was defined as maintaining an IGA 0 (clear skin), a 100% improvement in the Eczema Area and Severity Index (EASI 100), or a Pruritus Numeric Rating Scale score of 0 or 1 (Pruritus NRS 0/1). Patients completing Week 52 were given the option to roll over into a long-term extension (LTE) study, ADjoin (NCT04392154), allowing the opportunity to analyze deep response for a longer period of time. This analysis supports the evolution of AD treatment goals toward maintaining higher efficacy thresholds for a longer duration. Objectives To present the long-term maintenance of LEB's depth of response for up to 104 weeks of treatment (52 weeks in the ADvocate studies and 52 weeks in the ADjoin study). Methods Patients entering ADjoin from ADvocate1 and ADvocate2 continued taking the same LEB dose as the parent study. Patients receiving placebo (LEB withdrawal) during the maintenance period of ADvocate1 and ADvocate2 transitioned to receive LEB every 2 weeks (Q2W) during ADjoin (data not included in this analysis). The proportion of patients achieving IGA and EASI responses were calculated from the LEB-treated patients who were IGA 0/1 or EASI 75 responders, respectively, at Week 16 in ADvocate1 and ADvocate2. The proportion of patients achieving a Pruritus NRS 0/1 response were calculated from the LEB patients who were per protocol responders at Week 16 of ADvocate1 and ADvocate2. Each patient's absolute Pruritus NRS score was calculated by averaging daily scores from the previous seven days with at least one nonmissing value. The weekly score was then rounded to the nearest integer. Consistent with common reporting practices for LTE studies, this post hoc analysis reports observed data which were analyzed regardless of rescue medication use or treatment discontinuation. Results From Week 52 to Week 104, the proportion of IGA 0 responders was maintained and slightly increased in patients treated with LEB Q2W (50.8% [N=59] to 52.3% [N=44]) and LEB every 4 weeks (Q4W; 43.5% [N=69] to 45.5% [N=55]). Greater improvements over the second year of treatment were seen in the proportion of EASI 100 responders treated with LEB Q2W (36.4% [N=88] to 39.7% [N=68]) and LEB Q4W (30.7% [N=101] to 41.3% [N=80]) as well as the proportion of Pruritus NRS 0/1 responders treated with LEB Q2W (46.3% [N=80] to 57.4% [N=61]) and Q4W (47.9% [N=94] to 55.4% [N=65]). Although rescue medication was allowed during ADjoin, a relatively low proportion of patients received ≥1 topical rescue medication in the LEB Q2W (9.8%) and LEB Q4W (15.2%) treatment arms. Conclusions These 2-year results demonstrate an extended maintenance of deep response in patients treated with LEB Q2W and LEB Q4W after responding to 16 weeks of LEB Q2W. Approximately 50% and 40% of LEB-treated patients sustained total skin clearance (IGA 0 and EASI 100, respectively) and more than 55% of LEB-treated patients reported no or minimal itch (Pruritus NRS 0/1). Maintenance treatment with LEB Q2W and LEB Q4W allows patients and providers to elevate their expected treatment goals in AD beyond EASI 75 and IGA 0/1 response. [ABSTRACT FROM AUTHOR]

Introduction/Background Tralokinumab is a high-affinity monoclonal antibody that specifically targets interleukin (IL)-13, a key driver of atopic dermatitis (AD). In clinical trials, tralokinumab demonstrated efficacy and a favorable safety profile for the treatment of moderate-to-severe AD in adults and adolescents. However, data on patients in the real-world setting and persistence to treatment is currently limited. Objectives To describe the baseline characteristics and persistence at 6 months of treatment in US adult patients with AD initiating tralokinumab in the CorEvitas AD registry. Methods The CorEvitas Atopic Dermatitis Registry is a prospective, non-interventional registry launched in July 2020 for adult AD patients under the care of a licensed dermatologist or qualified dermatology practitioner. Data are collected from both patients and providers approximately every 6 months during routine clinical encounters. This analysis included U.S. patients enrolled in the CorEvitas AD registry who initiated tralokinumab between February 1, 2022 (the commercial launch date) and May 31, 2023 and had baseline data. Baseline demographics and clinical characteristics were summarized using descriptive statistics and stratified by advanced systemic therapy (AST) experience, defined as any previous history of dupilumab, abrocitinib, or upadacitinib for AD treatment. A 6-month follow-up visit was defined as a visit occurring 5 to 9 months following tralokinumab initiation. Results Among 259 included patients in this study the mean age was 50.8 years. The majority of patients were female (156/259, 60.2%), White (202/259, 78.0%), worked full-time (143/259, 55.2%), had private health insurance (201/259, 77.6%), and were concomitantly on topical therapy (203/259, 78.4%). Most patients had moderate-to-severe disease, with mean Eczema Area and Severity Index (EASI) of 14.2. Approximately half of patients reported AD involvement of head (face: 121/259, 46.7%; scalp: 80/259, 30.9%; neck: 93/259, 35.9%) and hands (dorsal: 150/259, 57.9%; palmar: 130/259, 50.2%). Patients reported high symptomatic disease burden, demonstrated by mean peak pruritus in past 24 hours numerical rating scale (NRS) of 6.2, and moderate impact on quality of life, as demonstrated by mean Dermatology Life Quality Index (DLQI) of 9.8. At tralokinumab initiation, 87 patients (33.6%) were AST-experienced, of whom 95.4% (83/87) had used dupilumab. Among AST-naïve patients, 80.8% (139/172) had used super potent topical steroids, 36.0% (62/172) topical calcineurin inhibitors, and 10.5% (18/172) topical PDE4 inhibitors. Overall, socio-demographic characteristics were similar between AST-naïve and AST-experienced groups, while AST-naïve patients had higher disease severity at initiation, including mean BSA (29.4% vs. 16.9%) and mean EASI (16.9 vs. 8.8). Among patients with a 6-month follow-up visit (n=81), 74.1% (60/81) remained persistent on tralokinumab. Baseline characteristics of patients with 6-month follow-up, and of persistent patients, were similar to the total population. Among persistent patients, 73.3% (44/60) were AST-Naïve and 26.7% (16/60) were AST-experienced, all of whom were dupilumab-experienced. Mean EASI among persistent patients improved from 13.8 at baseline to 3.3 at 6 months. Of the 21 patients who discontinued tralokinumab, 52.4% (11/21) were AST-experienced at initiation, and 42.9% (9/21) switched to another systemic therapy following tralokinumab. Reasons for discontinuation included lack of efficacy (AST-naïve: 30.0%, 3/10; AST-experienced: 45.5%, 5/11), safety (AST-naïve: 30.0%, 3/10; AST-experienced: 9.1%, 1/11), insurance (AST-naïve: 10.0%, 1/10; AST-experienced: 9.1%, 1/11), and other (AST-naïve: 30.0%, 3/10; AST-experienced: 36.4%, 4/11). Conclusions In this US real-world study, adult AD patients initiating tralokinumab were both AST-naïve and AST-experienced with a high burden of disease. Approximately three-quarters of patients were persistent with tralokinumab treatment at 6 months. Further real-world evidence studies on tralokinumab persistence with longer follow-up period are warranted. [ABSTRACT FROM AUTHOR]

Introduction/Background While previous studies into continuous long-term dupilumab treatment for adults with moderate-to-severe atopic dermatitis (AD) demonstrated sustained efficacy, further study into long-term safety and efficacy data regarding dupilumab in children is needed. Objectives To evaluate the impact of treatment with dupilumab and low-potency topical corticosteroids (TCS) for up to 2 years on efficacy and safety measures in children aged 6 months to 5 years with moderate-to-severe AD. Methods Children aged 6 months to 5 years with moderate-to-severe AD, who had participated in prior dupilumab pediatric AD studies were enrolled in a phase 3 open label extension (OLE) study. Patients received subcutaneous dupilumab every 4 weeks; 200 mg for children weighing 5 to <15 kg, 300mg for 15 to <30 kg. Topical AD treatments were allowed. Efficacy outcomes assessed include the proportion of patients who achieved 75% improvement from baseline in Eczema Area and Severity Index (EASI-75) score and the proportion of patients who achieved an Investigator Global Assessment (IGA) score of 0/1 as observed from OLE baseline to 2 years. Safety was also evaluated. Results A total of 180 patients were included in the 6 month to 5 years cohort; mean (±SD) age at OLE baseline was 3.9 (1.3) years with mean (SD) duration of AD of 3.5 (1.3) years. At OLE baseline, 29.4% of patients achieved EASI-75, improving to 85.1% at 52 weeks and 92.1% at 104 weeks. Similarly, 12.8% of patients achieved IGA 0/1 at OLE baseline, improving to 36.0% at Week 52 and 40.6% at Week 104. Total treatment-emergent adverse events (TEAEs) were observed in 87.8% of patients (intensity: mild 24.4%, moderate 52.2%, severe 11.1%). TEAEs assessed as related to dupilumab by the study investigators were reported in 18.3% of patients; the most prevalent were conjunctivitis (2.8%), allergic conjunctivitis (1.7%), nasopharyngitis (1.7%) and urticaria (1.7%). Serious TEAEs assessed as related to dupilumab by the study investigators were observed in 0.6% of patients. Conclusions Treatment with dupilumab for up to 2 years in young children with moderate-to-severe AD demonstrated efficacy outcomes, with sustained improvement in clinical signs reported in a large proportion of patients. Results are consistent with the known safety profile for dupilumab. [ABSTRACT FROM AUTHOR]

Introduction/Background Patients with atopic dermatitis (AD) have an increased risk of cutaneous, extracutaneous, and systemic infections with a considerable associated cost burden. Certain treatments used to manage AD, such as immunosuppressants and Janus kinase inhibitors, can increase the risk of infection. Data from the LIBERTY AD open-label extension study (OLE; NCT01949311) indicate that continuous dupilumab treatment for up to 4 years in adults with moderate-to-severe AD is not associated with an increased risk of overall systemic or cutaneous infections.1 Objectives To report exposure-adjusted incidence rates (EAIR) of infections in adults with moderate-to-severe AD treated with dupilumab for up to 5 years. Methods The OLE was a phase 3, multicenter, open-label extension trial that enrolled adults with moderate-to-severe AD who had participated in any dupilumab parent study (phase 1–3). During the OLE, patients were treated with 300mg dupilumab weekly (qw). 226 patients transitioned to 300mg every 2 weeks starting from Week 108 to align with approved dosage. Concomitant topical treatments for AD were permitted. The EAIR (patients with ≥1 event/100 patient-years [nP/100PY]) was calculated for treatment-emergent infections (Medical Dictionary for Regulatory Activities [MedDRA] System Organ Class [SOC] infections and infestations) and skin infections for the overall study population (N=2,677). Skin infections were defined as adjudicated non-herpetic skin infections from the SOC infections and infestations plus, conservatively, all MedDRA Preferred Terms (PT) in MedDRA High Level Term herpes viral infections. Because the OLE lacked a control arm, infection data from adults with moderate-to-severe AD receiving placebo qw + topical corticosteroids (TCS) in the 1-year LIBERTY AD CHRONOS trial (NCT02260986; n=315) are included for comparison. Data are presented as observed. Results From the 2,677 patients enrolled, 2,207/557/334 completed treatment up to Week 52/148/260. The most common reasons for study withdrawal during the OLE were dupilumab approval and commercialization (810/1,380 patients; 58.7% of withdrawals) and patient withdrawal (248/1,380 [18.0%]). Treatment-emergent adverse events led to permanent discontinuation in 101 (3.8%) patients. The EAIR of patients with ≥1 treatment-emergent infection was lower in this OLE vs the placebo qw + TCS arm of the 1-year CHRONOS trial (70.7 vs 107.0 nP/100PY). Over this 5-year OLE, 50 patients (0.9 nP/100PY) had ≥1 serious infection, 53 (0.9 nP/100PY) had ≥1 severe infection, and 20 (0.3 nP/100PY) experienced ≥1 infection resulting in permanent treatment discontinuation. Skin infections were reported in 535 patients (11.0 nP/100PY), comprising non-herpetic skin infections (249 patients; 4.6 nP/100 PY) and herpes viral infections (343 patients; 6.6 nP/100 PY). The EAIR of skin infections decreased throughout the OLE (1 year: 17.2 nP/100 PY; 3 years: 11.9 nP/100 PY; 5 years: 11.0 nP/100 PY) and was lower than the CHRONOS placebo qw + TCS arm (29.5 nP/100 PY). The most common PTs (≥5.0 nP/100PY) from the SOC infections and infestations were nasopharyngitis (774 patients; 17.6 nP/100PY), upper respiratory tract infection (365 patients; 7.0 nP/100PY), and conjunctivitis (277 patients; 5.2 nP/100PY; representing conjunctivitis of unspecified or undetermined etiology, including non-infectious cases). Conjunctivitis was the most common infection PT leading to treatment discontinuation (10 patients; 0.2 nP/100PY). The EAIR of serious infections remained stable during the OLE (1 year: 0.8 nP/100PY; 3 years: 0.9 nP/100PY; 5 years: 0.9 nP/100PY). Conclusions Long-term dupilumab treatment in adults with moderate-to-severe AD does not increase risk of systemic or cutaneous infections. Rates of treatment-emergent infections, including skin infections, in the OLE for up to 5 years were low, compared with patients receiving placebo + TCS in a 1-year study. Serious infection rates remained low and stable over the 5-year OLE. This report reinforces the known long-term safety profile of dupilumab from an infection perspective. [ABSTRACT FROM AUTHOR]

Introduction/Background The SCORing Atopic Dermatitis (SCORAD) index is a validated clinician-reported measurement used to assess the extent and intensity of atopic dermatitis (AD). Multiple severity threshold bands have been published to translate the SCORAD's numeric scoring index into clinically meaningful categories, most of which were developed using small patient numbers in clinical practice. Further analyses using larger patient numbers from other clinical settings may provide additional insights into AD severity and outcomes. Objective To report an analysis of SCORAD severity bands using a large, pooled dataset of global, randomized, placebo-controlled clinical trials of dupilumab in adults with moderate-to-severe AD. Methods Data were collected during 2013–2016 from 5 double-blind, randomized, placebo-controlled trials of dupilumab in adults with moderate-to-severe AD (NCT01859988, NCT02277743, NCT02277769, NCT02260986, NCT02755649). Total SCORAD (range 0–103) data from all patients receiving dupilumab and placebo were pooled from all visits, excluding first visit. SCORAD values were anchored to the Investigator's Global Assessment (IGA) and designated into 5 severity categories: Clear, Almost Clear, Mild, Moderate, and Severe. Spearman's rank correlations were calculated between total SCORAD and IGA values. For each integer value of SCORAD, the following were calculated to determine potential threshold bands: means analyzed with spline regression (which accounts for potential non-linear relationships between anchor and outcome, and provides a broader range of potential thresholds); medians and modes; frequencies (where the threshold of the first severity band was set to 0 and each successive severity band was set at the value of the outcome measure where the maximum anchor frequency changes category); and results of previous analyses by Chopra et al. (Br J Dermatol. 2017;177:1316-21) and Kunz et al. (Dermatology. 1997;195:10-19), modified to incorporate 5 severity categories. Thresholds for body surface area (BSA, 0–100) and total SCORAD subscales (observed SCORAD [oSCORAD, 0–83], Pruritus Visual Analog [VAS, 0–10], and Sleep Loss VAS [0–10]) by medians were also evaluated. Goodness-of-fit and concordance between bands and anchors were assessed using R2 and quadratic weighted kappa (κ)-coefficients. Results Data from 31,367 visits from 2,822 adults with moderate-to-severe AD were used. The following banding thresholds were identified using the frequencies, medians, and modes: 0–4.9 (Clear), 5–17.9 (Almost Clear), 18–36.9 (Mild), 37–68.9 (Moderate), and 69–103 (Severe; R2: 0.997; κ: 0.831). Bands identified using the means were similar: 0–5.9 (Clear), 6–17.9 (Almost Clear), 18–36.9 (Mild), 37–77.9 (Moderate), 78–103 (Severe; R2: 0.999; κ: 0.815). Severity thresholds evaluated using modified results from Chopra et al. and Kunz et al. produced the following bands, respectively: 0–5.9 (Clear), 6–24.9 (Almost Clear), 25–49.9 (Mild), 50–77.9 (Moderate), and 78–103 (Severe; R2: 0.998; κ: 0.742); and 0–9.9 (Clear), 10–28.9 (Almost Clear), 29–39.9 (Mild), 40–77.9 (Moderate), and 78–103 (Severe; R2: 0.998; κ: 0.769). Analysis of BSA and SCORAD subscales by medians produced the following bands: BSA – 0–0.09 (Clear), 1–4.9 (Almost Clear), 5–22.9 (Mild), 23–79.9 (Moderate), and 80–100 (Severe); oSCORAD - 0–4.9 (Clear), 5–15.9 (Almost Clear), 16–31.9 (Mild), 32–58.9 (Moderate), and 59–83 (Severe); Pruritus VAS - 0–1.9 (None), 2–4.9 (Mild), 5–8.9 (Moderate/Severe), and 9–10 (Very Severe); and Sleep Loss VAS - 0–0.9 (None), 1–3.9 (Mild), 4–8.9 (Moderate), and 9–10 (Severe/Very Severe). Conclusions The SCORAD threshold bands developed in this anchor-based analysis utilized a large, global, diverse data set of adult patients with AD from clinical trials and used spline regressions as a novel methodology. These potential severity bands may enhance the understanding of AD severity and disease stratification. [ABSTRACT FROM AUTHOR]

Introduction/Background Seasonal trends in atopic dermatitis (AD)-related healthcare visits vary by geographical location and climate. Changes in temperature, moisture, and allergens contribute to disease fluctuation activities throughout the year. The global, placebo-controlled, 1-year LIBERTY AD CHRONOS study (NCT02260986) offers the opportunity to evaluate AD seasonality and the impact of dupilumab on moderate-to-severe AD in adults regardless of season. Objectives To identify seasonal trends in patient-reported AD severity and frequency of symptoms, and to report the effect of dupilumab treatment in adults with moderate-to-severe AD across seasons. Methods CHRONOS was a randomized, double-blind, phase 3 trial of adults with moderate-to-severe AD.1 Patients were treated with dupilumab 300 mg every week (qw), every two weeks (q2w), or placebo qw, all with concomitant topical corticosteroids (TCS). In this post hoc analysis, the proportion of patients per severity category of Patient-Oriented Eczema Measure (POEM) score (range 0–28) by month was compared between patients receiving dupilumab 300 mg q2w + TCS (n = 79) or placebo qw + TCS (n = 234) for 1 year across 10 countries in the Northern Hemisphere. Improvement in AD was determined as an increase in proportion of patients with mild and clear POEM scores (≤7). Meteorological seasons were defined as winter (December 1 – February 28/29), spring (March 1 – May 31), summer (June 1 – August 31), and fall (September 1 – November 30). Sensitivity analyses confirmed that season of enrollment was balanced across treatment arms and disease seasonality was independent of treatment length. P values are based on Chi-Square tests or Monte Carlo simulations of the Exact Test, based on sample size. All P values are nominal, and no adjustments have been made for multiple testing. Data are presented as observed. Results The proportion of patients in both treatment arms with mild and clear POEM scores (≤7) was lowest in spring months (March: 13% vs 24%; April: 10% vs 23%; May: 20% vs 44%; placebo vs dupilumab). The proportion of patients with mild and clear POEM scores was increased through summer (June: 21% vs 54%; July: 24% vs 58%; August: 29% vs 53%; placebo vs dupilumab) and fall (September: 27% vs 62%; October: 23% vs 58%; November: 21% vs 63%; placebo vs dupilumab), before beginning to decline in winter (December: 21% vs 56%; January: 16% vs 46%; February: 15% vs 41%; placebo vs dupilumab). Overall, POEM scores indicated significantly better outcomes for patients receiving dupilumab treatment vs placebo throughout the year (overall P < 0.01 for all 12 months). Conclusions Across the Northern Hemisphere, patient-reported disease severity in adults with moderate-to-severe AD was greatest in the spring months. Adults with moderate-to-severe AD receiving dupilumab treatment reported improvement in frequency of disease symptoms across all seasons compared to patients receiving placebo treatment. [ABSTRACT FROM AUTHOR]

Introduction Itch is the most bothersome symptom for patients with atopic dermatitis (AD), and has a significant negative impact on health-related quality of life. Rapid onset of pruritus relief with sustained efficacy is a key outcome for AD therapies. In ADORING 1 and 2, two identical pivotal phase 3, double-blind, vehicle-controlled trials, tapinarof cream 1% once daily (QD) demonstrated efficacy and was well tolerated in adults and children down to 2 years of age with AD. Objective Here, we evaluate time to onset of itch relief in the pivotal phase 3 trials. Methods In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic DermatitisTM score of ≥3 (moderate or severe), an Eczema Area and Severity Index score of ≥6, and body surface area involvement of 5–35% were randomized 2:1 to tapinarof cream or vehicle QD for 8 weeks. Itch relief was assessed by changes in Peak Pruritus Numerical Rating Scale (PP-NRS) score, daily and by visit, from baseline through Week 8. PP-NRS considers itch over the past 24 hours; lower scores indicate less pruritus. Results 407 and 406 patients were randomized in ADORING 1 and 2. At baseline, mean PP-NRS scores were 6.7 and 6.8 in both trials, respectively. For daily evaluations of itch from baseline, greater reductions in mean PP-NRS scores for tapinarof versus vehicle were observed as early as Day 1, 24 hours after initial application in ADORING 1 (–1.2 vs –0.9), and Day 2 in ADORING 2 (–1.6 vs –1.4). Daily itch improvements continued through Week 8 in both trials. Statistically significant reductions in mean weekly PP-NRS scores occurred as early as Week 1 (earliest assessment) with tapinarof versus vehicle (–2.0 vs –1.2 [ P <0.0001]) and (–2.0 vs –1.3 [ P =0.0010]) in ADORING 1 and 2, respectively. Significantly greater reductions in mean PP-NRS scores with tapinarof versus vehicle were seen for all visits through Week 8 (–4.1 vs –2.6 and –4.1 vs –2.4 [both P<0.0001]). Conclusions Tapinarof cream 1% QD demonstrated rapid, significant, and clinically meaningful pruritus relief from 24 hours after initial application, with improvements increasing through Week 8 in both trials in adults and children down to 2 years with AD. [ABSTRACT FROM AUTHOR]

Background: Baricitinib demonstrated efficacy in treating adults with moderate‐to‐severe atopic dermatitis (AD) in Phase 3 clinical trials. Objective: To examine long‐term efficacy of baricitinib combined with topical corticosteroids (TCS) in adult patients from a Phase 3 study, BREEZE‐AD7 (NCT03733301), enrolled in ongoing extension study, BREEZE‐AD3 (NCT03334435). Methods: Upon BREEZE‐AD7 completion, responders or partial responders (RPR [vIGA‐AD™ ≤2]) receiving baricitinib 2‐mg or 4‐mg + TCS maintained their original treatment doses in BREEZE‐AD3. Nonresponders (NR; vIGA‐AD 3,4) receiving baricitinib 2‐mg were rerandomized 1:1 to baricitinib 2‐mg or 4‐mg; NR receiving baricitinib 4‐mg remained on same dose. Integrated data from all patients (RPR + NR = baricitinib 4‐mg intent‐to‐treat [ITT] cohort) receiving continuous baricitinib 4‐mg in BREEZE‐AD7 through BREEZE‐AD3 were analysed, along with baricitinib 4‐mg or 2‐mg RPR cohorts. Primary endpoint was proportion of patients with vIGA‐AD (0,1) at Weeks 16, 36 and 52 (Weeks 32, 52 and 68 of continuous therapy). Additional outcomes included improvement in EASI75 and Itch NRS (up to Week 32). Missing data were imputed by last observation carried forward. Results: In baricitinib 4‐mg ITT cohort (N = 102), proportions of patients achieving vIGA‐AD (0,1) at Week 32, Week 52, and Week 68 were 21.6%, 26.5% and 23.5%; EASI75 were 46.1%, 40.2% and 43.1%, respectively. Itch NRS ≥4‐point improvement (Itch ≥4) were 47.3% at Week 16 and 40.6% at Week 32. In baricitinib 4‐mg RPR cohort (N = 63), proportions of patients achieving vIGA‐AD (0,1) at Week 32, Week 52 and Week 68 were 31.7%, 33.3% 34.9%, respectively; EASI75 were 57.1%, 49.2% and 49.2%, respectively. Itch ≥4 were 53.6% at Week 16 and 46.4% at Week 32. Corresponding proportions for baricitinib 2‐mg RPR cohort (N = 53) for vIGA‐AD (0,1) were 39.6%, 45.3% and 30.2%; EASI75 were 77.4%, 69.8% and 58.5%, respectively. Itch ≥4 were 56.3% at Week 16 and 47.9% at Week 32. Conclusion: Baricitinib 4‐mg and 2‐mg combined with TCS maintained clinically meaningful sustained efficacy over 68 weeks of continuous treatment. [ABSTRACT FROM AUTHOR]

Background: Baricitinib, an oral, selective Janus kinase 1/2 inhibitor, demonstrated long-term efficacy in moderate-to-severe atopic dermatitis in an ongoing double-blind, phase III, long-term extension study, BREEZE-AD3 (NCT03334435). Objectives: To evaluate the efficacy and safety of downtitration and treatment withdrawal in a substudy of BREEZE-AD3. Methods: The substudy included patients (N = 526) treated with baricitinib 4 mg or 2 mg at entry into BREEZE-AD3 who achieved a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD®) scale score of 0 (clear), 1 (almost clear) or 2 (mild) at week 52. Patients treated with baricitinib 4 mg were rerandomized to baricitinib 4 mg (continuous dosing), baricitinib 2 mg (downtitration) or placebo (treatment withdrawal, 4-mg cohort), and patients treated with baricitinib 2 mg were rerandomized to baricitinib 2 mg (continuous dosing), baricitinib 1 mg (downtitration), or placebo (treatment withdrawal, 2-mg cohort). After 16 weeks, we assessed the proportion of patients with vIGA-AD® 0/1, vIGA-AD® 0/1/2, vIGA-AD® ≥ 3 (loss of response; criterion to readminister the original baricitinib dose) and for patients who were readministered the original baricitinib dose, we assessed the proportion of patients who recaptured vIGA-AD® 0/1/2 within 16 weeks of treatment readministration (patients in the continuous dosing maintained the same dose). Results: For the continuous dosing, downtitration, and treatment withdrawal groups 51%, 45% and 30% of patients in the 4-mg cohort achieved vIGA-AD® 0/1 and 87%, 61% and 50% of patients achieved vIGA-AD® 0/1/2, respectively. For the 2-mg cohort, the respective proportions of patients were 48%, 42% and 25% for vIGA-AD® 0/1 and 92%, 71% and 45% for vIGA-AD® 0/1/2. The respective proportions of patients with vIGA-AD® ≥ 3 were 39%, 49% and 56% in the 4-mg cohort and 41%, 41% and 64% in the 2-mg cohort. Of those who were readministered the original baricitinib dose, the proportions of patients who recaptured vIGA-AD® 0/1/2 among the continuous dosing, downtitration, and treatment withdrawal groups were 80%, 85% and 88% in the 4-mg cohort and 90%, 56% and 86% in the 2-mg cohort, respectively. Conclusions: Baricitinib allows flexibility for patients to downtitrate or stop treatment. For patients who downtitrated treatment, the majority maintained efficacy through 16 weeks. Most patients who lost efficacy with downtitration or treatment withdrawal achieved clinically relevant efficacy upon readministration of their original dose. Baricitinib, an oral, selective Janus kinase (JAK)1/2 inhibitor, demonstrated long-term efficacy in moderate-to-severe atopic dermatitis (AD) in an ongoing, double-blind, Phase 3, long-term extension study, BREEZE-AD3 (NCT03334435). Baricitinib allows flexibility for patients to downtitrate or stop treatment. For patients who downtitrated treatment, the majority maintained efficacy through 16 weeks. Most patients who lost efficacy with downtitration or treatment withdrawal achieved clinically relevant efficacy upon readministration of their original dose. [ABSTRACT FROM AUTHOR]

OX40 is crucial for T-cell differentiation and memory induction. The anti-OX40 antibody, rocatinlimab inhibits the OX40 pathway. We evaluated the efficacy and safety of rocatinlimab in adults with moderate-to-severe atopic dermatitis. This multicentre, double-blind, placebo-controlled phase 2b study was done at 65 secondary and tertiary sites in the USA, Canada, Japan, and Germany. Eligible patients were adults (aged 18 years or older) with confirmed atopic dermatitis (American Academy of Dermatology Consensus Criteria or local diagnostic criteria) with moderate-to-severe disease activity, as defined by an Eczema Area and Severity Index (EASI) score of 16 or more, validated Investigator's Global Assessment for Atopic Dermatitis score of 3 (moderate) or 4 (severe), and affected body surface area 10% or higher at both screening and baseline, with documented history (within 1 year) of inadequate response to topical medications or if topical treatments were medically inadvisable. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous rocatinlimab every 4 weeks (150 mg or 600 mg) or every 2 weeks (300 mg or 600 mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up. Percentage change from baseline in EASI score was assessed as the primary endpoint at week 16 and during the active extension and follow-up in all randomly assigned patients exposed to study drug with a post-baseline EASI score at week 16 or earlier according to the group they were randomly assigned to. Safety was assessed in all randomly assigned patients exposed to study drug; patients were analysed according to the group they were randomly assigned to. The study is registered with ClinicalTrials.gov , NCT03703102. Between Oct 22, 2018, and Oct 21, 2019, 274 patients (114 [42%] women, 160 [58%] men; mean age 38·0 years [SD 14·5]) were randomly assigned to one of the rocatinlimab groups (217 [79%] patients) or to the placebo group (57 [21%] patients). Compared with placebo (−15·0 [95% CI −28·6 to −1·4]), significant least-squares mean percent reductions in EASI score at week 16 were observed in all rocatinlimab groups (rocatinlimab 150 mg every 4 weeks −48·3 [−62·2 to −34·0], p=0·0003; rocatinlimab 600 mg every 4 weeks −49·7 [−64·3 to −35·2], p=0·0002; rocatinlimab 300 mg every 2 weeks −61·1 [−75·2 to −47·0], p<0·0001; and rocatinlimab 600 mg every 2 weeks −57·4 [−71·3 to −43·4], p<0·0001). The most common adverse events during the double-blind period in patients receiving rocatinlimab (adverse events ≥5% of patients in the total rocatinlimab group and more common than the placebo group) were pyrexia (36 [17%] patients), nasopharyngitis (30 [14%] patients), chills (24 [11%] patients), headache (19 [9%] patients), aphthous ulcer (15 [7%] patients), and nausea (13 [6%] patients). There were no deaths. Patients treated with rocatinlimab had progressive improvements in atopic dermatitis, which was maintained in most patients after treatment discontinuation. Treatment was well tolerated. Kyowa Kirin. [ABSTRACT FROM AUTHOR]

To address the need for long‐term efficacy and patient‐reported outcomes (PROs) data for patients with atopic dermatitis (AD) treated with baricitinib 2 mg, a study was conducted to evaluate the efficacy of baricitinib 2 mg in adult patients with moderate‐to‐severe AD. Data presented here provided efficacy and outcomes data for patients treated for 52 weeks. Patients who participated in the originating study, BREEZE‐AD5 (NCT03435081), and met additional eligibility criteria could enroll in the multicenter, open‐label, Phase 3, long‐term extension study BREEZE‐AD6 (NCT03559270). Patients received baricitinib 2 mg for the duration of BREEZE‐AD6. In BREEZE‐AD6, the proportion of patients who achieved a 75% improvement in the Eczema Area and Severity Index (EASI75) and validated Investigator Global Assessment for AD (vIGA‐AD™) of 0 (clear) or 1 (almost clear) were assessed through 52 weeks, in addition to several PROs. At week 52, the proportion of patients treated with baricitinib 2 mg daily achieving EASI75 was 48.6% (70/144), and 31.3% (45/144) of patients achieved a vIGA‐AD score of 0 or 1 (clear or almost clear). Improvements in PROs such as SCORing Atopic Dermatitis (SCORAD, itch and sleep) scores, Dermatology Life Quality Index (DLQI) total score, and DLQI ≤5 response were observed, and these responses were sustained through 52 weeks. Long‐term efficacy of baricitinib in patients with AD was demonstrated by both clinician and patient‐reported outcome measures. [ABSTRACT FROM AUTHOR]

Background: Tralokinumab is a fully human monoclonal antibody that neutralizes the activity of interleukin‐13, a key pathogenic driver of atopic dermatitis (AD). Clinical trials including adults with moderate‐to‐severe AD, of up to 52 weeks' duration, showed tralokinumab was efficacious and well tolerated. Objectives: To characterize the safety profile of tralokinumab for the treatment of moderate‐to‐severe AD. Methods: Safety and laboratory measures were assessed in pooled analyses of phase II and III placebo‐controlled clinical trials of tralokinumab in moderate‐to‐severe AD (NCT02347176, NCT03562377, NCT03131648, NCT03160885, NCT03363854). Results: In total, 2285 patients were randomized in the initial treatment periods up to 16 weeks (1605 tralokinumab, 680 placebo). The frequencies of any adverse event (AE) were 65·7% for tralokinumab and 67·2% for placebo. The respective rates were 640 and 678 events per 100 patient‐years of exposure (ep100PYE); rate ratio 1·0, 95% confidence interval (CI) 0·9–1·1. Serious AEs occurred in 2·1% of patients with tralokinumab and 2·8% with placebo (7·4 and 11·9 ep100PYE; rate ratio 0·7, 95% CI 0·4–1·2). The most common AEs occurring at a higher frequency and rate with tralokinumab vs. placebo were: viral upper respiratory tract infection (15·7% vs. 12·2%; 65·1 vs. 53·5 ep100PYE); upper respiratory tract infection (5·6% vs. 4·8%; 20·8 vs. 18·5 ep100PYE); conjunctivitis (5·4% vs. 1·9%; 21·0 vs. 6·9 ep100PYE); and injection‐site reaction (3·5% vs. 0·3%; 22·9 vs. 4·0 ep100PYE). Some events in safety areas of interest occurred at a lower frequency and rate with tralokinumab vs. placebo: skin infections requiring systemic treatment (2·6% vs. 5·5%; 9·7 vs. 22·8 ep100PYE), eczema herpeticum (0·3% vs. 1·5%; 1·2 vs. 5·2 ep100PYE), opportunistic infections (3·4% vs. 4·9%; 13·0 vs. 21·3 ep100PYE) and serious infections (0·4% vs. 1·1%; 1·3 vs. 3·7 ep100PYE). AEs did not increase with continued maintenance and open‐label treatment, including rates of common or serious AEs and AEs leading to study drug discontinuation. No clinically meaningful changes in mean laboratory measures were observed with treatment up to 1 year. Conclusions: Across the AD population pool from five clinical trials, tralokinumab was well tolerated, with consistent safety findings during treatment of patients with moderate‐to‐severe AD. The safety profile during prolonged tralokinumab treatment was consistent with that during the initial treatment period; the frequency of events did not increase over time. What is already known about this topic?Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin‐13, a key cytokine driving skin inflammation and epidermal barrier dysfunction in atopic dermatitis (AD).In clinical trials in moderate‐to‐severe AD, tralokinumab provided significant and early improvements in the extent and severity of AD and was well tolerated, with an overall safety profile comparable with placebo over 52 weeks. What does this study add?We report the frequency and rate of adverse events (AEs) from pooled observations of over 2000 patients from five phase II and phase III placebo‐controlled clinical trials of tralokinumab in moderate‐to‐severe AD.During initial treatment up to 16 weeks, the frequencies of any AE and of serious AEs were similar for tralokinumab and placebo. AE rates did not increase with continued treatment up to 52 weeks.Common AEs occurring more frequently with tralokinumab vs. placebo were viral and upper respiratory tract infection, conjunctivitis and injection‐site reaction. Some events occurred at a lower frequency and rate with tralokinumab vs. placebo, such as skin infections requiring systemic treatment, eczema herpeticum and opportunistic and serious infections.No clinically meaningful changes in mean laboratory measures were observed. [ABSTRACT FROM AUTHOR]

Introduction: Three patient-reported outcome (PRO) questionnaires—Worst Pruritus Numerical Rating Scale (WP-NRS), Atopic Dermatitis Symptom Scale (ADerm-SS), and Atopic Dermatitis Impact Scale (ADerm-IS)—were developed to assess the symptoms and impacts of atopic dermatitis (AD). Severity strata for these PROs are needed to aid in their interpretation. Methods: Using data from a global, randomized, double-blind, placebo-controlled, phase 3 clinical trial (NCT03568318) of patients with moderate–severe AD (age ≥ 12 years), equipercentile linking analyses were conducted to define severity strata applying the Patient Global Impression of Severity as an anchor. Analyses were conducted separately for adults and adolescents, and then harmonized between the two age groups. Results: The sample included 769 adults and 113 adolescents. For the WP-NRS, 0 was associated with absent, 1–2 with minimal, 3 with mild, 4–7 with moderate, and 8–10 with severe. For the ADerm-SS Skin Pain, 0 was associated with absent, 1 with minimal, 2 with mild, 3–6 with moderate, and 7–10 with severe. For ADerm-SS 7-Item Total Symptom Score (TSS-7), 0–1 was associated with absent, 2–11 with minimal, 12–22 with mild, 23–47 with moderate, and 48–70 with severe. For ADerm-IS Sleep, 0 was associated with absent, 1–3 with minimal, 4–6 with mild, 7–20 with moderate, and 21–30 with severe. For ADerm-IS Daily Activities, 0 was associated with absent, 1–2 with minimal, 3–7 with mild, 8–25 with moderate, and 26–40 with severe. For ADerm-IS Emotional State, 0 was associated with absent, 1–2 with minimal, 3–8 with mild, 9–22 with moderate, and 23–30 with severe. Conclusions: These severity strata provide score interpretations of the WP-NRS, ADerm-SS, and ADerm-IS, translating these scores to simple and intuitive outcomes, which can inform clinical studies and clinical practice. Trial Registration Number: NCT03568318. [ABSTRACT FROM AUTHOR]

Background: The validated Investigator Global Assessment for Atopic Dermatitis (vIGA‐AD™) is a standardized severity assessment for use in clinical trials and registries for atopic dermatitis (AD). Objectives: To investigate the reliability, validity, responsiveness and within‐patient meaningful change of the vIGA‐AD. Methods: Data were analysed from adult patients with moderate‐to‐severe AD in the BREEZE‐AD1 (N = 624 patients; NCT03334396), BREEZE‐AD2 (N = 615; NCT03334422) and BREEZE‐AD5 (N = 440; NCT03435081) phase III baricitinib clinical studies. Results: Across studies, test–retest reliability for stable patients showed moderate‐to‐good agreement [range of Kappa values for Patient Global Impression of Severity–Atopic Dermatitis (PGI‐S‐AD), 0·516–0·639; for Eczema Area and Severity Index (EASI), 0·658–0·778]. Moderate‐to‐large correlations between vIGA‐AD and EASI or body surface area (range at baseline, 0·497–0·736; Week 16, 0·716–0·893) supported convergent validity. Known‐groups validity was demonstrated vs. EASI and PGI‐S‐AD (vIGA‐AD for severe vs. moderate EASI categories at baseline, P < 0·001). Responsiveness was demonstrated vs. EASI (P < 0·001 for much improved vs. improved and improved vs. stable). Anchor‐ and distribution‐based methods supported a vIGA‐AD change of –1·0 as clinically meaningful. These findings are limited to populations defined by the studies' inclusion and exclusion criteria. Conclusions: The vIGA‐AD demonstrated sufficient reliability, validity, responsiveness and interpretation standards for use in clinical trials. What is already known about this topic?A description of the development of the validated Investigator Global Assessment for Atopic Dermatitis (vIGA‐AD™) has been published previously. What does this study add?The current study validates the vIGA‐AD by demonstrating appropriate test–retest reliability, convergent validity, known‐groups validity and responsiveness across three baricitinib clinical studies.In addition, a 1‐point change was identified as a clinically meaningful patient‐perceived change minimal clinically important difference in the vIGA‐AD. What are the clinical implications of the work?The vIGA‐AD is a measure for investigator assessment of atopic dermatitis suitable for use in clinical research. [ABSTRACT FROM AUTHOR]

Introduction Roflumilast is a selective, highly potent phosphodiesterase 4 inhibitor under investigation as a nonsteroidal, once-daily cream for treatment of atopic dermatitis (AD). Methods We present pooled results from two identical phase 3 randomized controlled trials (INTEGUMENT-1: NCT04773587; INTEGUMENT-2: NCT04773600) of roflumilast cream 0.15%. Patients aged ≥6 years with mild to moderate AD were randomized 2:1 to apply roflumilast (n=884) or vehicle (n=453) cream once-daily for 4 weeks. The primary endpoint was validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success (Clear/Almost Clear vIGA-AD plus ≥2-grade improvement from baseline) at Week 4. Patient-reported outcomes (PROs) were evaluated using the Worst Itch-Numeric Rating Scale (WI-NRS), SCORing AD (SCORAD), Patient-Oriented Eczema Measure, Dermatology Life Quality Index/Children's Dermatology Life Quality Index, and the Dermatitis Family Impact questionnaire. Safety and tolerability were also evaluated. Results At Week 4, more roflumilast- than vehicle-treated patients achieved vIGA-AD Success (31.3% vs. 14.1%, P<0.0001), WI-NRS Success (≥4-point improvement on WI-NRS in patients aged ≥12 years with baseline WI-NRS ≥4; 31.9% vs. 16.6%, P<0.0001); and WI-NRS of 0/1 (in patients with baseline WI-NRS ≥2; 28.8% vs 18.5%, P=0.0087). At Week 4, roflumilast-treated patients improved more than vehicle-treated on the pruritus and sleep components of SCORAD (least squares mean percentage change −48.2% vs. −27.8%; [P<0.0001] and −47.9% vs. −22.9% [P<0.05], respectively). Differences favoring roflumilast were also seen for other secondary endpoints, including quality of life of the patient and family. Safety and local tolerability were favorable. Conclusion Once-daily, nonsteroidal roflumilast cream 0.15% improved PROs in patients with AD. [ABSTRACT FROM AUTHOR]

Background Roflumilast, a highly potent phosphodiesterase-4 inhibitor, is being investigated as a non-steroidal, once-daily cream for atopic dermatitis (AD). Methods INTEGUMENT-OLE (NCT04804605) was an open-label 52-week safety trial. Patients (N=658) with mild to moderate AD who completed a 4-week randomized vehicle-controlled phase 3 trial of roflumilast cream continued or switched to once-daily roflumilast cream 0.15% in this open-label extension trial. Starting at Week 4, patients achieving Validated Investigator Global Assessment for AD (vIGA-AD) score of 0 (Clear) switched to twice-weekly (BIW) maintenance dosing. The primary endpoint was safety; secondary endpoints included vIGA-AD, Worst Itch-Numeric Rating Scale (WI-NRS), and Eczema Area and Severity Index (EASI). "Disease control" was defined as duration of vIGA-AD=0/1 on BIW dosing following achievement of vIGA-AD=0. Results With cumulative treatment up to 56 weeks, 36.7% of patients reported treatment-emergent adverse events (AEs); most were mild to moderate in severity. Overall, 4.7% of patients had AEs deemed treatment-related and 3.0% discontinued due to AEs. The most common AEs (>2%) were COVID-19, upper respiratory tract infection, nasopharyngitis, and headache. At Week 52, 55.7%, 61.1%, and 53.6% of patients achieved vIGA-AD=0/1 (Clear/Almost Clear), ≥75% reduction in EASI, and ≥4-point reduction in WI-NRS (among patients aged ≥12 years with baseline WI-NRS ≥4), respectively. Of the 130 (19.8%) patients who achieved disease control, 50% maintained "disease control" for at least 281 days. Conclusion Treatment with roflumilast cream 0.15% demonstrated long-term safety in patients with AD consistent with parent trials and durable efficacy through 52 weeks, including patients who switched to BIW dosing. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Findings: 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.Interpretation: 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.Funding: Sanofi and Regeneron Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Introduction/Background Dupilumab has previously shown overall efficacy in treating atopic hand and foot dermatitis. Objective To report the effect of dupilumab treatment on individual signs of atopic hand and foot dermatitis. Methods: The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients aged =12 years with moderate-to-severe (Investigator's Global Assessment [IGA] score of 3/4) atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg every 2 weeks (q2w) in adults; 200/300 mg q2w in adolescents, or placebo for 16 weeks. This analysis presents the proportion of patients reporting absent, mild, moderate, or severe erythema, scaling/flaking, lichenification, vesiculation/erosion, edema, and fissures, assessed by the modified total lesion sign score (mTLSS) in hands and feet. Results: At baseline, most patients had scores of moderate or severe signs on their hands. Of the 133 patients enrolled, over 65% of patients treated with dupilumab (n = 67) achieved an absent or mild score by Week 16 in each of the signs/symptoms assessed. Proportion of patients with absent or mild hand scores increased from baseline to Week 16 in erythema (9% vs 71.6%), scaling/flaking (16.4% vs 74.7%), lichenification (4.5% vs 65.6%), vesiculation/erosion (43.3% vs 89.6%), edema (44.7% vs 86.6%), and fissures (23.9% vs 83.5%). Proportion of patients with absent or mild foot scores increased from baseline to Week 16 in erythema (56.7% vs 80.6%), scaling/flaking (56.7% vs 82.1%), lichenification (53.8% vs 82.1%), vesiculation/erosion (76.1% vs 86.6%), edema (76.1% vs 88.1%), and fissures (77.6% vs 86.6%). Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis. Conclusions: Dupilumab treatment in patients improves signs of hand and foot dermatitis, including erythema, scaling/flaking, lichenification, vesiculation/erosion, edema, and fissures. [ABSTRACT FROM AUTHOR]

Introduction/Background As symptoms of atopic dermatitis (AD) can wax and wane over time, disease control is better represented by consistency of response over a long treatment duration rather than at a single time point. Objective To evaluate the proportion of pediatric patients achieving and maintaining mild or no itch (defined by a SCORing Atopic Dermatitis (SCORAD) itch visual analog scale (VAS; 0-10 over last 3 days) score of lower than 4) across 5 visits during a 52-week open label extension trial of dupilumab. Methods: Patients who previously participated in 16-week trials and were aged 0.5-5 years (LIBERTY AD PRESCHOOL; NCT03346434), 6-11 years (LIBERTY AD PEDs; NCT03345914), and 12-17 years (LIBERTY AD ADOL; NCT03054428), were subsequently enrolled in the phase 3, open-label extension trial, LIBERTY AD PED-OLE (NCT02612454). Patients were treated with 300 mg q4w or 200/300 mg q2w (body weight <60 or ≥60 kg, respectively). In this analysis, patients with a SCORAD itch VAS score of greater than 4 at OLE baseline, were assessed for the maintenance of SCORAD itch VAS lower than 4, at 5 timepoints: Weeks 4, 16, 28, 40, and 52. Results: In 763 patients, 400 patients with a SCORAD itch VAS score of greater than 4 were assessed. Mild or no itch was achieved in at least 4 of 5 timepoints in most patients aged 0.5-5 years (55/110; 50%), 6-11 years (76/148; 51%), and 12-17 years (73/142; 51%). Across these age groups, over 65% maintained this response for at least 3 of 5 timepoints. Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis. Conclusions: Most pediatric patients achieved improvement in itch, maintained during 1 year of treatment with dupilumab. Results were consistent for infants/preschoolers, children, and adolescents. [ABSTRACT FROM AUTHOR]

Background Dupilumab has shown efficacy in the treatment of atopic dermatitis (AD) in clinical trials, but there is a need for longterm data on patients starting dupilumab treatment for atopic dermatitis in a real-world setting. Methods: PROSE (NCT03428646) is an ongoing 5-year, prospective, observational study of patients aged ≥12 years who initiated commercially available dupilumab treatment for AD per country-specific prescribing information. Patients received a loading dose of dupilumab at baseline, without restrictions on post-baseline dosing changes or concomitant medication and were encouraged to stay in the study if they discontinued dupilumab. Data presented are descriptive, from a 3-year interim analysis. Results: 857 patients were enrolled. In these patients, mean (SD) age was 40.1 (17.9) years, AD duration 17.4 (16.2) years, and dupilumab treatment duration 23.1 (13.7) months (M). Mean (SE) baseline EASI total score was 16.2 (0.4), Pruritus Numerical Rating Scale (NRS) 7.1(0.1), Dermatology Life Quality Index (DLQI) 13.3 (0.3), and skin pain NRS 5.4 (0.1). 189 (22.1%) patients had withdrawn by data cut-off; the most common reasons for discontinuation were withdrawal of consent in 76 patients and loss to follow-up in 30. Mean (SE) EASI total score was 5.6 (0.4) at 3M, 2.9 (0.2) at 12M, 2.7 (0.4) at 24M, and 1.7 (0.3) at 36M. Mean (SE) change from baseline in Peak Pruritus NRS was -3.5 (0.2) at 3M, -4.2 (0.2) at 12M, -4.7 (0.2) at 24M, and -5.1 (0.3) at 36M. Mean (SE) change from baseline in DLQI was -7.4 (0.3) at 3M, -8.3 (0.7) at 12M, -9.2 (0.9) at 24M, and -8.8 (1.5) at 36M. Mean (SE) change from baseline in skin pain NRS was -3.3 (0.3) at 3M, -3.8 (0.2) at 12M, -4.0 (0.3) at 24M, and -4.6 (0.3) at 36M. Safety findings were consistent with the previously described safety profile of dupilumab. Conclusion: In this interim analysis of the PROSE registry, sustained disease control was observed in patients with moderate-to-severe AD for up to 3 years after initiating dupilumab treatment. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is a chronic, recurrent, inflammatory disease characterized by multiple skin manifestations and intense itching that can impact patient quality of life. The effect of upadacitinib (UPA) and dupilumab (DUP) was evaluated in a double-blind, double-dummy, head-to-head phase 3b clinical trial (Heads Up; NCT03738397) of adult patients (age: 18-75 years) with moderate-to-severe AD (Eczema Area and Severity Index [EASI] =16; body surface area =10%; validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) =3 at screening and baseline; Worst Pruritus Numerical Rating Scale [WP-NRS] =4 at baseline) randomized 1:1 to UPA 30 mg orally once-daily (N=348) or DUP 300 mg subcutaneous injection every two weeks after a 600 mg loading dose (N=344). Objective The effects of UPA and DUP on skin clearance and itch improvement are reported here. Methods: Skin clearance was assessed by EASI, with response defined as an improvement =75% (EASI75), =90% (EASI90), and 100% (EASI100) from baseline. Itch intensity was assessed daily by WP-NRS up to week 16, then at study visits up to week 24. Weekly WP-NRS scores were analyzed as a 7-day rolling average up to week 16, then at study visits through week 24. Daily WP-NRS scores were analyzed day-to-day through day 28. Mean percent improvement and the proportion of patients achieving clinically meaningful improvement (=4-point improvement from baseline) were evaluated. The proportion of patients achieving a state of no/minimal itch (defined as WP-NRS score of 0/1) was evaluated as a posthoc analysis. Results: EASI75/90/100 response rates were significantly greater with UPA versus DUP at week 16 (UPA = 72.4%/61.6%/28.4%, DUP = 62.6%/40.3%/7.9%; P<0.01 for all comparisons), with greater EASI75 and EASI90 rates observed with UPA as early as week 1 (nominal P<0.05). Mean percent improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 67.8%, DUP= 49.6%; P<0.001), with greater improvement observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater mean percent improvement with UPA versus DUP as early as day 2, the day after the first dose (UPA = 22.0%, DUP = 4.2%; nominal P<0.001). The proportion of patients that achieved clinically meaningful improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 56.1%, DUP = 36.4%; P<0.001), with greater proportions observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater proportion of patients achieved clinically meaningful improvement with UPA versus DUP as early as day 2 (UPA = 15.3%, DUP = 3.4%; nominal P<0.001). The proportion of patients that achieved a state of no/minimal itch based on weekly WP-NRS was greater with UPA versus DUP at week 16 (UPA = 35.5%, DUP = 16.2%; nominal P<0.001) and at week 1 (nominal P<0.001). Conclusions: Skin clearance and itch improvement were consistently better with UPA compared with DUP in adult patients with moderate-to-severe AD, with greater improvements observed as early as week 1 for skin clearance and the day following treatment for itch improvement. [ABSTRACT FROM AUTHOR]

Introduction Itch is the most bothersome symptom for patients with atopic dermatitis (AD), with a significant negative impact on health-related quality of life. Rapid onset of pruritus relief with sustained efficacy is a key outcome for AD therapies. In a phase 2 trial in adults and adolescents with moderate to severe AD, tapinarof cream 1% once daily (QD) demonstrated efficacy versus vehicle and was well tolerated. Objective Here, we evaluate time to onset of itch relief in the pivotal phase 3 trials with tapinarof cream 1% QD in the treatment of adults and children down to 2 years of age with AD. Materials and Methods In ADORING 1 and 2, two identical, double-blind, vehicle-controlled trials, patients were randomized 2:1 to tapinarof cream 1% or vehicle QD for 8 weeks. Patients with a Validated Investigator Global Assessment for Atopic DermatitisTM score of ≥3, an Eczema Area and Severity Index score of ≥6, and body surface area involvement of 5-35% were included. Efficacy endpoints that evaluated itch relief were mean changes in Peak Pruritus-Numerical Rating Scale (PP-NRS) score (daily and by visit [Weeks 1, 2, 4, and 8]) from baseline through Week 8. The PP-NRS considers a person's worst itch over the past 24 hours, assessed on an 11-point scale (0 indicates "no itch" and 10 is "worst imaginable itch"). Daily PP-NRS scores were recorded in diaries. Patients aged ≥12 years self-completed the PP-NRS, while caregivers completed it for children aged <12 years. Results: 407 and 406 patients were randomized in ADORING 1 and 2. At baseline, mean (standard deviation [SD]) PP-NRS scores were 6.7 (2.4) and 6.8 (2.3) in both trials, respectively. For daily evaluations of itch from baseline, greater reductions in PP-NRS scores (mean [SD]) for tapinarof versus vehicle were observed as early as Day 1, 24 hours after initial application, in ADORING 1 (-1.2 [2.2] vs -0.9 [2.0]) and Day 2 in ADORING 2 (-1.6 [2.4] vs -1.4 [2.1]). Improvements in daily PP-NRS scores (mean [SD]) with tapinarof versus vehicle continued through the first 2 weeks (Day 14; -3.0 [2.8] vs -2.0 [2.4] and -2.9 [2.7] vs -1.8 [2.6]), and through Week 8 of both trials. There were statistically significant and clinically meaningful reductions in mean weekly PP-NRS scores as early as Week 1, the first assessment, for patients treated with tapinarof compared with vehicle (-2.0 vs -1.2 [P<0.0001]) and (-2.0 vs -1.3 [P=0.0010]), in ADORING 1 and 2, respectively. Significantly greater reductions in mean PP-NRS scores with tapinarof versus vehicle were seen for all visits through Week 8 (-4.1 vs -2.6 and -4.1 vs -2.4 [both P<0.0001]), for both trials. Conclusions: Tapinarof cream 1% QD demonstrated rapid, clinically meaningful, and significant onset of pruritus relief as early as 24 hours after initial application compared with vehicle. Improvements in itch with tapinarof cream increased through Week 8 in both trials in adults and children down to 2 years with AD. [ABSTRACT FROM AUTHOR]

Baricitinib previously demonstrated improvements in itch and sleep disturbance versus placebo in adults with moderate-to-severe atopic dermatitis (AD). Examine if itch and sleep improvements are associated with better quality of life (QoL) and productivity in patients with AD. Data were drawn from BREEZE-AD5 (NCT03435081). Itch and sleep improvement at Week 16 were defined using ≥4-point improvements in the Itch Numeric Rating Scale and ≥1.5 decreases in the number of nighttime awakenings since baseline, respectively. Patients with and without improvements were compared on Dermatology Life Quality Index (DLQI) and Work Productivity and Activity Impairment-AD scores. Changes from baseline were analyzed using ANCOVA with last observation carried forward. Proportions were analyzed using logistic regression with non-responder imputation. Greater proportions of patients with versus without itch improvement indicated no impact of AD on QoL (37.7 vs. 1.8%). Patients with itch improvement had greater decreases in work time impaired (−29.3 vs. −5.6%). More patients with versus without sleep improvement reported no effect of AD on QoL (25.5 vs. 1.1%); patients with better sleep experienced larger reductions in work time spent impaired (−33.3 vs. −6.1%). Patients with AD who experienced itch and sleep improvement had significantly better QoL and productivity. [ABSTRACT FROM AUTHOR]

As atopic dermatitis (AD) is a chronic and potentially lifelong disease, it is important to determine the long-term safety of new treatments. Tralokinumab, which specifically targets interleukin-13, is approved in Europe, Canada and the United States for the treatment of adults with moderate-to-severe AD. During the initial 12–16 week placebo-controlled treatment period of Phase 2 and 3 trials, tralokinumab was well-tolerated with an overall frequency of adverse events (AEs) similar to the placebo. An ongoing open-label extension trial, ECZTEND (NCT03587805), is assessing the safety and efficacy of tralokinumab up to 5 years after parent trials (PT). To report an interim safety analysis of patients treated with tralokinumab for up to 42 months (≤ 1 year in PT and ≤ 2.5 years in the open-label extension ECZTEND), including AEs of special interest (AESI). In ECZTEND, moderate-to-severe AD patients who completed the previous tralokinumab PT received subcutaneous tralokinumab 300 mg every 2 weeks after a 600 mg loading dose; topical corticosteroid use was optional. All AEs were recorded, coded, and classified by severity, causality and outcome. AESIs were predefined in PT based on areas of safety interest for monoclonal antibodies in AD, including eye disorders (e.g. conjunctivitis), skin infections requiring systemic treatment, eczema herpeticum and malignancies diagnosed after dosing. Event rates are presented as the number of events (nE) per 100 patient-years of exposure (PYE). All AEs described were treatment-emergent AEs, defined as AEs reported after the first dosing of the study drug. As of 30 April 2021, the interim safety analysis included 1442 patients from the PT ECZTRA 1, 2, 3, 4, 5 and 7 who had received ≥1 dose of tralokinumab in ECZTEND, with 121.0 weeks mean exposure time on tralokinumab [median 131.5 weeks (IQR 83.4–161.8); min 0.0, max 186.4 weeks]. Total exposure time in ECZTEND was 2446.2 PYE. Overall, 1127 patients experienced an AE (198.7 nE/100 PYE), the majority of which were mild (132.6 nE/100 PYE). The most frequently reported AEs (≥5.0% of patients) were the same as in the PT, including viral upper respiratory tract infection (18.2 nE/100 PYE, mainly reported as the common cold), atopic dermatitis (17.9 nE/100 PYE), upper respiratory tract infection (5.8 nE/100 PYE), headache (4.4 nE/100 PYE) and conjunctivitis (3.8 nE/100 PYE). The rates of AEs were generally lower as compared to short-term rates in the PT. Most of the serious AEs (SAEs; 4.9 nE/100 PYE) were reported as single events without clustering on the type. No events of conjunctivitis AEs were SAEs, and only five patients discontinued due to conjunctivitis AEs. AESI eye disorders, skin infections requiring systemic treatment, eczema herpeticum and malignancies were observed at rates similar to or lower than reported in PT. Consistent safety was demonstrated during up to 42 months of tralokinumab treatment in patients with moderate-to-severe AD. Exposure-adjusted incidence rates of AESIs, including eczema herpeticum and skin infections requiring systemic treatment, were generally lower than rates reported during the short-term, placebo-controlled period up to week 16. Exposure-adjusted incidence rates of conjunctivitis were lower with long-term exposure, and only five patients discontinued due to conjunctivitis. This analysis supports the long-term benefit-risk profile of targeted IL-13 inhibition with tralokinumab for patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

The recent advent of numerous clinical trials for the treatment of moderate-to-severe atopic dermatitis has led to new and emerging therapeutic options for this chronic inflammatory skin disease. With this rapid development has come a lack of consistency in study designs, trial conduct, and statistical analyses. Healthcare providers are challenged to interpret how variations in study parameters may influence clinical trial results. Based on literature review and our experience as clinical trialists, we compiled a list of 22 key study parameters of contemporary clinical trials in moderate-to-severe atopic dermatitis and ranked the top study parameters that may have a significant effect on efficacy results. The top parameters included study comparators, rules for rescue treatment, washout periods for topical and systemic treatments, inclusion criteria such as disease severity by Eczema Area and Severity Index and/or Investigator Global Assessment scores, and the duration of the screening period. We describe considerations for these key parameters, with a focus on between-parameter interactions and effect on efficacy results. This may serve to inform the interpretation of atopic dermatitis clinical trials and raise the profile of the need to harmonize the clinical trial design. Plain Language Summary: Atopic dermatitis (AD) is a skin disease characterized by red, itchy skin that is highly burdensome for patients. Patients with moderate-to-severe disease have large, inflamed skin areas with frequent itching. Recently, the number of clinical trials for drugs that treat moderate-to-severe AD has rapidly increased, with differences in how these trials are designed. There is a need for healthcare providers examining results from different clinical trials to understand how trial design factors might influence study outcomes. In this article, we identify key trial design factors that impact study outcomes, detail how these factors can impact clinical trial results, and explore how these factors interact with one another to affect study outcomes. The five most important design factors, as determined via author surveys, were study comparators (a placebo and/or another drug to which the drug being studied is compared); the rules for the use of rescue treatment (a form of treatment given if an enrolled participant has uncontrolled AD symptoms); washout periods (the time before the trial when previous treatments are stopped to allow them to be cleared from a patient's system); inclusion criteria (that determine which participants are included); and the length of the screening period (the time when patients are assessed to determine if they qualify for participation). By understanding how these key trial design factors impact on study outcomes, healthcare providers may be equipped to better interpret different AD clinical trials. This work also emphasizes the value of harmonizing the AD clinical trial design. [ABSTRACT FROM AUTHOR]

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a realworld setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebocontrolled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Introduction: In phase III trials in adolescents and children with atopic dermatitis (AD), dupilumab significantly decreased global disease severity. However, the effects of dupilumab on the extent and signs of AD across different anatomical regions were not reported. Here we characterize the efficacy of dupilumab in improving the extent and signs of AD across four different anatomical regions in children and adolescents. Methods: A post hoc subset analysis was performed using data from two randomized, double-blind, placebo-controlled, international multicenter, phase III trials of dupilumab therapy in adolescents aged ≥ 12 to < 18 years with moderate-to-severe AD and children aged ≥ 6 to < 12 years with severe AD. Endpoints included mean percentage change in Eczema Area and Severity Index (EASI) signs (erythema, edema/papulation, excoriation, lichenification) and extent of AD (measured by percentage of body surface area [% BSA] involvement) from baseline to week 16 across four anatomical regions (head and neck, trunk, upper extremities, lower extremities). Results: Dupilumab improved both the extent and severity of AD signs across the four anatomical regions. Improvements were shown to be similar across the four anatomical regions for % BSA involvement and for reduction in EASI signs. Improvements in all signs were seen early, within the first 4 weeks of treatment, and were sustained through week 16, across all regions. Conclusions: In pediatric patients 6 years of age and older, treatment with dupilumab resulted in rapid and consistent improvement in the extent and signs of AD across all anatomical regions. ClinicalTrials.gov Identifiers: LIBERTY AD ADOL (NCT03054428) and LIBERTY AD PEDS (NCT03345914). F7z4wqLwbkncM47ga-bUpB Does dupilumab provide improvement in atopic dermatitis across all anatomical regions in children and adolescents? (MP4 48,385 kb) [ABSTRACT FROM AUTHOR]

Background: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy. Objective: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study. Methods: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported. Results: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19. Conclusion: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD. Trial Registries: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822. [ABSTRACT FROM AUTHOR]

Introduction: The Patient-Oriented Eczema Measure (POEM) assesses patient-reported severity of atopic dermatitis (AD) symptoms, whereas the Children's Dermatology Life Quality Index (CDLQI) measures how AD affects health-related quality of life (HRQoL) in children. Although the POEM and CDLQI have established thresholds for clinically meaningful within-patient change in adolescents (aged 12–17 years), there are no defined within-patient responder thresholds for clinically meaningful change in children aged 6–11 years. Methods: Data from the LIBERTY AD PEDS phase 3 randomized, double-blind, placebo-controlled trial of dupilumab in children aged 6–11 years with severe AD were used to define the threshold for within-patient meaningful change in POEM and CDLQI scores. Anchor-based methods were applied to estimate mean change in POEM and CDLQI scores from baseline to week 16, with anchors of a 1-point improvement in the Patient Global Impression of Disease (PGID) scale and an improvement in score of "A little better" on the Patient Global Impression of Change (PGIC) scale. The distribution-based methods, a one-half standard deviation (SD) at baseline and a standard error mean (SEM) were also used. Results: The mean POEM change scores associated with the anchors were a change of − 8.40 with the PGID anchor and − 6.30 with the PGIC anchor. Distribution-based estimates for POEM were one-half SD at baseline of 2.76, with a SEM of 3.32. Mean CDLQI change scores corresponding to the PGID and PGIC anchors were − 7.30 and − 6.80, respectively, while distribution-based estimates for CDLQI were a one-half SD at baseline of 3.69, with a SEM of 3.52. Conclusions: In children with severe AD, an appropriate minimum threshold of clinically meaningful within-patient change was estimated as 6 points for both the POEM and CDLQI scores. Trial registration: ClinicalTrials.gov Identifier: NCT03345914. CU3Ee5FqTp7-UjGF56V1ox What is the clinically meaningful within-person change in Patient-Oriented Eczema Measure and Children's Dermatology Life Quality Index scores in children 6 to 11 years old with severe atopic dermatitis? (MP4 289443 KB) [ABSTRACT FROM AUTHOR]

Studies examining the real-world treatment satisfaction in adults with atopic dermatitis (AD) and the physicians who treat adults with AD are scarce. We sought to characterize treatment satisfaction of adults with AD and physicians’ perceived patient satisfaction with AD treatment. We performed a cross-sectional study of adults > = 18 years of age (modified AD UK Working Party Criteria, age onset < = 18 [N = 767]) with AD and a parallel-physician survey among allergists/immunologists [N = 148], dermatologists [N = 149] and primary care medicine [N = 104]. Logistic regression models were used to examine factors associated with patient treatment satisfaction (PTS) or physician-perceived patient treatment satisfaction (pPTS). Factors associated with increased PTS included female, older age, and receiving a written eczema action plan (EAP). Severe AD, itch, pain, and insomnia, greater impact on partner relationships, feeling not adequately informed about AD causes, and being separated, never married, or living with a partner was associated with less PTS. From the physician’s perspective, mild AD and development of EAP was associated with increase pPTS, whereas being in practice longer was associated with less pPTS. Limitations include the potential for misclassification of AD and the inability to match AD patients to individual physicians. Recognizing which factors are associated with treatment satisfaction can help inform counseling and decision-making strategies, including the use of an eczema action plan, and support patient-physician outcomes alignment. [ABSTRACT FROM AUTHOR]