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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]

Abrocitinib, an oral, once-daily, Janus kinase (JAK) 1-selective inhibitor, is approved for the treatment of adults and adolescents with moderate-to-severe atopic dermatitis (AD). Abrocitinib has shown rapid and sustained efficacy in phase 3 trials and a consistent, manageable safety profile in long-term studies. Rapid itch relief and skin clearance are more likely to be achieved with a 200-mg daily dose of abrocitinib than with dupilumab. All oral JAK inhibitors are associated with adverse events of special interest and laboratory changes, and initial risk assessment and follow-up monitoring are important. Appropriate selection of patients and adequate monitoring are key for the safe use of JAK inhibitors. Here, we review the practical use of abrocitinib and discuss characteristics of patients who are candidates for abrocitinib therapy. In general, abrocitinib may be used in all appropriate patients with moderate-to-severe AD in need of systemic therapy, provided there are no contraindications, e.g., in patients with active serious systemic infections and those with severe hepatic impairment, as well as pregnant or breastfeeding women. For patients aged ≥ 65 years, current long-time or past long-time smokers, and those with risk factors for venous thromboembolism, major adverse cardiovascular events, or malignancies, a meticulous benefit–risk assessment is recommended, and it is advised to start with the 100-mg dose, when abrocitinib is the selected treatment option. [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]

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: Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management. Objectives: The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE. Methods: In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg). Results: Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0–5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator's Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores. Conclusions: Consistent with results seen in adults, adolescents, and older children (aged 6–11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population. Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B). Plain Language Summary: Atopic dermatitis (AD) is a chronic inflammatory skin disease that often results in a high disease burden in young children and their families. Patients often need long-term treatment to control their disease symptoms, including itch and rash. Dupilumab treatment for 16 weeks has shown benefits in children aged 6 months to 5 years with moderate-to-severe AD, with an acceptable safety profile. As AD is likely to continue from childhood into adolescence and adulthood, there is a need for data supporting long-term use of dupilumab in young children. In this study, children who completed the 16-week study continued dupilumab treatment for up to 1 year, receiving 200 mg or 300 mg of dupilumab (depending on the child's bodyweight) every 4 weeks. Through the year of treatment, 78.2% of patients reported at least one side effect, most of which were mild or moderate. Only one patient interrupted treatment because of severe skin rash (hives), which was resolved in 1 day. At the end of the year, 36.2% of patients had clear or almost clear skin, and almost all (96.6%) achieved at least 50% improvement in their extent and severity of disease. Additionally, 79.3%, and 58.6% had at least 75% or 90% improvement in their extent and severity of disease. In summary, consistent with results seen in adults, adolescents, and older children, this study showed that 1-year dupilumab treatment provides continued benefits with an acceptable safety profile. These results support long-term continuous use of dupilumab in children aged 6 months to 5 years with moderate-to-severe AD. 5SqqskjZPmoHiNU8WnfbXp What is the long-term safety and efficacy profile in young children with moderate-to-severeatopic dermatitis treated with dupilumab? [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]

This article discusses the utility of the transepidermal water loss (TEWL) to stratum corneum hydration (SCH) ratio in atopic dermatitis (AD). The study compares the performance of the TEWL:SCH ratio to TEWL and SCH alone in differentiating nonlesional skin in AD from healthy controls, differentiating disease severity in nonlesional AD skin, and identifying changes after emollient treatment in nonlesional AD skin. The results show that TEWL alone is the best indicator for distinguishing AD from controls and disease severity, while the TEWL:SCH ratio may be more sensitive to changes after emollient use. The study suggests that the TEWL:SCH ratio could be a useful measure in future dermatology trials. [Extracted from the article]

Background The Harmonising Outcome Measures for Eczema (HOME) initiative has agreed upon the Core Outcome Set (COS) for use in atopic dermatitis (AD) clinical trials, but additional guidance is needed to maximize its uptake. Objectives To provide answers to some of the commonly asked questions about using the HOME COS; to provide data to help with the interpretation of trial results; and to support sample size calculations for future trials. Methods and results We provide practical guidance on the use of the HOME COS for investigators planning clinical trials in patients with AD. It answers some of the common questions about using the HOME COS, how to access the outcome measurement instruments, what training/resources are needed to use them appropriately and clarifies when the COS is applicable. We also provide exemplar data to inform sample size calculations for eczema trials and encourage standardized data collection and reporting of the COS. Conclusions By encouraging adoption of the COS and facilitating consistent reporting of outcome data, it is hoped that the results of eczema trials will be more comprehensive and readily combined in meta-analyses and that patient care will subsequently be improved. [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]

Introduction/Background Clinical trials of up to 52 weeks showed that tralokinumab, a monoclonal antibody that specifically neutralizes interleukin-13, was efficacious and well-tolerated as monotherapy and combination with TCS. Objectives Here, we evaluate the long-term safety of tralokinumab in an integrated analysis of seven phase 3 parent trials (PTs) (NCT03131648, NCT03160885, NCT03363854, NCT03562377, NCT03526861, NCT03761537, NCT04587453), and the ongoing, up to 5-year extension study (ECZTEND; NCT03587805). Methods Two datasets were analyzed: placebo-controlled (initial 16-week period of the PTs), and all-tralokinumab combining PTs with ECZTEND including patients from first dose until end of tralokinumab exposure or data cut-off (April 30th, 2022). In the all-tralokinumab dataset, periods on placebo were disregarded. Treatment-emergent adverse events (AEs) were recorded. AEs of special interest (AESIs) were predefined. Proportions of patients with events and incidence rates (IR) per 100 patient-years of exposure (PYE) were calculated. PYE was defined as time until first event or exposure end, whichever came first, and incidence was defined as first event. Results 2693 patients (≥12 years) received tralokinumab for up to 238.5 weeks (≈4.5 years) with a median exposure time of 76.5 weeks in the all-tralokinumab dataset. Median age at baseline was 33.0 years (min-max; 12-92). 10.4% of patients were 12-17 years. 2307 patients experienced an AE (IR=202.0), most (97.3%) of which were mild-to-moderate. Serious AEs (SAEs) were reported in 226 patients (IR=4.5); SAEs were considered possibly or probably related by the investigator in 50 patients (IR=0.9). No preferred term level SAEs were reported with an IR≥0.1. Discontinuation of treatment due to AEs was low (IR=2.8). AEs leading to drug withdrawal with an IR>0.1 were dermatitis atopic (IR=0.5) and injection site reaction (ISR) (IR=0.2). Frequently reported AEs in the all-tralokinumab dataset were consistent with the placebo-controlled dataset, including nasopharyngitis (IR=18.4), upper respiratory tract infection (IR=6.9), conjunctivitis (IR=5.0), ISR (IR=3.6), conjunctivitis allergic (IR=2.7), and injection site pain (IR=1.5). AESIs, including eye disorders, skin infections requiring systemic treatment, eczema herpeticum, and malignancies, were observed in the all-tralokinumab dataset at rates similar to or lower than the placebo-controlled dataset. Conclusion Long-term use of tralokinumab, for up to 4.5 years, was well-tolerated, and the pattern of AEs was consistent with the initial placebo-controlled treatment period with no new safety signals identified. [ABSTRACT FROM AUTHOR]

Introduction The decision to initiate systemic therapy (ST) in patients with atopic dermatitis (AD) is complex, with no criteria that are globally agreed upon. To aid dermatology providers in this decision-making, the "When to Start Systemic Therapy Checklist" was developed. The checklist comprises three components: (A) clinical severity, (B) subjective burden, and (C) lack of treatment response, each with several criteria. Systemic therapy is indicated when at least one criterion in each component is fulfilled. Objectives To corroborate the validity of this checklist, we evaluated the agreement between the decision to initiate ST using the checklist, against the reference, CorEvitas AD Registry patients prescribed a ST. Methods Adults with moderate-to-severe AD from the prospective, longitudinal CorEvitas AD registry were included in this descriptive analysis (July 2020 – August 2023). Patients were included if they were initiating ST at enrollment (ST group) or not initiating ST at enrollment (non-ST group) but had vIGA-AD® ≥3 and Eczema Area Severity Index ≥12. The checklist criteria were compared against registry outcome measures; when a criterion did not match a measure, either a proxy measure was selected or that part of the questionnaire was excluded. Overall percentage agreement (accord between checklist criteria and ST initiation status [reference standard]) with corresponding 95% confidence intervals (CIs) was calculated. Results In the ST group (n=1488), 97.0% of patients met at least one criterion from section A, 94.1% from section B, and 92.1% for either section A or B. In the non-ST group (n=208), 100% of patients met at least one criterion from section A, 92.3% from section B, and 92.3% from either section A or B. Among patients in the ST group who met at least one criterion each from section A and B, overall percentage agreement was 81.7% (95% CI: 79.8%, 83.5%). Section C, which addresses "lack of treatment response" could not be evaluated due to the absence of relevant data in the registry. Conclusions Nearly all patients initiating ST met at least one criterion from both section A and B of the "When to Start Systemic Therapy Checklist", demonstrating a strong alignment between the checklist sections A and B and disease burden of AD patients in the registry. Subsequent research is needed to assess section C due to registry limitations. Future analyses should examine why some patients with high disease burden and severity remain untreated with systemics. [ABSTRACT FROM AUTHOR]

This is a summary of the original article "An Anti-OX40 Antibody to Treat Moderate-to-Severe Atopic Dermatitis: a Multicentre, Double-blind, Placebo-Controlled Phase 2b Study". Atopic dermatitis (AD) is an inflammatory skin disease caused by a complex interplay of genetic factors, alterations to the skin microenvironment, and immune dysregulation, including T cells that have become uncontrolled. Rocatinlimab is an investigational agent that blocks OX40, a receptor on activated T cells that has an important role in inflammatory conditions such as AD. This summary of research provides an overview of a previously published article on the results of a phase 2b study of patients with moderate-to-severe AD who were treated with different doses of rocatinlimab or placebo and followed for up to 56 weeks. Rocatinlimab significantly improved the symptoms of AD and was well tolerated. The most common adverse events were fever, nasopharyngitis, and chills. This study supports rocatinlimab as a potentially safe and effective treatment for moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Therapeutic options for people with moderate or severe atopic dermatitis refractory to topical therapy have rapidly expanded in recent years. These new targeted immunomodulatory agents—biologics and Janus kinase (JAK) inhibitors—have each demonstrated high levels of efficacy and acceptable safety in mostly placebo-controlled clinical trials for atopic dermatitis, but there is no universally applicable algorithm to help choose between them for a given patient. Hence, patients and physicians should utilize shared decision making, discussing efficacy, safety, mode of delivery, monitoring, costs, speed of onset, and other factors to reach individualized treatment decisions. In this review, we try to aid shared decision making by summarizing the efficacy, safety, and monitoring of biologics and oral JAK inhibitors for adults with atopic dermatitis. Network meta-analyses suggest that higher doses of abrocitinib and upadacitinib are more effective than biologics. They also show that, among biologics, dupilumab is likely more effective than tralokinumab and lebrikizumab. Biologics are generally considered safer than JAK inhibitors, although concerns about JAK inhibitors are mainly extrapolated from older generation JAK inhibitors used in higher-risk populations. We also outline evidence and considerations for choosing and using systemic immunomodulatory treatments for special populations including pregnant individuals, those with human immunodeficiency virus (HIV), hepatitis B and C, end stage kidney disease, and older adults. [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]

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]

Background: Atopic dermatitis is a common chronic, relapsing, and remitting inflammatory skin disorder associated with cutaneous dysbiosis. Current treatment options often fail to adequately control the disease and have unfavorable safety profiles. There is a need for new options that address these treatment shortcomings. Objective: The aim of the study was to evaluate the efficacy, safety, and tolerability of FB-401, a live therapeutic product of 3 strains of Roseomonas mucosa, compared to matching placebo applied topically 3 times per week to participants ages ≥2 years of age with mild-to-moderate atopic dermatitis. Methods: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. The primary outcome was the proportion of participants with 50% improvement in Eczema Area and Severity Index score from baseline at week 16. 154 subjects aged 2 or older with a clinical diagnosis of atopic dermatitis as defined by Hanifin and Rajka criteria with mild or moderate severity were randomized 1:1 via interactive web response system to FB-401 or placebo. Results: The proportion of subjects who achieved the primary outcome was similar between both treatment groups, with no significant treatment group differences observed at any post-baseline visit. The number of treatment-emergent adverse events and the number of subjects with at least one were similar across treatment groups. One serious adverse event not related to treatment was reported. No treatment-emergent adverse events led to treatment discontinuation or study discontinuation. Conclusions: FB-401 showed an acceptable safety profile but failed to prove superior to placebo in treating children and adults with mild-to-moderate atopic dermatitis. [ABSTRACT FROM AUTHOR]

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]

Treat‐to‐target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer‐reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T‐related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician‐ and patient‐reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD. [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]

Ruxolitinib cream is a topical formulation of ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and JAK2. In two phase 3 studies in adults and adolescents (aged ≥12 years) with atopic dermatitis (AD; TRuE‐AD1/TRuE‐AD2), significantly more patients who applied ruxolitinib cream versus vehicle cream achieved Investigator's Global Assessment treatment success (IGA‐TS; IGA score of 0/1 with ≥2‐point improvement from baseline) at week 8 (primary endpoint). This post hoc analysis evaluated the efficacy, safety, and disease control of ruxolitinib cream in patients with AD who did not achieve IGA‐TS at week 8. Patients in TRuE‐AD1/TRuE‐AD2 (N = 1249) were randomized 2:2:1 to apply twice‐daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 weeks followed by a long‐term safety period in which patients applied ruxolitinib cream as needed. In this pooled analysis, clinically meaningful response thresholds included ≥50% improvement in the Eczema Area and Severity Index, ≥2‐point reduction in the Itch Numerical Rating Scale, ≥4‐point improvement in the Dermatology Life Quality Index (DLQI) or ≥6‐point improvement in Children's DLQI, and ≥1‐point reduction in IGA from baseline. Among patients who did not achieve IGA‐TS at week 8 (n = 584), significantly more patients who applied either strength ruxolitinib cream versus vehicle achieved each response threshold at week 8. A response in ≥1 clinically meaningful endpoint was achieved in significantly more patients who applied ruxolitinib cream (93.4%/90.9% for 0.75%/1.5% ruxolitinib cream, respectively) versus vehicle (69.0%, both P < 0.0001). Progressive improvements in disease control were observed, with many patients achieving IGA‐TS by week 52 (55.2%/56.3% for 0.75%/1.5% ruxolitinib cream, respectively). Ruxolitinib cream was well tolerated during the 52‐week study in this patient population. Taken together, these results demonstrate that most patients with AD who did not achieve IGA‐TS at week 8 have clinically meaningful responses to ruxolitinib cream, and continued therapy beyond 8 weeks could result in additional benefit. [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]

Purpose: Environmental factors such as bathing may play a role in atopic dermatitis (AD) development. This analysis utilized data from the Community Assessment of Skin Care, Allergies, and Eczema (CASCADE) Trial (NCT03409367), a randomized controlled trial of emollient therapy for AD prevention in the general population, to estimate bathing frequency and associated factors within the first 9 weeks of life. Methods: Data were collected from 909 parent/newborn dyads recruited from 25 pediatric and family medicine clinics from the Meta‐network Learning and Research Center (Meta‐LARC) practice‐based research network (PBRN) consortium in Oregon, North Carolina, Colorado, and Wisconsin for the CASCADE trial. Ordinal logistic regression was used to conduct a cross‐sectional analysis of the association between bathing frequency (measured in baths per week) and demographic, medical, and lifestyle information about the infant, their family, and their household. Variables were selected using a backwards‐stepwise method and estimates from the reduced model are reported in the text. Results: Moisturizer use (OR = 2.03, 95% CI: 1.54–2.68), Hispanic or Latino ethnicity (OR = 1.97, 95% CI: 1.42–2.72), a parental education level lower than a 4‐year college degree (OR = 2.48, 95% CI: 1.70–3.62), living in North Carolina or Wisconsin (compared to Oregon; OR = 2.12 and 1.47, 95% CI: 1.53–2.93 and 1.04–2.08, respectively), and increasing child age (in days; OR = 1.02, 95% CI: 1.01–1.02) were significantly associated with more frequent bathing, while pet ownership (OR = 0.67, 95% CI: 0.52–0.87) was significantly associated with less frequent bathing. Conclusions: We found significant ethnic, geographic, and socioeconomic variation in bathing frequency before 9 weeks of age that may be of relevance to AD prevention studies. [ABSTRACT FROM AUTHOR]

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]

Background: While the majority of patients with atopic dermatitis (AD) achieve disease control with dupilumab treatment, there is variability in which patients achieve clear disease. The predictors of these responses are currently unclear. Integrated models were developed to evaluate the exposure–response (E-R) relationship of dupilumab in children, adolescents, and adults with AD. Methods: Data from six Phase II and III clinical studies were pooled (2,366 adults [> 18 years], 243 adolescents [≥ 12 to < 18 years] and 359 children [≥ 6 to < 12 years]) for model development. Efficacy was assessed using the Eczema Area and Severity Index (EASI) and Investigator's Global Assessment (IGA). Indirect response models were applied to link measures of efficacy and functional serum dupilumab concentrations. The covariates on individual placebo-corrected response were assessed. Clinical trial scenarios were simulated to compare E-R relationships across age groups. Safety was not explored. Results: After correcting for differences in placebo response and dupilumab exposure: 1) older age, higher body weight, lower baseline thymus and activation-regulated chemokine, and Asian race were associated with slightly lower EASI response, and no clear covariates were identified on IGA response; 2) clinical trial simulations generally showed slightly higher response at a given dupilumab concentration in children compared to adults and adolescents with severe and moderate AD. Conclusions: The collectively tested covariates explain some of the variability in dupilumab response in patients with AD. Patients in all age groups showed adequate response to dupilumab; however, children showed slightly higher drug effects compared to adults and adolescents at equivalent concentrations. [ABSTRACT FROM AUTHOR]

Introduction: Patients with atopic dermatitis (AD) are uniquely susceptible to a number of serious viral skin complications, including eczema herpeticum (EH), caused by herpes simplex virus. This study explored the associations between biomarkers of epithelial barrier dysfunction, type 2 immunity, Staphylococcus aureus infection, and S. aureus-specific immunoglobulin responses in a cohort of AD subjects with and without a history of EH (EH+ and EH−, respectively). Methods: A total of 112 subjects with AD (56 EH+, 56 EH−), matched by age and AD severity, were selected from a registry of over 3000 AD subjects. Logistic regression was used to test the association between history of S. aureus skin infection and history of EH, while controlling for a number of confounders. Results: Compared to those without a history of S. aureus skin infection, subjects with a history of S. aureus skin infection were found to have more than sixfold increased odds of having a history of EH (6.60, 95% confidence interval [CI]: 2.00–21.83), after adjusting for history of other viral skin infections (molluscum contagiosum virus, human papillomavirus), serum total IgE, and IgG against the S. aureus virulence factor SElX. Conclusions: These findings indicate an important relationship between S. aureus skin infections and EH. [ABSTRACT FROM AUTHOR]

Introduction: This real-world, cross-sectional study compared sociodemographic, clinical and treatment characteristics, and patient-reported outcomes (PROs) among racial/ethnic groups in patients with atopic dermatitis (AD) who are candidates for systemic therapy. Methods: This study included adults with dermatologist- or dermatology practitioner-diagnosed AD enrolled in the CorEvitas AD Registry (July 2020–July 2021). All patients initiated systemic therapy within 12 months prior to or at enrollment or had moderate-to-severe AD (vIGA-AD® ≥ 3 and Eczema Area and Severity Index [EASI] ≥ 12) at enrollment. Patients were categorized into five mutually exclusive racial/ethnic groups: non-Hispanic White, Black, Asian, Other/Multiracial, and Hispanic (any race). Patient, clinical, and treatment characteristics were captured at enrollment. Differences in means or proportions of characteristics among racial/ethnic groups were descriptively summarized using effect sizes. Adjusted prevalence ratios and mean differences were estimated (White race/ethnicity group as the reference category) with 95% confidence intervals (CI). Results: Among 1288 patients, 64% (n = 822) were White, 13% (n = 167) Black, 10% (n = 129) Asian, 8% (n = 97) Hispanic, and 6% (n = 73) Other/Multiracial. In adjusted analyses, statistically more severe EASI lichenification was noted among Black compared with White patients at the head and neck (mean difference, 0.21, [95% CI 0.06, 0.36]; p = 0.01), trunk (0.32, [0.17, 0.47]; p < 0.001), upper extremities (0.27, [0.09, 0.44]; p = 0.008), and lower extremities (0.39, [0.21, 0.57]; p < 0.001). Statistically more severe EASI lichenification was observed among Asian vs White patients in certain areas (mean difference, head and neck, 0.22 [0.04, 0.39], p = 0.01; trunk, 0.25 [0.07, 0.43], p < 0.001; lower extremities, 0.22 [0.01, 0.43], p < 0.001) and SCORing for AD lichenification (mean difference: 0.34 [0.15, 0.52]; p < 0.001). Significantly higher mean pruritus over the past 7 days for Black (mean difference: 0.63 [0.01, 1.26] and Hispanic patients (0.60 [0.11, 1.09]; p = 0.03) vs White patients was observed. Among AD clinical features, the prevalence of facial erythema was significantly lower among Black compared with White patients (prevalence ratio = 0.38, [0.22, 0.67]; p = 0.007). Conclusion: Racial/ethnic differences exist in sociodemographic, clinical and treatment characteristics, disease severity, and PROs among real-world AD patients who are candidates for systemic therapy. Recognizing these variations may be of critical importance for dermatologists for the design and delivery of targeted/personalized medicine approaches. [ABSTRACT FROM AUTHOR]

Abrocitinib is a Janus kinase (JAK) 1-selective inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD). Although specific dose recommendations for abrocitinib vary across regional product labels, abrocitinib 100 mg once daily is recommended as a starting and maintenance dose. This review summarizes the efficacy and safety of abrocitinib 100 mg once daily for patients with moderate-to-severe AD based on data from the pivotal phase 3 studies of the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) clinical program, JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE COMPARE (NCT03720470), JADE TEEN (NCT03796676), and JADE REGIMEN (NCT03627767). Preliminary long-term efficacy and safety data are also summarized from the long-term extension study JADE EXTEND (NCT03422822). Expert opinion on use of abrocitinib 100 mg once daily in clinical practice is provided. In addition to efficacy, the decision to use abrocitinib for the treatment of AD should allow for individual patient factors such as age, comorbidities, previous therapy, quality of life, and treatment tolerability, and involve shared decision-making between the patient and clinician. [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: Eczematous dermatitis is a major cause of recalcitrant pruritic eruptions in older adults. Although some medications have been implicated, there are limited data demonstrating the utility of medication changes. Objective: To investigate the utility and possible harms of drug cessation trials (DCTs) in chronic eczematous eruptions in the aging (CEEA). Methods: This is a retrospective cohort study utilizing electronic health records of DCTs in adults older than 65 years with CEEA. Results: We identified 646 patients >65 years with new onset eczematous eruptions, 89 (14%) of whom had no identifiable etiology. In this cohort, 35 patients underwent a total of 40 DCTs. Although there was mention of improvement in 17.5% (7/40), all patients sought tertiary care for their persistent rash. Negative outcomes occurred in 45% (18/40), all of which were due to exacerbation of a comorbidity that the medication was prescribed to treat. Conclusion: Our experience suggests that patients with CEEA undergo DCTs that do not improve their dermatitis and can lead to dangerous worsening of underlying conditions. Further study of the etiology of CEEA is needed. [ABSTRACT FROM AUTHOR]

Background: Tolerability issues including acne, nausea, and headache have been reported with Janus kinase ( JAK) inhibitors for moderate-to-severe atopic dermatitis (AD). Objectives: To report outcomes of tolerability adverse events (AEs) for baricitinib, a JAK1/JAK2 inhibitor, in patients with moderate-to-severe AD. Methods: Acne, headache, and gastrointestinal AEs are reported from placebo-controlled and long-term extensions of pooled data in the baricitinib AD clinical trial program. Proportions of patients with AEs, incidence rates (IRs)/100 patient-years at risk, and median time to onset/duration of AEs were calculated. Results: In 2531 patients treated with baricitinib, most AEs were mild to moderate in severity. Headache was the most common AE of tolerability (median of 14–26 days after first dose of baricitinib, lasting £3 days). IRs of acne were <5 in any group lasting up to a median of 90 days with no severe AEs. Diarrhea was the most common gastrointestinal AE, lasting a median of £7 days. There were few study drug interruptions (n = 6) and permanent discontinuations (n = 5) for tolerability AEs. [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 Tralokinumab is a high-affinity monoclonal antibody that specifically targets IL-13, a driver of inflammation in atopic dermatitis (AD). The ECZTRA 1, 2, 3, and 6 trials demonstrated that tralokinumab is efficacious and safe in adults and adolescents; however, real-world evidence on tralokinumab use is limited. Objectives To assess the change from baseline in clinician-assessed and patient-reported outcomes (PROs) among US adults with AD following 6 months of persistent tralokinumab use after treatment initiation in the CorEvitas AD registry. Methods The CorEvitas AD 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. This analysis includes US patients enrolled in the CorEvitas AD registry who initiated tralokinumab between February 1, 2022 and May 31, 2023, had baseline data, and were persistent on tralokinumab at the 6-month follow-up (defined as a visit occurring 5 to 9 months from tralokinumab initiation). Baseline data were summarized using descriptive statistics and stratified by advanced systemic therapy (AST) experience (defined as any previous history of dupilumab, abrocitinib, or upadacitinib). Outcome measures collected included: validated Investigator's Global Assessment for atopic dermatitis (vIGA-ADTM), ≥50%/≥75% improvement in Eczema Area and Severity Index (EASI) (EASI-50/75), ≥4-point improvement in Dermatology Life Quality Index (DLQI), ≥3-point improvement in mean weekly pruritis numerical rating scale, and mean change in Work Productivity and Activity Impairment (WPAI). Results Among the 60 patients in this analysis, the mean age was 49.1 years and mean AD duration was 15.0 years. The majority of patients were female (34/60, 56.7%), White (51/60, 85.0%), worked full-time (38/60, 63.3%), and AST-naïve (44/60, 73.3%). At baseline, the majority of patients had moderate-to-severe AD based on EASI (EASI≥ 7, 40/60, 67%) and vIGA-ADTM (vIGA-ADTM 3: 50/60, 83.3%; vIGA-ADTM 4: 4/60, 6.7%). Disease severity was lower in AST-experienced patients, all of whom were dupilumab-experienced. A notable proportion of patients experienced improvements in clinician-assessed endpoints and PROs from baseline to 6 months: vIGA-ADTM ≤1 from 6.7% (4/60) to 55.0% (33/60), EASI ≤7 from 33.3% (20/60) to 85.0% (51/60), and DLQI ≤5 from 38.3% (23/60) to 66.7% (40/60). Among patients with EASI ≥7.1 at baseline, 85.0% (34/40) achieved EASI-50 (AST-naïve: 90.9%, 30/33; AST-experienced: 57.1%, 4/7) and 77.5% (31/40) achieved EASI-75 (AST-naïve: 84.8%, 28/33; AST-experienced: 42.9%, 3/7) at the 6-month follow-up. In patients with vIGA-ADTM of 3 or 4 at baseline, 79.6% (43/54) achieved EASI-50 (AST-naïve: 83.3%, 35/42; AST-experienced: 66.7%, 8/12) and 66.7% (36/54) achieved EASI-75 (AST-naïve: 76.2%, 32/42; AST-experienced: 33.3%, 4/12) at follow-up. Among patients with baseline DLQI ≥4, 71.4% (30/42) achieved ≥4-point improvement at follow-up (AST-naïve: 78.1%, 25/32; AST-experienced: 50.0%, 5/10). Of patients with baseline mean weekly pruritus NRS ≥3, 69.8% (37/53) achieved ≥3-point improvement at follow-up (AST-naïve: 70.0%, 28/40; AST-experienced: 69.2%, 9/13). Among the 40 patients employed at both baseline and follow-up visit, improvements were reported in WPAI. Percent impairment at work due to AD decreased by 14.8% (95% CI: -25.6%; -3.9%) and percent overall work impairment due to AD decreased by 15.7% (95% CI: -26.4%; -5.0%). For all 60 patients, non-work activity impairment due to AD decreased by 14.5% (95% CI: -23.9%; -5.1%). Conclusions In this real-world study, patients with AD experienced notable improvements in both clinician-assessed and patient-reported outcomes after 6-months of persistent tralokinumab treatment, regardless of prior AST therapy use. All 16 AST-experienced patients had prior use of dupilumab. These findings support the therapeutic potential of tralokinumab for AD patients, highlighting the need for future studies with longer follow-up period and larger sample size. [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 Atopic dermatitis (AD) is a chronic, inflammatory skin disease with onset usually occurring in childhood. Topical therapy is the mainstay of AD treatment and is typically used prior to systemic therapy in patients with moderate disease. Ruxolitinib (Janus kinase [JAK] 1/JAK2 inhibitor) cream is approved by the US Food and Drug Administration for patients aged ≥12 years with mild to moderate AD, and has demonstrated efficacy and was well tolerated in children (aged 2–11 y) with AD in TRuE-AD3 (NCT04921969), a phase 3, double-blind, randomized, vehicle-controlled study. Objectives Here we investigated the effects of ruxolitinib cream in a subset of patients from TRuE-AD3 with moderate and/or more extensive disease at baseline. Methods TRuE-AD3 included children aged 2–11 years with AD for ≥3 months, an Investigator's Global Assessment (IGA) score of 2 or 3, and an affected body surface area (BSA) of 3%–20%. Patients were randomized 2:2:1 to apply 1.5% ruxolitinib cream, 0.75% ruxolitinib cream, or vehicle cream twice daily for 8 weeks. Rescue treatment was not permitted. Patients from TRuE-AD3 with moderate and/or more extensive disease at baseline (defined as an IGA score of 3, ≥10% affected BSA, or a combined IGA score of 3 and ≥10% BSA) were included in this analysis. Efficacy was assessed as the proportion of patients in each treatment group who achieved IGA treatment success (IGA-TS; a score of 0 or 1 with a ≥2-grade improvement from baseline), ≥75% improvement from baseline in the Eczema Area and Severity Index (EASI-75), and ≥90% improvement from baseline in the Eczema Area and Severity Index (EASI-90) at Weeks 2, 4, and 8. Statistical significance was assessed at Week 8 using exact logistic regression. Patients with missing post-baseline data were imputed as nonresponders. Results Patients in TRuE-AD3 (N=330) had a median (range) age of 6 (2–11) years, 54.2% were girls, and 54.5% were White. The mean (SD) BSA was 10.5% (5.4%), the mean (SD) EASI was 8.6 (5.4), and 252 patients (76.4%) had a baseline IGA of 3. Among patients with an IGA of 3 at baseline, more patients who applied 1.5% ruxolitinib cream or 0.75% ruxolitinib cream versus vehicle achieved IGA-TS (40.0% and 29.1%, respectively, vs 6.1%), EASI-75 (43.0% and 38.8% vs 8.2%), and EASI-90 (17.0% and 21.4% vs 0%) at Week 2. Improvements were also observed at Week 8 (IGA-TS, 59.0% [ P <0.0001] and 37.9% [ P =0.004] vs 14.3%; EASI-75, 64.0% [ P <0.0001] and 48.5% [ P <0.0001] vs 14.3%; EASI-90, 40.0% [ P <0.0001] and 33.0% [ P =0.001] vs 8.2%), with 1.5% ruxolitinib cream consistently resulting in numerically better improvements than 0.75% ruxolitinib cream. Similar improvements were observed with ruxolitinib cream versus vehicle among patients with ≥10% affected BSA at baseline and a combined baseline IGA of 3 and ≥10% BSA. Both strengths of ruxolitinib cream were well tolerated among patients with an IGA of 3 at baseline; no serious treatment-emergent adverse events (TEAEs) were reported. Conclusions Children with moderate and/or more extensive AD in this study had substantially higher rates of clinical responses with ruxolitinib cream monotherapy versus vehicle as early as Week 2 (first assessment), with further improvement throughout the 8-week treatment period. Ruxolitinib cream was well tolerated with no serious TEAEs. [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 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 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 Orismilast is a potent selective phosphodiesterase 4 (PDE4)-B and -D inhibitor, showing significant efficacy in a Phase 2b psoriasis study.1,2 PDE4-B and PDE4-D isoforms are over-expressed in the skin of patients with atopic dermatitis (AD), compared to healthy individuals.3 Enhanced PDE4 activity has also been observed in peripheral blood leukocytes in AD. Orismilast inhibits PDE4-B/D isoforms up to 39 times more potently than apremilast,1 leading to potent suppression of Th1, Th17, and Th2 effector cytokines.1 Objectives To evaluate efficacy and safety of orismilast versus placebo in adults with moderate-to-severe AD. Methods ADESOS is a 16-week, phase 2b, double-blinded, placebo-controlled, dose-finding study assessing efficacy and safety of orismilast in adults with moderate-to-severe AD. Patients were randomized (1:1:1:1) to orismilast 20, 30, 40 mg, or placebo, twice daily. Randomized and dosed patients were included in the Intent-to-Treat Population. Missing data were handled using Multiple Imputation (MI) for the analysis of primary and secondary efficacy endpoints. Results Baseline demographics and disease characteristics were generally balanced across groups for the 233 dosed patients. Significantly more patients achieved IGA0/1 responses at Week 16 in orismilast 20 (n=58), 30 (n=61), and 40 mg (n=59) groups, compared to placebo (n=55) (26.3%, 24.3%, 30.9%, and 9.5%, respectively; all p-values <0.05). All active arms demonstrated a significant ≥4-point reduction in itch NRS at Week 2, compared to placebo (p <0.05). Similarly, Patient Global Impression of Change of "much or very much improved" was significant in active arms compared to placebo at Week 16. Mean percentage changes in EASI at Week 16 were -55.1%, - 52.2%, -61.4%, and -50.4%, in orismilast 20, 30, 40 mg and placebo groups, respectively (p>0,05). Mean EASI at baseline was 23, the least severe reported in Phase 2b/3 studies in moderate-to-severe AD.4 In a subgroup analysis of patients with baseline EASI >21 separation from placebo was increased in the 20 and 40 mg arms, as patients on placebo achieving EASI75 and EASI90 were reduced by 50% and 67%, for the severe population versus the full population. At Week 16, percentages of patients experiencing any Treatment Emergent Adverse Event (TEAE) were orismilast 20 mg, 76%; 30 mg, 79%; 40 mg, 86%; and placebo, 64%. Infection rates were numerically lower in the orismilast groups compared to placebo groups. The most common TEAEs were diarrhea, nausea, and headache, mainly seen within the first month, mostly mild in severity, with few leading to treatment discontinuation. Conclusion Orismilast demonstrated early itch reduction NRS≥4 and statistically significant efficacy versus placebo at Week 16 as measured by IGA0/1. The study was impacted by a high EASI placebo rate; however, in severe patients, the 20 and 40 mg doses separated from placebo for EASI75 and EASI90 measurements, consistent with the overall findings as measured by IGA 0/1, patient-reported efficacy, and objective biomarkers. No new safety signals were identified, and the profile was aligned with the well-established experience from the PDE4 inhibitor class. The most frequent TEAEs were gastrointestinal-related and headache. These data confirm the clinical relevance of high potency PDE4B/D selective inhibition with orismilast, potentially offering a convenient, novel, oral therapy for the treatment of AD and other inflammatory diseases. [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/Background Pruritus is one of the essential features of atopic dermatitis (AD) and is consistently reported by patients as the most burdensome symptom of the disease. Itch not only impacts quality of life but also contributes to furthering AD pathogenesis through the itch-scratch cycle and additional breakdown of the epidermal barrier. A treat-to-target concept established goals to guide treatment with systemic therapies in AD, including those for itch.1-3 Objectives To assess onset and maintenance of optimal itch response according to the treat-to-target concept in adult patients with moderate-to-severe AD treated with dupilumab + concomitant topical corticosteroids (TCS). Methods LIBERTY AD CHRONOS (NCT02260986), a 52-week trial, enrolled patients aged ≥18 years with moderate-to-severe AD. Patients treated with dupilumab every 2 weeks + TCS or placebo + TCS were included in this post hoc analysis. Optimal itch response per the treat-to-target concept was defined as Peak Pruritus Numerical Rating Scale (PP-NRS) score of ≤4, achieved after 6 months of treatment1. We assessed time to optimal itch response, percentage of patients achieving optimal itch response, and maintenance of optimal itch response. For maintenance of optimal itch response, the total number and percentage of weeks with PP-NRS ≤4 were calculated for each patient, and maximum duration was assessed as the longest period of consecutive weeks with PP-NRS ≤4 for each patient. Results Median (interquartile range) PP-NRS score at baseline was 7.7 (6.6–8.5) for patients treated with dupilumab + TCS and 7.6 (6.3–8.6) for patients who received placebo + TCS. Median time (95% CI) to achieve optimal itch response was 29 (22–43) days for patients treated with dupilumab+ TCS and 64 (43–105) days for patients who received placebo + TCS (HR [95% CI] = 1.668 [1.292–2.153]; P < 0.0001). 61.3% of patients treated with dupilumab + TCS achieved optimal itch response at 6 months, compared with 26.7% of those who received placebo + TCS (P < 0.0001). Significantly more patients treated with dupilumab + TCS maintained optimal itch response than patients who received placebo + TCS through 52 weeks. In the dupilumab group, median (Q1–Q3) maintenance of optimal itch response was 40 (11–50) weeks, compared with 3 (0–23) weeks in the placebo group (P < 0.0001), which corresponds to 77.1% of the total study duration (52 weeks) in the dupilumab group, compared with 5.7% in the placebo group. Maximum consecutive duration with optimal itch response was also significantly longer in dupilumab-treated patients than in patients who received placebo (median [Q1–Q3]: 29.2 [4–50] weeks for dupilumab vs 2.0 [0–13] weeks for placebo; P < 0.0001). Conclusions Patients treated with dupilumab + TCS achieved optimal itch response rapidly and significantly faster than patients who received placebo + TCS; 29 days in dupilumab-treated patients compared with 64 days in those who received placebo. Significantly more patients treated with dupilumab + TCS achieved and maintained optimal itch response than patients who received placebo + TCS through 52 weeks. Dupilumab + TCS also led to a significantly longer maintenance of optimal itch response (40 weeks) compared with placebo + TCS (3 weeks). [ABSTRACT FROM AUTHOR]