Management Of Atopic Dermatitis Research Articles

Dupilumab Safety and Efficacy up to 1 Year in Children Aged 6 Months to 5 Years with Atopic Dermatitis: Results from a Phase 3 Open-Label Extension Study.

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. 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. 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). 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. 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. ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).

The doctors' perception of skin diseases in general practice in Denmark, with emphasis on atopic dermatitis: A descriptive study

AbstractBackgroundSkin symptoms are a common reason for consulting a medical doctor, for example a general practitioner (GP) in countries where GPs function as gatekeepers. Despite this, GPs have very sparse dermatological training in their Residency programme.ObjectivesTo investigate management and challenges of skin diseases, in particular atopic dermatitis (AD), in general practice from the GPs' point of view.MethodsA survey was sent out to all 298 GPs in the North Region of Denmark on 5 April 2022 and data collection continued until 8 June 2022. The survey contained three sections; demographic information about the GP, patients with dermatological problems in general practice, and lastly load, management, and perception of AD in general practice.ResultsA total of 94 GPs (31.5%) responded to the survey. Sixty‐four percent of the GPs reported that 5%–10% of their consultations concerned dermatology, and 25% reported that in more than 10% of their consultations, patients have a secondary skin problem. Top three most frequent skin diagnoses were rated to be seborrhoeic keratoses, children with AD, and acne.ConclusionsConsultations for skin diseases are very common in general practice, and very often, patients bring up their skin issue secondary to another problem. Forty‐three percent of GPs in our study had taken postgraduate training in dermatology, which underlines the need for more dermatological education in the GPs' residency programme. Patients with AD are treated according to guidelines, and GPs find consultations with patients with AD complex. Lastly, there is a high rate of reconsultations for patients with AD.

Oral administration of Lactobacillus delbrueckii subsp. lactis LDL557 attenuates airway inflammation and changes the gut microbiota in a Der p-sensitized mouse model of allergic asthma.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children in developed countries. Although probiotics have shown promise as adjuvant treatments for AD, their mechanisms are not well understood. Building upon our previous studies, we investigated whether Lactobacillus gasseri and its moonlighting glyceraldehyde 3-phosphate dehydrogenase (GAPDH), namely LGp40, could be beneficial in AD management. In AD mouse models (SKH and C57BL/6J mice) with ovalbumin (OVA) and Dermatophagoides pteronyssinus (Der p) allergens, aligning with the "outside-in" and "inside-out" hypotheses, we administered L. gasseri orally and LGp40 intraperitoneally to investigate their protective effects. The evaluation involved measuring physiological, pathological, and immune function parameters. To delve deeper into the detailed mechanism of LGp40 protection in AD, additional assays were conducted using human skin keratinocytes (HaCaT) and monocytes (THP1) cell lines. L. gasseri and LGp40 enhanced skin barrier function and increased skin moisture retention. They also led to reduced infiltration of Langerhans cells in the dermis and mitigated skewed Th2 and Th17 immune responses. Moreover, LGp40 inhibited allergen-induced keratinocyte apoptosis through the blockade of the caspase-3 cascade and reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. These inhibitions were achieved through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. The results of this study provide a novel insight into the mechanism of action of probiotics in the prevention and treatment for allergic disorders through the moonlighting GAPDH protein.

Azulene and Its Derivatives as Potential Compounds in the Therapy of Dermatological and Anticancer Diseases: New Perspectives against the Backdrop of Current Research.

The scientific article focuses on the role of azulene and its derivatives in the therapy of dermatological diseases, presenting the latest laboratory and clinical research as well as prospects for further studies. In a synthetic literature review, various databases such as PubMed, Scopus, Web of Science, and the Database of Polish Scientific Journals were queried to select relevant articles concerning azulene. The conclusions drawn from the thematic analysis of the studies emphasize the multifaceted pharmacological actions of azulene and its derivatives including their anti-inflammatory properties, potential anticancer effects, photoprotective abilities, alleviation of itching, management of atopic dermatitis, and treatment of erectile dysfunction. However, there are certain limitations associated with the application of unmodified azulene on the skin, particularly related to photodecomposition and the generation of reactive oxygen species under UV radiation. These effects, in turn, necessitate further research on the safety of azulene and azulene-derived substances, especially regarding their long-term use and potential application in phototherapy. The authors of this work emphasize the necessity of conducting further preclinical and clinical studies to fully understand the mechanisms of action. Incorporating azulene and its derivatives into the therapy of dermatological disorders may represent an innovative approach, thereby opening new treatment avenues for patients.

MANAGEMENT AND OUTCOME OF ATOPIC DERMATITIS IN PRIMARY HEALTH CARE IN LOW INCOME COUNTRIES : A SYSTEMATIC REVIEW

Background: Atopic dermatitis is a chronic inflammatory skin disorder that is complicated and recurring. It usually first appears in early childhood and might persist throughout maturity. Aims : This systematic review is to review the management and outcome of atopic dermatitis in primary health care in low income countries. Methods: This study demonstrated compliance with all requirements by means of a comparison with the standards established by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020. Thus, the specialists were able to guarantee that the research was as current as feasible. Publications released between 2014 and 2024 were considered for this search strategy. This was accomplished by utilizing a number of distinct online reference sites, including Pubmed, ScienceDirect, and SagePub. It was determined that reviews, previously published works, and partially completed works would not be included. Result: In the PubMed database, the results of our search brought up 539 articles, whereas the results of our search on SCIENCE DIRECT brought up 9.462 articles, our search on SAGEPUB brought up 1.264 articles. The results of the search conducted for the last year of 2014 yielded a total 425 articles for PubMed, 5.474 articles for SCIENCE DIRECT and 613 articles for SAGEPUB. In the end, we compiled a total of 5 papers, 3 of which came from PubMed, 1 of which came from SCIENCE DIRECT and 1 of which came from SAGEPUB. We included five research that met the criteria. Conclusion: In summary, atopic dermatitis is still a major global public health problem, especially for women and young children as well as in high-income nations. It is important to recognize the profound effects on patients, their families, and economies as well as the financial ramifications.

Peripheral ulcerative keratitis associated with tralokinumab therapy: a case report and review of IL-13 inhibitor-associated ocular surface disease

BackgroundDupilumab and tralokinumab are interleukin-binding monoclonal antibodies used to treat systemic atopic disease. Use of these medications in management of atopic dermatitis (AD) is known to cause conjunctivitis. Dupilumab therapy has also been associated with more severe ocular surface disease, which has not previously been described in association with tralokinumab. This report describes a case of tralokinumab-associated conjunctivitis and peripheral ulcerative keratitis and reviews the spectrum and proposed mechanisms of ocular surface disease triggered by these medications.Case presentationA 61-year-old male with no rheumatologic or ocular history presented with bilateral papillary conjunctivitis and right eye peripheral ulcerative keratitis (PUK). PUK was arrested using oral corticosteroids and doxycycline, and long-term control of papillary conjunctivitis was achieved using topical tacrolimus ointment, allowing continuation of effective AD management with tralokinumab.ConclusionThis case report documents ulcerative keratitis occurring in association with tralokinumab therapy for AD, which has previously been described with dupilumab but not tralokinumab. This report demonstrates the need for vigilant ocular surface monitoring for patients on tralokinumab and illustrates successful management and long-term control of adverse ocular events associated with this medication.

The study of chamomile (Matricaria recutita)

In Western culture, chamomile is a well-known plant. Hippocrates, Galen, as well as Asclepius are just a few of the ancient figures who wrote upon their medical use. Paediatricians always want to know if a child's caretaker has used over-the-counter medications or herbal items, and this information should be included in any medication history. Children with GI issues including colic, dyspepsia, and diarrhoea, as well as skin ailments like dermatitis, are frequently treated with chamomile. According to clinical research, chamomile may be beneficial in the management of diarrhoea, colic, and atopic dermatitis. Children don't experience many negative effects. But use chamomile with caution if your child has allergies to ragweed, asters, or chrysanthemums.

Effect of Mixed Probiotics on Ovalbumin-Induced Atopic Dermatitis in Juvenile Mice.

Atopic dermatitis is one of the most common dermatologic problems, especially in children. Given the ability of symbiotic microorganisms in modulating the immune system, probiotics administration has been studied in previous research in the management of atopic dermatitis. However, there are conflicting results between studies. In this study, we aimed to assess the effectiveness of mixed probiotics as a treatment option for atopic dermatitis induced by ovalbumin. BALB/c juvenile mice were classified and divided into the ovalbumin group, mixed probiotic group (ovalbumin + LK), and control group. Except for the control group, all mice were sensitized with ovalbumin to establish a model of atopic dermatitis. The mixed probiotics were given by gavage for 14 days. Mice body weight, skin lesions, skin inflammation, ovalbumin-specific Ig, the number of Treg and CD103+DC, and the expression level of PD-1/PD-L1 were examined. The results showed that mixed probiotics can improve body weight and alleviate skin symptoms. Mixed probiotics reduced serum Th2 inflammatory factors, eosinophils, mast cell degranulation, mast cell count, and the expression of ovalbumin-specific immunoglobulin E/G1 and increased the anti-inflammatory cytokine interleukin-10, Treg cells, CD103+DC cells, and the expression level of PD-1/PD-L1. These findings suggest that mixed probiotics could be a viable treatment option for atopic dermatitis and provide insight into the underlying mechanisms involved.

Photo-responsive polydopamine nanoenzyme microneedles with oxidative stress regulation ability for atopic dermatitis treatment

As a common chronic inflammatory skin disease, atopic dermatitis (AD) troubles many people, while its effective therapy is a challenge. Here, we present novel polydopamine (PDA) nanoenzyme integrated near-infrared ray (NIR)-responsive microneedles (MNs) with antioxidant capacity for AD treatment. Such MNs are composed of a hyaluronic acid (HA) backing layer and hyaluronic acid methacrylate (HAMA) tips that are loaded with PDA nanoenzyme. Owing to the photo-thermal conversion capability of PDA nanoenzyme, the MNs can enhance local microcirculatory blood flow, inhibit bacterial growth, and consequently alleviate inflammation and facilitate lesion repair. Besides, the antioxidant properties of PDA nanoparticles could markedly reduce the ROS production in HaCaT cells under conditions of elevated oxidative stress. Based on these features, we have demonstrated that the MNs could effectively realize remission in AD mouse models. Thus, we believe that the proposed NIR-responsive PDA nanoenzyme MNs could serve as a promising therapeutic approach for the treatment and management of clinic AD.

An OX-Tra'Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis.

The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral role in the pathogenesis of several inflammatory skin conditions, including atopic dermatitis (AD). In particular, T helper 2 (TH2) cells strongly contribute to AD pathogenesis via the production of cytokines associated with type 2 inflammation (e.g., IL-4, IL-5, IL-13, and IL-31) that lead to skin barrier dysfunction and pruritus. The OX40-OX40L interaction also promotes the activation and proliferation of other T helper cell populations (e.g., TH1, TH22, and TH17), and AD patients have demonstrated higher levels of OX40 expression on peripheral blood mononuclear cells than healthy controls. As such, the OX40-OX40L pathway is a potential target for AD treatment. Novel therapies targeting the OX40 pathway are currently in development, several of which have demonstrated promising safety and efficacy results in patients with moderate-to-severe AD. Herein, we review the function of OX40 and the OX40-OX40L signaling pathway, their role in AD pathogenesis, and emerging therapies targeting OX40-OX40L that may offer insights into the future of AD management.

High mobility group box 1 cytokine targeted topical delivery of resveratrol embedded nanoemulgel for the management of atopic dermatitis.

Resveratrol is a polyphenolic compound showing anti-inflammatory activity by inhibition of high mobility group box 1 cytokine responsible for the activation of nuclear factor-κB pathway in atopic dermatitis. To evaluate the efficacy of resveratrol through topical route we have developed resveratrol-loaded nanoemulgel for the effective management of atopic dermatitis in mice model. The resveratrol-loaded nanoemulsion (0.5%, 0.75% and 1% w/w) was optimized by spontaneous nano-emulsification. The optimized resveratrol-loaded nanoemulsions showed average globule size in the 180-230nm range and found to be monodispersed. The resveratrol nanoemulgel was prepared with a SEPINEO™ P 600 gel base and propylene glycol. Ex vivo permeation and retention study resulted in significantly higher skin retention of resveratrol from resveratrol-loaded nanoemulgel than free resveratrol-loaded gel. Preclinical efficacy of resveratrol nanoemulgel displayed promising therapeutic outcomes where, western blotting of skin tissues disclosed a significant reduction in the relative expression of high mobility group box 1, the receptor for advanced glycation end products, toll-like receptor-4 and phosphorylated nuclear factor-κB. Further, real-time polymerase chain reaction also disclosed a significant reduction in pro-inflammatory cytokines such as thymic stromal lymphopoietin, interleukin-4, interleukin-13, interleukin-31, tumor necrosis factor-α and interleukin-6. The histopathological examination of skin sections showed improvement in the skin condition. Collectively, the findings from our study showcased the significant improvement in the atopic dermatitis skin condition in mice model after topical application of resveratrol loaded nanoemulgel.

The Burden of Pediatric Atopic Dermatitis: Quality of Life of Patients and Their Families.

(1) Background: Atopic dermatitis (AD) is one of the most common inflammatory skin conditions, thus having a significant impact on the quality of life (QoL) of patients and their families. We performed a survey to gather more data to help describe the burden of AD in Lithuania and to help expand the treatment plan to this important aspect of the disease. (2) Methods: A cross-sectional study was conducted involving healthy and AD pediatric patients. The assessment instruments used were the Patient-Oriented Eczema Measure (POEM), QoL, and original questionnaires (the original questionnaire was designed by the authors to determine the demographics, medical history, and treatment methods of the respondents). (3) Results: This study included 302 participants in total: 247 AD patients (51% boys) and 55 non-AD patients (51% boys). The mean age for AD patients was 6.8 ± 4.4. years, and this was 10.5 ± 3.1 years for the control patients. A significant difference was found between the QoL questionnaire scores and the Family Dermatology Life Quality Index (FDLQI) score for the atopic dermatitis group (QoL: 6.3 ± 5.6; FDLQI: 7.1 ± 6.9) and controls (QoL 0.5 ± 1.1; FDLQI 2.1 ± 5.9) (p = 0.000). The mean QoL questionnaire score for severe AD was 14.3 ± 6.2 (very large effect), that for moderate AD was 6.9 ± 4.4 (moderate effect), and that for mild AD was 4.4 ± 4.2 (small effect) (p = 0.000). (4) Conclusions: Our study revealed a moderate effect of AD on dermatology-related QoL in patients and their families. It has been shown that increased disease severity was associated with a greater impairment of QoL in both patients and patient's parents. The burden of AD in children and their parents is considerable and should be taken into account in the management of atopic dermatitis.

Physicians’ perspectives and practice in atopic dermatitis management: a cross-sectional online survey in Japan

Data on the problems physicians face when providing care for atopic dermatitis (AD) is limited. To understand the current status of AD management in Japan and identify the difficulties physicians are having and their support requirements, a cross-sectional online survey was conducted using the AD task force of the Japanese Society for Cutaneous Immunology and Allergy. Society members were sent an online questionnaire on demographic information, daily clinical practice, and perceptions of AD management. Using responses to 17 items listed as barriers to the treatment of atopic dermatitis (Question 12) and questions about the treatment difficulty of those items, 284 respondents were divided into three groups using unstratified cluster analysis. These three groups were classified as high-difficulty, medium-difficulty, and low-difficulty groups, and the relationship between physicians’ cognition and daily practice was examined for each group. There were no significant differences in affiliations or specializations among the three clusters. The low-difficulty group had a significantly higher proportion of participants believing that it was possible to achieve long-term remission, satisfaction, and motivation in AD management while carrying out precise assessments of skin lesions as part of their daily practice. Some physicians experience problems in their practice. This results indicate that AD management can be improved if satisfaction and motivation can be increased by providing appropriate support.

Atopic Dermatitis and Abrocitinib: Unraveling the Therapeutic Potential

Abstract: Atopic dermatitis (AD) is a chronic immune-mediated skin condition seriously affecting both children and adults and impacting their quality of life. This complex condition involves genetic predisposition, immune system impairment, and environmental factors. The Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway plays a key role in AD pathogenesis and progression. Abrocitinib presents a hopeful avenue for managing moderate to severe AD, offering significant symptom relief and potential long-term benefits. Its targeted approach to modulating the JAK-STAT pathway holds promise for improved AD management. This comprehensive review explores AD pathogenesis, the chemistry and clinical pharmacology of Abrocitinib, and its safety and efficacy in various trials.

Associations of demographics, aggravating factors, comorbidities, and treatments with atopic dermatitis severity in China: A national cross-sectional study.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder impacting populations worldwide, although its clinical characteristics and patient demographics remain uncharacterized in China. The aim of this study was to investigate the demographics, comorbidities, aggravating factors, and treatments in AD patients across different age groups in China. This cross-sectional study included Chinese AD patients from 205 hospitals spanning 30 provinces. Patients completed dermatologist-led surveys of general medical history, comorbidities, AD-related aggravating factors, and medications. Two-level mixed-ordered logistic regression was used to evaluate aggravating factors. Overall, 16,838 respondents were included in the final analysis (age 30.9±24.1years). The proportion of severe AD was the highest in patients with AD onset at ≥60 years (26.73%). Allergic rhinitis and hypertension were the most common atopic and metabolism-related non-atopic comorbidities, respectively. AD severity was significantly associated with chronic urticaria, food allergies, and diabetes. Aggravating factors including foods, seasonal changes, and psychological factors were also linked to AD severity. The cross-sectional survey implied that severe AD may be related to the undertreatment of effective systemic or topical interventions. To enhance the management of AD, it is crucial to consider both aggravating factors and the increased utilization of systemic immunotherapy. ClinicalTrials.gov Identifier: NCT05316805, CORNERSTONE.

Severe atopic dermatitis in early infancy: characteristics, challenges and new perspectives in clinical practice.

Atopic dermatitis (AD) is the most common skin disease in infants and children with a prevalence of 10% in the first two years of life. In this age group up to 15% are severely affected. "Children are not little adults" - this applies in particular to infants with severe atopic dermatitis. Age-specific clinical aspects (psychosocial, neurocognitive, morphological) of the disease require an adjusted disease management. Considering recent approval of systemic treatment options, early identification of infants and children with severe and early persistent disease is of particular importance also in view of possible prevention of atopic comorbidity. As several inborn errors of immunity (IEI) share features of the atopic phenotype, it is essential for clinicians to distinguish signs of immunodeficiency from severe AD. Here, we describe a practical approach on the basis of clinical history and key dermatological and laboratory findings. Furthermore, this paper is aimed at providing an update on general management of severe AD in early infancy, including recommendations for systemic treatment.

Berdazimer gel for molluscum contagiosum in patients with atopic dermatitis.

Controlling molluscum contagiosum (MC) infections is critical in atopic dermatitis (AD) management. This post hoc analysis assessed the efficacy and safety of berdazimer gel, 10.3% (topical, antiviral, nitric oxide-releasing medication) versus vehicle in MC patients with or without AD. Three Phase 3, multicenter, randomized, double-blind, vehicle-controlled, parallel-group trials (B-SIMPLE[berdazimer sodium in molluscum patients with lesions]1, -2, -4) enrolled patients 6 months and older with 3-70 mollusca. Berdazimer or vehicle was applied once daily to all MC lesions for 12 weeks. Data from three Phase 3 studies were integrated for subgroup efficacy and safety assessments using several weighted meta-analysis approaches. Patients with concurrent AD or a history of AD/eczema were categorized as AD+ subgroup (AD- when absent). Primary efficacy endpoint: complete lesion clearance at Week 12. Safety endpoints included adverse events (AEs) through Week 24 and local skin reactions through Week 12. Of 1598 enrolled patients, 209 (13.1%) were AD+. Baseline mean lesion counts were greater in AD+ (26.4) than AD- (19.3). Complete clearance rates were higher at Week 12 for berdazimer compared with vehicle in AD+ (n = 209; 35.0% vs. 27.4%; odds ratio [OR], 1.3; 95% CI, 0.7-2.5) and AD- (n = 1389; 29.1% vs. 18.9%; OR 1.8; 95% CI 1.4-2.4) subgroups. AEs in AD+ were application-site pain (21.6% with berdazimer vs. 11.9% with vehicle), dermatitis (12.8% vs. 2.4%), and erythema (9.6% vs. 7.1%). Berdazimer gel showed favorable efficacy regardless of AD status. Berdazimer-induced erythema may be indistinguishable from AD symptoms or with inflammatory response upon resolution of molluscum.

Patients’ and caregivers’ perspectives of the atopic dermatitis journey

Background Understanding the patient journey is important to optimize care for patients with atopic dermatitis (AD) and overcome challenges in diagnosis and management. Objective To explore patient and caregiver perspectives regarding their experience with AD. Methods Patients and caregivers of patients with AD completed a pre-meeting survey and were invited to join an advisory board meeting in their country (China, Hong Kong, Ireland, Japan and Lebanon) to discuss the survey results. Data were analyzed descriptively. Results The survey included 31 participants (patients and caregivers) from Hong Kong (n = 7), China (n = 7), Ireland (n = 6), Japan (n = 6) and Lebanon (n = 5). The most challenging factors in the AD journey were management of symptoms before a confirmed diagnosis (68%), sudden recurrence of flares or worsening of symptoms (68%) and lifestyle changes (52%). In terms of overall AD management, 35% of participants indicated that AD was managed well, 23% had a clear treatment plan and 19% were generally satisfied with disease management. A collaborative relationship with healthcare professionals was favored. Conclusion A holistic assessment of AD includes understanding patient and caregiver preferences, needs, experiences and disease perceptions. Addressing the identified gaps may improve the management of AD.

569 - Impact of therapeutic inertia on patient-reported outcomes in moderate-to-severe atopic dermatitis: a 12-month longitudinal study from the TARGET-DERM AD registry

Abstract Background Therapeutic inertia, defined as the delay or reluctance in modifying treatment when goals are unmet, is a significant challenge in managing chronic diseases, including atopic dermatitis (AD). This inertia can lead to suboptimal control of the disease, affecting patient outcomes. Objectives This study aims to evaluate the effect of therapeutic inertia on patient-reported outcomes (PROs) in individuals with moderate-to-severe AD undergoing systemic treatment over 3 to 12 months. Methods We analyzed longitudinal data from the TARGET-DERM AD registry, which includes 3,457 patients with moderate-to-severe AD from 39 centers across the U.S. and Canada. Eligible patients had documented outcomes at the initiation of systemic therapy and at subsequent 3-month intervals up to 12 months of follow-up. We assessed patient-reported outcomes (PROs) to determine the proportion of patients not meeting predefined treatment targets for PROs based on expert consensus. Patients had a validated Investigator Global Assessment (vIGA-AD) score of 3 or more at initiation of either an advanced systemic therapy (AST) such as biologics or JAK inhibitors or a conventional systemic therapy (CST) such as cyclosporine, methotrexate, or prednisone. PROs were evaluated at 3-month intervals up to 12 months, assessing achievement against predefined treatment targets based on expert consensus. PRO measures included Worst-Itch (PROMIS Itch-Severity), POEM, PO-SCORAD, NRS-sleep, and NRS-pain with specific moderate and optimal target levels established for each. Itch-Severity (range: 0–10; moderate target: ≥4-point reduction, optimal target: score ≤1), POEM (range: 0-28; moderate target: ≥4-point reduction, optimal target: score ≤2), PO-SCORAD (range: 0-103; moderate target: score ≤24; optimal target: score ≤10), NRS-sleep and NRS-pain (range: 0-10; moderate target: reduction ≥3-points; optimal target: score ≤1). Results Out of 2107 patients with moderate-to-severe AD, 445 qualifying participants were included (63.8% adult, 62.0% female, 45.4% Non-Hispanic White, mean age of 31 years). Most patients (88.8%) initiated AST, with dupilumab being the most common (86.5%). At 6 months, significant proportions of AST-treated patients failed to reach moderate and optimal targets for itch (67% and 79%, respectively), POEM (46% and 69%), and NRS-sleep (59% and 47%). By 12 months, these figures were similar, with 66% and 88% failing to meet itch targets, 53% and 73% failing to meet POEM targets, and 62% and 45% failing to meet NRS-sleep targets, respectively. A similar pattern was observed for other PROs. CST-treated patients exhibited similar trends. Conclusions The study highlights the profound impact of therapeutic inertia on the quality of life of patients with moderate-to-severe AD. Despite systemic therapy, a considerable proportion failed to meet treatment targets over a 12-month period, underscoring the need for more proactive and responsive treatment strategies in AD management.

529 - Worsening of itch before flaring in patients with moderate-to-severe atopic dermatitis treated with abrocitinib: a post hoc analysis of the phase 3 JADE REGIMEN trial

Abstract Background Patients with atopic dermatitis (AD) often experience a disease course that fluctuates in severity over time, with periods of remission interrupted by flares. Abrocitinib, an oral, once-daily Janus kinase-1 selective inhibitor is approved for the treatment of patients with moderate-to-severe AD. In the phase 3 JADE REGIMEN (NCT03627767) trial, patients achieved an initial response with abrocitinib 200 mg, which was maintained with continued treatment with abrocitinib 200 mg, reduced-dose treatment with abrocitinib 100 mg, or placebo (treatment withdrawal). Following an initial efficacy response, over the 40-week maintenance period some patients across all treatment groups, but predominantly those who switched to placebo, experienced flares, defined as ≥50% loss of Eczema Area and Severity Index response at week 12 and Investigator’s Global Assessment score ≥2, and received rescue therapy. The utility of itch response as a predictor of an upcoming flare in these patients has not yet been determined. Objective To assess itch response before flaring in patients treated with abrocitinib who experienced a flare during the maintenance period of JADE REGIMEN. Methods In JADE REGIMEN, patients aged ≥12 years with moderate-to-severe AD who responded to abrocitinib 200 mg during open-label induction for 12 weeks were randomly assigned 1:1:1 to receive abrocitinib 200 mg, abrocitinib 100 mg, or placebo for up to 40 weeks (maintenance period). Patients who experienced a flare during maintenance received rescue treatment with abrocitinib 200 mg plus topical medicated therapy in an open-label 12-week period. This post hoc analysis evaluated mean itch scores in subsets of patients who did or did not experience flares during the maintenance period. Itch was assessed using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD; © 2016 Pfizer Inc. All rights reserved.) itch numerical rating scale (NRS) item which asked patients, “How itchy was your skin over the past 24 hours?” on a scale from 0 (not itchy) to 10 (extremely itchy). PSAAD scores were collected daily via an e-diary during the screening period and from day 1 through the end of study. Daily itch scores were analyzed at baseline (day of randomization to maintenance treatment groups), from 14 days prior to flaring (from day –14 to day –1), and on the day of flare (day 0) in patients who experienced a flare, and at baseline through 274 days post-randomization in patients who did not experience a flare. Results Of 1233 patients treated with abrocitinib 200 mg in the open-label induction period, 798 (65%) achieved response at week 12 and were randomized to abrocitinib 200 mg (n=266), abrocitinib 100 mg (n=265), or placebo (n=267) in the maintenance period. Across all treatment groups, 442 (55%) patients did not experience a flare and 356 (45%) patients experienced a flare during maintenance. Among patients who did not experience a flare, mean PSAAD itch NRS score remained consistently around 2, with a mean score of 1.5 on day 1 of randomization and 2.1 on day 274 post-randomization. Among patients who experienced a flare, mean PSAAD itch NRS score at baseline was 1.8, which increased to 4.4 on day –14 (14 days before flaring) and continued to increase up to the day of flare (day 0 mean score: 6.4). Conclusions After a successful initial response with abrocitinib, mean itch scores remained stable over time among patients who did not flare. Patients who experienced a flare had worsening of itch from 2 weeks before until the onset of flare. Monitoring of itch may predict onset of flares in patients with moderate-to-severe AD and help inform treatment management or optimization to achieve disease control.