Upadacitinib Rapidly Improves Patient-Reported Outcomes in Atopic Dermatitis: 16-Week Results from Phase 3 Clinical Trials (Measure Up 1 and 2).

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.

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 1­2 weeks. The extent of the improvements increased through weeks 4­6 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.

Putting the Formulation Back in Foam: Optimizing Seborrheic Dermatitis Treatment Across Diverse Hair Types.

Seborrheic dermatitis (SD) is a chronic inflammatory skin condition that commonly involves the scalp, and thus, affects a diverse demographic with varying hair care needs. Current SD treatments are limited based on optimized formulation, efficacy, adverse events, and lack of placebo-controlled trials. A novel roflumilast foam formulation has emerged as a promising therapeutic option optimally designed for use on the scalp and other hair-bearing areas. We conducted a comprehensive assessment of beauty industry standards, confirming the foam formulation's alignment with industry guidelines and exclusion of potentially harmful ingredients. In addition, consultation with an expert dermatologist panel yielded a strong endorsement, underscoring a high level of confidence in prescribing the foam across diverse hair and skin types.

When Patient Diversity Informs Formulation: Reimagining Treatment for Seborrheic Dermatitis.

Seborrheic dermatitis (SD) impacts a diverse demographic, with treatment effectiveness and suitability varying across hair types and cultural practices. Available shampoo treatments contain surfactants that compromise hair moisture and integrity as well as requiring frequent use, which may not align with the routines of various hair types and cultural hair care practices. Most available topical foams and gels contain high concentrations of drying alcohols that damage hair color and moisture. Newly US Food and Drug Administration (FDA)-approved roflumilast 0.3% foam presents a significant advancement in the treatment of SD owing to its pH-balanced, residue-free formulation that is suited for all hair types, including patients with curly or coiled hair. It presents a culturally inclusive treatment option that offers effective management of SD while maintaining hair health and respecting diverse hair care needs and practices.

More yeast, more problems?: reevaluating the role of Malassezia in seborrheic dermatitis.

Seborrheic dermatitis (SD) is an inflammatory skin disorder and eczema subtype increasingly recognized to be associated with significant physical, psychosocial, and financial burden. The full spectrum of SD, including dandruff localized to the scalp, is estimated to affect half of the world's population. Despite such high prevalence, the exact etiopathogenesis of SD remains unclear. Historically, many researchers have theorized a central, causative role of Malassezia spp. based on prior studies including the proliferation of Malassezia yeast on lesional skin of some SD patients and empiric clinical response to antifungal therapy. However, upon closer examination, many of these findings have not been reproducible nor consistent. Emerging data from novel, targeted anti-inflammatory therapeutics, as well as evidence from genome-wide association studies and murine models, should prompt a reevaluation of the popular yeast-centered hypothesis. Here, through focused review of the literature, including laboratory studies, clinical trials, and expert consensus, we examine and synthesize the data arguing for and against a primary role for Malassezia in SD. We propose an expansion of SD pathogenesis and suggest reframing our view of SD to be based primarily on dysregulation of the host immune system and skin epidermal barrier, like other eczemas.

Taking It Back to Basics: Re-emphasizing the Role of Moisturization in Atopic Dermatitis.

Atopic dermatitis (AD) is a common, burdensome inflammatory skin disease. In recent years, multiple safe and effective monotherapy treatments directly targeting immune dysregulation in AD have been approved and integrated into clinical practice. Although the etiopathogenesis of AD is complex, it is widely recognized that alongside immune dysregulation, skin barrier disruption also plays an essential role in disease pathophysiology. For this reason, regular moisturization has been a foundational mainstay of therapy, consistently recommended by treatment guidelines regardless of disease severity or therapeutic approach. It is vital for healthcare providers to continuously educate patients and caregivers about the importance of optimizing skin barrier function by maintaining proper moisturization as part of their treatment plan and help them make data-driven decisions to navigate the wide array of available products.

The Efficacy and Safety of Bimekizumab for Plaque Psoriasis: An Expert Consensus Panel.

INTRODUCTION: Psoriasis is a chronic inflammatory condition affecting the skin, joints, and several other organ systems with significant disease burden. Bimekizumab is the first monoclonal antibody targeting both interleukin (IL)-17A and interleukin-17F and has demonstrated efficacy for treating moderate to severe psoriasis. Limited guidelines exist for incorporating this drug into clinical practice. The purpose of this study was for a panel of experts in psoriasis management to synthesize current literature and provide consensus statements with guidance on use of bimekizumab. METHODS: A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the use of bimekizumab for moderate to severe psoriasis and psoriatic arthritis. A panel of nine dermatologists with significant expertise in treatment of psoriasis gathered to review the articles and create consensus statements on this new medication. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using Strength of Recommendation Taxonomy criteria. RESULTS: The literature search produced 102 articles that met criteria. A thorough screening of the studies for relevance to the research question resulted in 19 articles. These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 14 consensus statements and recommendations, 12 of which were given a strength of "A", one of which was given a strength of "B", and one of which was given a strength of "C". CONCLUSION: Bimekizumab results in rapid and long-lasting clinical improvement for patients with moderate to severe plaque psoriasis and psoriatic arthritis. It has demonstrated superior efficacy when compared to several other biologics. The safety profile is consistent with other biologics, except for an increased incidence of oropharyngeal candidiasis.

Targeting the Aryl Hydrocarbon Receptor to Address the Challenges of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic relapsing–remitting disease with a multifactorial etiology involving epidermal barrier and immunologic dysfunction. Topical therapies form the mainstay of AD treatment, but options are limited by adverse effects and restrictions on application site, duration, and extent of use. Tapinarof (VTAMA; Dermavant Sciences, Inc.) is a first-in-class, non-steroidal, topical aryl hydrocarbon receptor (AhR) agonist approved for the treatment of plaque psoriasis. AhR is a ligand-dependent transcription factor with wide-ranging roles, including regulation of homeostasis and immune response in skin cells. AhR expression and signaling are altered in many inflammatory skin diseases, and clinical trials with tapinarof have validated AhR as a therapeutic target capable of delivering significant efficacy. Tapinarof cream 1% once daily demonstrated efficacy versus vehicle in adults and adolescents with AD and is being investigated in the ADORING trials for the treatment of AD in adults and children down to 2 years of age. J Drugs Dermatol. 2024;23(2):23-28.  doi:10.36849/JDD.8026.

Dupilumab as Add-on Therapy for Management of Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is characterized by pruritus, urticaria and associated with substantial patient burden. Emerging clinical trial data suggest dupilumab, an anti-IL-4Rα biologic indicated for several Type-2 inflammatory diseases, may have clinical utility for CSU. Here we present real world clinical data evaluating dupilumab as add-on therapy for CSU. We queried our tertiary academic center electronic health record for all patients with an ICD-9/10 code for urticaria with a history of dupilumab use (1/1/2010-6/30/2022). Retrospective chart review was performed to confirm CSU diagnosis, dupilumab use, patient demographics, medical history, treatments, and outcomes. Data were evaluated using summary and descriptive statistics, paired t-test, and Fisher's exact test. A total of 199 patients were identified: 39 had active CSU at time dupilumab initiation; six were excluded due to limited follow up. The most common indication for dupilumab prescription was atopic dermatitis (57.6%), followed by asthma (27.3%). Mean length of dupilumab therapy was 23 months. Following dupilumab, there was a significant reduction in number of patients on daily H1 antagonists (pre: 27 [81.8%]; post: 20 (60.1%); p=0.03), as well as total daily number of antihistamines (pre: 1.95±2.0; post: 0.13±0.2; p=0.01). For patients with moderate/severe vs. mild disease, there was greater improvement in disease control as assessed by physicians global impression of change (77% vs. 30%, p=0.02). In this real-world study, when used as add-on therapy for patients with CSU, dupilumab was associated with improved disease control and decreased H1 blocker use, suggesting a future for dupilumab as an approvedbiologic therapy for the treatment of CSU.

The Clinical Diversity of Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic inflammatory skin condition associated with diverse cutaneous presentations. Differences in clinical phenotypes in skin of color (SOC) patients with AD have been previously noted in race-based analyses. We conducted a narrative review to better characterize the clinical diversity of AD and understand these differences in the context of race, ethnicity, and SOC. Notable racial and ethnic differences in clinical phenotypes have been observed; however, these analyses often are limited by deeper understanding of the true causative factors driving observed differences. Dermatologists should be familiar with the heterogeneity of AD lesional morphology and inflammation severity across all skin types.

Consensus Statements on the Use of Corticosteroid-Containing Topical Medications in Psoriasis.

This article aims to provide consensus statements on the use of corticosteroid-containing topical medications for the management of psoriasis. This Psoriasis Expert Group (PEG) includes dermatologist voting members with expertise in psoriasis who convened and evaluated the use of topical medications and previously published guidelines. A modified Delphi process was conducted to reach consensus results. Two rounds of voting were conducted for each topic and panel consensus was determined.  Nine statements were developed regarding topical medication efficacy, patient quality of life, frequency of application, medication "feel", and safety and tolerability. Dermatologist experts voted on the statements separately. Patients were not polled. All items received agreement: 15 with high consensus and 1 with moderate consensus.  For the treatment of psoriasis, the PEG agreed that patients and physicians prefer topical medications that are effective, provide long-lasting results, have a quick onset of action, and "feel good on the skin" with few adverse effects. The developed consensus statements provide guidance on the topical treatment of psoriasis, including combination therapies, such as a vitamin D and topical corticosteroid analog. These recommendations will be continuously reviewed and updated as more evidence continues to emerge.  April W. Armstrong AW, Reddy R, Khan S, et al. Consensus statements on the use of corticosteroid-containing topical medications in psoriasis. J Drugs Dermatol. 2023;22(8):736-741. doi:10.36849/JDD.7453.

Evaluation of a patient education platform for seborrheic dermatitis.

Seborrheic dermatitis (SD) is a common, burdensome inflammatory skin disorder. Little is known about the identity and quality of videos patients consume on social media to better understand and manage SD. We evaluated three social media platforms-YouTube, TikTok, and Instagram-for content, quality, and popularity. Search terms "seborrheic dermatitis," "dandruff," "cradle cap," and "flaky scalp" identified videos on each platform. The first 50 videos for each keyword were analyzed. After screening, 147 YouTube, 132 Instagram, and 164 TikTok videos were included. Videos were characterized by upload source (healthcare provider/organization [HCP]/non-HCP), quality (accurate/misleading/non-informative), content (educational/personal xperience/entertainment/advertisement), and number of likes/views. Data were analyzed by chi square (categorical) or Kruskal-Wallis (continuous) tests. YouTube contained a higher proportion of videos vs. TikTok and Instagram that were made by HCPs (42.2/19.7/17.7%, respectively) and contained more accurate (52.4/28.0/32.9%), and educational (66.7/38.6/34.4%) content (p < 0.0001 for all). Non-HCPs were responsible for creating the majority of videos across platforms along with most inaccurate/non-informative (65.9/86.8/78.6%) and non-educational (56.5/75.5/71.1%) content (p < 0.0001 for all). Despite lower quality of content and information, TikTok videos had the highest mean views (2,418,872) and likes (184,395) (p < 0.0001 for all). HCP vs. non-HCP-made videos were viewed more frequently only on YouTube. Though views and likes were common for all inaccurate and entertainment/advertisement content, they were most characteristic of TikTok and Instagram (p < 0.0001). These results show a high volume of SD video consumption across all platforms, especially those with lower quality and less informative content, and significant content difference across platforms. Additional studies are needed to better characterize online SD educational content and optimize HCP-led video creation and patient video consumption.

Atopic Dermatitis Across Shades of Skin.

Atopic dermatitis (AD) is a chronic, heterogeneous inflammatory skin disease that is associated with immense patient burden globally. There is increasing appreciation of disparities among patients identified as having skin of color (SOC), which often refers to patients of non-White race or non-European ancestry, but can broadly include individuals from a number of different racial, ethnic, ancestral, and skin pigmentation groups based on definition. In this narrative review, we discuss key terminology as it relates to AD across shades of skin, including modern definitions of 'race', 'ethnicity', and 'SOC'. We then synthesize the current literature describing disparities in AD prevalence, disease recognition, and burden alongside current data regarding genetic and immunologic findings across SOC populations. In the context of these findings, we highlight key concomitant social determinants of health, including environmental factors, socioeconomic status, and access to care, for which race often serves as a proxy for true biological and genetic differences. Finally, we discuss future efforts to shift to a more inclusive understanding of AD to encompass all shades of skin, to ensure equitable representation of diverse populations in high impact research, and intensify efforts to address the critical upstream factors driving observed disparities.

Capturing the Diversity of Dermatology-What's in a Name?

As research related to skin of color (SOC) in dermatology continues to grow, it is increasingly important to precisely define terminology. The terms 'SOC', 'race', and 'ethnicity' are frequently used to analyze differences in dermatologic disease onset, severity, and outcomes. These terms are used interchangeably, are ill-defined across research studies, and frequently conflate biologic and socially constructed categories. SOC has been thought to represent differing degrees of pigment or melanin in the skin, however skin pigment is quite variable among races and ethnicities. Furthermore, certain individuals with less skin pigment may socially consider themselves to be SOC, while the inverse is also true. Fitzpatrick skin phototype classifications in SOC dermatology, while commonly used as an objective measure of diversity, also present with numerous limitations and inaccuracies. We seek to highlight strengths and weaknesses of the current terminology used in SOC dermatology and recommend a more holistic understanding of reported differences, including a framework reflective of upstream socioeconomic, environmental, and historical factors that may be most relevant to reported associations.

Atopic Dermatitis Polypharmacy and Out-Of-Pocket Healthcare Expenses.

BACKGROUND: Atopic dermatitis (AD) out-of-pocket (OOP) expenses are substantial and impact household finances. Prescription polypharmacy and its association with OOP expenses in AD is poorly understood. OBJECTIVE: To characterize prescription polypharmacy and its association with OOP healthcare expenses among individuals with AD. METHODS: An online survey was administered to National Eczema Association members (N=113,502). Inclusion criteria (US resident, age ≥18, self-reported or caregiver of individual with AD) was met by 77.3% (1,118/1,447) of respondents. RESULTS: Polypharmacy (≥5 prescription treatments for AD in the past year) was associated with increased AD severity, poorer control, increased flares, increased healthcare provider visits, and comorbid asthma, allergic rhinitis, food allergy, and skin infections (P≤0.01). Polypharmacy noted with all prescription therapies was most associated with biologic (dupilumab), oral immunosuppressant (azathioprine, cyclosporine, methotrexate, corticosteroids), oral antimicrobial, and topical calcineurin inhibitor (P≤0.0005) use. Respondents with polypharmacy had increased OOP expenditures across numerous categories, including office visit co-pays, prescription medications both covered and not covered by insurance, hospitalization, emergency room visits, mental health services, non-prescription health products such as sleep aids, analgesics, and supplements, and alternative medications (P<0.005). Individuals with polypharmacy had elevated yearly OOP expenses (median [range]: $1200 [$0-$200,000]), higher monthly OOP costs than average, and more harmful household financial impact (P<0.0001 for all). CONCLUSION: Individuals with AD report considerable polypharmacy, which is associated with increased OOP expenses and harmful financial impact. Strategies are needed to reduce polypharmacy, minimize OOP costs, and optimize clinical outcomes. J Drugs Dermatol. 2023;22(2): doi:10.36849/JDD.7038.