Real-world clinical, psychosocial and economic burden of atopic dermatitis: Results from a multicountry study.

BACKGROUND: Atopic dermatitis (AD), a relapsing, inflammatory skin disease, is associated with pruritus that can negatively affect patients' quality of life. Understanding the burden of AD is critical for informing and tailoring treatment and disease management to improve patient outcomes. This study characterized global treatment patterns and the clinical, psychosocial and economic burden of moderate-to-severe AD. METHODS: MEASURE-AD was a cross-sectional 28-country study in patients with physician-confirmed moderate-to-severe AD who were either receiving or eligible for systemic therapy for AD. Patients ≥12 years were enrolled between December 2019 and December 2020 while attending routine office or clinic visit. Primary outcomes included Worst Pruritus Numeric Rating Scale (WP-NRS; range: 0-10) and Dermatology Life Quality Index (DLQI; range: 0-30) and Children's DLQI (CDLQI; range: 0-30). Secondary outcomes included physician- and patient-reported clinical, psychosocial and economic burden. RESULTS: Of the 1591 patients enrolled, 1558 (1434 adults and 124 adolescents) fulfilled all patient selection criteria and were included in this analysis. Almost all patients (98.4%) in the total population were using AD medications and more than half (56%) were receiving systemic medication (15% systemic monotherapy). The most used systemic therapies were dupilumab (56.3%), systemic glucocorticoids (18.1%) and methotrexate (16.2%). Mean WP-NRS was 5.3 in the total population, and most patients (≥55%) reported moderate-to-severe pruritus (WP-NRS ≥4). Mean DLQI was 10.8 and mean CDLQI was 9.6. Secondary endpoints demonstrated substantial clinical, psychosocial, and economic burden of disease. Subgroup analysis demonstrated that patients receiving systemic therapy had lower disease burden than those not taking systemic medications. CONCLUSIONS: While systemic therapy lowers overall disease burden, patients with moderate-to-severe AD continue to have substantial multidimensional disease burden and uncontrolled disease. Overall, there is a need for effective disease management, including effective treatments that improve patients' psychosocial outcomes and reduce the economic burden of AD.

The role of micrometastasis in high-risk skin cancers.

The propensity to metastasize is the most important prognostic indicator for solid cancers. New insights into the mechanisms of early carcinogenesis have revealed micrometastases are generated far earlier than previously thought. Evidence supports a synergistic relationship between vascular and lymphatic seeding which can occur before there is clinical evidence of a primary tumour. Early vascular seeding prepares distal sites for colonisation while regional lymphatics are co-opted to promote facilitative cancer cell mutations. In response, the host mounts a global inflammatory and immunomodulatory response towards these cells supporting the concept that cancer is a systemic disease. Cancer staging systems should be refined to better reflect cancer cell loads in various tissue compartments while clinical perspectives should be broadened to encompass this view when approaching high-risk cancers. Measured adjunctive therapies implemented earlier for low-volume, in-transit cancer offers the prospect of preventing advanced disease and the need for heroic therapeutic interventions. This review seeks to re-appraise how we view the metastatic process for solid cancers. It will explore in-transit metastasis in the context of high-risk skin cancer and how it dictates disease progression. It will also discuss how these implications will influence our current staging systems and its consequences on management.

Cross-sectional burden-of-illness study in atopic dermatitis (MEASURE-AD) in Australia and New Zealand reveals impacts on well-being.

OBJECTIVES: To describe disease burden in individuals with moderate-to-severe atopic dermatitis (AD) in Australia and New Zealand (ANZ) and compare it with other geographic regions. METHODS: This multicentre, cross-sectional, observational study (MEASURE-AD) recruited consecutive adolescent and adult patients attending dermatology clinics in 28 countries. Data collected included scores of pruritus, disease severity, sleep, pain, disease control, work and quality of life. RESULTS: This study included 112 ANZ participants (Australia n = 72; New Zealand n = 40) from December 2019 to December 2020. Treatments included topicals (85.7% of patients), non-biologic systemic therapy (28.6%), phototherapy (9.8%) and dupilumab (4.5%). Mean Eczema Area and Severity Index (EASI) score was 22.3 (95% CI 19.6-25.0) and Patient-Oriented Eczema Measurement (POEM) score was 18.4 (95% CI 16.8-20.0). Pruritus Numerical Rating Scale (NRS) was 6.0 (95% CI 5.5-6.6) (50% had severe pruritus) and Dermatology Life Quality Index (DLQI) 14.3 (95% CI 12.8-15.8). ADerm-Impact sleep domain score was 15.1 (95% CI 13.2-16.9). ADerm-Symptom Scale worst skin pain domain score was 5.0 (95% CI 4.3-5.6). Work Productivity and Activity Impairment (WPAI) percentages indicated work and productivity impairment. Inadequately controlled AD was self-reported by 41%, with 9.7 flares in the past 6 months. Scores of pruritus, disease severity, sleep, pain, disease control and quality of life in ANZ were often the highest of all the geographic regions studied. CONCLUSION: ANZ patients with AD have a high disease burden, which extends across multiple facets of daily life. Many are inadequately controlled with existing therapies.

Minimum labelling requirements for dermatology artificial intelligence-based Software as Medical Device (SaMD): A consensus statement.

BACKGROUND/OBJECTIVES: Artificial intelligence (AI) holds remarkable potential to improve care delivery in dermatology. End users (health professionals and general public) of AI-based Software as Medical Devices (SaMD) require relevant labelling information to ensure that these devices can be used appropriately. Currently, there are no clear minimum labelling requirements for dermatology AI-based SaMDs. METHODS: Common labelling recommendations for AI-based SaMD identified in a recent literature review were evaluated by an Australian expert panel in digital health and dermatology via a modified Delphi consensus process. A nine-point Likert scale was used to indicate importance of 10 items, and voting was conducted to determine the specific characteristics to include for some items. Consensus was achieved when more than 75% of the experts agreed that inclusion of information was necessary. RESULTS: There was robust consensus supporting inclusion of all proposed items as minimum labelling requirements; indication for use, intended user, training and test data sets, algorithm design, image processing techniques, clinical validation, performance metrics, limitations, updates and adverse events. Nearly all suggested characteristics of the labelling items received endorsement, except for some characteristics related to performance metrics. Moreover, there was consensus that uniform labelling criteria should apply across all AI categories and risk classes set out by the Therapeutic Goods Administration. CONCLUSIONS: This study provides critical evidence for setting labelling standards by the Therapeutic Goods Administration to safeguard patients, health professionals, consumers, industry, and regulatory bodies from AI-based dermatology SaMDs that do not currently provide adequate information about how they were developed and tested.

The Treat-to-Target Project in Atopic Dermatitis: One Year On.

Atopic dermatitis is a chronic skin condition for which a range of systemic treatments have recently been approved. A treat-to-target strategy has been developed previously alongside an algorithm to guide the management of patients with atopic dermatitis. Here, we review the strategy and algorithm in the context of the evolving therapeutic landscape, and identify areas for further refinement and development.

Australian consensus: Treatment goals for moderate to severe psoriasis in the era of targeted therapies - Adult patients.

BACKGROUND: Over the last decade, the treatment landscape for moderate-severe psoriasis has rapidly evolved. The Australasian College of Dermatologists sought to review and update previously published treatment goals for moderate-severe psoriasis. METHODS: A modified Delphi approach was used. Comprehensive literature review and guideline evaluation resulted in the development of statements and other questions to establish current clinical practices. Two rounds of anonymous voting were undertaken, with a collaborative meeting held in between to discuss areas of discordance. Overall, consensus was defined as achievement of ≥75% agreement in the range 7-9 on a 9-point scale (1 strongly disagree; 9 strongly agree). RESULTS: Consensus was achieved on 26/29 statements in round 1 and a further 20 statements in round 2. There was strong agreement to expanding the classification/definition of psoriasis severity by including a choice of metrics, incorporating quality of life measures, and widening the scope of high-impact sites. Consensus was also reached on revised treatment response criteria, which were then incorporated into a new treatment algorithm. There was discordance with the current requirement to undertake a trial with established systemic agents before accessing targeted therapy. CONCLUSION: The ability of new targeted treatment options to change the narrative in psoriasis patient care can only be properly realised if challenges to timely and equitable access are addressed. The proposed framework for the assessment, classification and management of moderate-severe psoriasis aligns with international recommendations. Its adoption into Australian clinical practice is hoped to improve treatment outcomes and patients' satisfaction with their care.

Informing a position statement on the use of artificial intelligence in dermatology in Australia.

Artificial Intelligence (AI) is the ability for computers to simulate human intelligence. In dermatology, there is substantial interest in using AI to identify skin lesions from images. Due to increasing research and interest in the use of AI, the Australasian College of Dermatologists has developed a position statement to inform its members of appropriate use of AI. This article presents the ACD Position Statement on the use of AI in dermatology, and provides explanatory information that was used to inform the development of this statement.

Phase 3 efficacy and safety of abrocitinib in adults with moderate-to-severe atopic dermatitis after switching from dupilumab (JADE EXTEND).

BACKGROUND: Abrocitinib efficacy by prior dupilumab response status in patients with moderate-to-severe atopic dermatitis has not previously been assessed in phase 3 studies. OBJECTIVE: Examine efficacy and safety of abrocitinib among patients who received prior dupilumab. METHODS: Patients with moderate-to-severe atopic dermatitis received abrocitinib 200 mg or 100 mg once daily in JADE EXTEND (phase 3 extension) after dupilumab in double-blind, placebo-controlled phase 3 JADE COMPARE. RESULTS: Among prior dupilumab responders, ≥75% improvement in Eczema Area and Severity Index was achieved in 93.5% and 90.2% of patients who received 12 weeks of abrocitinib 200 mg and 100 mg, respectively; ≥4-point improvement in Peak Pruritus Numerical Rating Scale was achieved in 89.7% and 81.6%, respectively. Among prior dupilumab nonresponders, ≥75% improvement in Eczema Area and Severity Index was achieved with abrocitinib 200 mg and 100 mg in 80.0% and 67.7% and ≥4-point improvement in Peak Pruritus Numerical Rating Scale in 77.3% and 37.8%, respectively. Most common adverse events among abrocitinib-treated patients were nasopharyngitis, nausea, acne, and headache. Conjunctivitis occurred less frequently with abrocitinib in comparison to prior dupilumab. LIMITATIONS: Short-term, 12-week analysis; no placebo arm. CONCLUSION: Efficacy and safety profile of abrocitinib in JADE EXTEND supports the role of abrocitinib as a treatment for patients with moderate-to-severe atopic dermatitis, regardless of prior dupilumab response status.

Method of Assessing Skin Cancerization and KeratosesTM (MASCK™): development and photographic validation in multiple anatomical sites of a novel assessment tool intended for clinical evaluation of patients with extensive skin field cancerization.

BACKGROUND: A range of 'field-directed' treatments is available for the management of extensive skin field cancerization (ESFC), but to date, the only validated objective quantitative tools are limited to assessment of actinic keratoses (AKs) affecting the head. AIMS: To develop a versatile quantitative instrument for objective clinical assessment of ESFC and perform initial internal validation across multiple anatomical zones. METHODS: The study comprised instrument development, pilot testing and instrument refinement and two rounds of reliability and inter-rater validation testing. The study was noninterventional and used a convenience sample of de-identified patient photographs selected based on preset criteria. An expert panel developed the instrument and scoring system via a modified Delphi voting process. A sample of 16 healthcare professionals from multiple specialties undertook the pilot testing, and a panel of seven dermatologists were involved in validation testing. Validation was determined by assessment of overall inter-rater agreement using Gwet chance-corrected agreement coefficients (ACs). RESULTS: The instrument produced, called the Method for Assessing Skin Cancer and Keratoses™ (MASCK™), comprises the Skin Field Cancerization Index (SFCIndex), derived from area of skin involvement and AKs (number and thickness), a global assessment score and a cancer-in-zone score, and uses Likert scales for quantitative scoring. The SFCIndex is a composite score comprising the number and thickness of AKs multiplied by area of skin involvement. ACs for the SFCIndex components, the overall SFCIndex score and the global assessment score were > 0.80 (rated 'almost perfect') while the AC for the cancer-in-zone metric was lower (0.33, rated 'fair'). Internal consistency was demonstrated via positive correlation between the overall SFCIndex score and the global assessment score. CONCLUSIONS: Our study found near-perfect agreement in inter-rater reliability when using MASCK to assess the severity of ESFC in multiple anatomical sites. Further validation of this novel instrument is planned to specifically assess its reliability, utility and feasibility in clinical practice.

Dupilumab-associated ocular surface disease: An interdisciplinary decision framework for prescribers in the Australian setting.

BACKGROUND/OBJECTIVES: Dupilumab-associated ocular surface disease (DAOSD) is of particular relevance in patients with atopic dermatitis (AD). Guidance on DAOSD assessment and management in the Australian setting is needed to reduce its impact and minimise disruption to treatment. METHODS: A systematic review of the literature was undertaken to identify data pertaining to the incidence, pathophysiology, risk factors and management of DAOSD. A critical review of this literature was used to inform a decision framework for dupilumab-prescribers and develop a graded severity scoring tool to guide appropriate management options. RESULTS: DAOSD typically emerges within 4 months of commencing dupilumab and the occurrence of new events diminishes over time. The reported incidence varies widely depending on the nature and source of the data: 8.6-22.1% (clinical trials programme), 0.5-70% (real-world data; differences in study size, duration of follow-up, ophthalmologist intervention, use of prophylaxis). Occurrence increases with AD severity and in patients with prior history of ocular disease; pathophysiology is still to be fully characterised. Management options have evolved over time and include lubricants/artificial tears, corticosteroids, calcineurin inhibitors, antihistamines, anti-inflammatory agents and antimicrobial agents. Current therapies aim to resolve symptoms or reduce severity to levels sufficiently tolerable to enable continuation of dupilumab therapy. CONCLUSIONS: Recommendations for DAOSD assessment and management include identification of high-risk patients, vigilance for red flags (keratoconus, herpetic and bacterial keratitis), regular assessment of symptom severity (before and during dupilumab therapy), conservative management of mild DAOSD by the prescribing physician and ophthalmologist referral for collaborative care of moderate-severe DAOSD and high-risk patients.

Development of melanoma clinical quality indicators for the Australian melanoma clinical outcomes registry (MelCOR): A modified Delphi study.

BACKGROUND: Clinical quality registries aim to identify significant variations in care and provide anonymised feedback to institutions to improve patient outcomes. Thirty-six Australian organisations with an interest in melanoma, raised funds through three consecutive Melanoma Marches, organised by Melanoma Institute Australia, to create a national Melanoma Clinical Outcomes Registry (MelCOR). This study aimed to formally develop valid clinical quality indicators for the diagnosis and early management of cutaneous melanoma as an important step in creating the registry. METHODS: Potential clinical quality indicators were identified by examining the literature, including Australian and international melanoma guidelines, and by consulting with key melanoma and registry opinion leaders. A modified two-round Delphi survey method was used, with participants invited from relevant health professions routinely managing melanoma as well as relevant consumer organisations. RESULTS: Nineteen participants completed at least one round of the Delphi process. 12 of 13 proposed clinical quality indictors met the validity criteria. The clinical quality indicators included acceptable biopsy method, appropriate excision margins, standardised pathology reporting, indications for sentinel lymph node biopsy, and involvement of multidisciplinary care and referrals. CONCLUSION: This study provides a multi-stakeholder consensus for important clinical quality indicators that define optimal practice that will now be used in the Australian Melanoma Clinical Outcomes Registry (MelCOR).

A daily regimen of a ceramide-dominant moisturizing cream and cleanser restores the skin permeability barrier in adults with moderate eczema: A randomized trial.

The dysfunctional skin barrier in eczema patients may be attributed to decreased levels of ceramides in the stratum corneum. The aim of this study was to determine whether a two-part system consisting of a ceramide-dominant physiological lipid-based moisturizing cream and cleanser could ameliorate the signs and symptoms of moderate eczema in adults over 28 days compared to placebo. Assessments were conducted at baseline and every 7 days thereafter. Eczema area severity index score decreased significantly across all time points in both groups compared to baseline (P < .0001), however, this decrease was not significant between groups at day 28 (P = .7804). In contrast, transepidermal water loss and skin hydration significantly improved over time in the active group, while it either stayed the same or worsened in the placebo group (P = .0342 and P < .0001, respectively). There was no difference in the use of mometasone furoate as rescue medication over time between groups (P = .1579). Dermatology life quality index scores improved significantly in both groups (P < .0001), with no difference between groups (P = .5256). However, patient satisfaction was greater in the active compared to the placebo group for several parameters including relief of itch, dry skin, skin softness and smoothness (all P < .05). No patients withdrew from the study due to adverse events (AEs) and there were no serious AEs. The ceramide-dominant moisturizing cream and cleanser safely restores skin permeability and improves the signs and symptoms of eczema in adults.

Treat-to-Target in Atopic Dermatitis: An International Consensus on a Set of Core Decision Points for Systemic Therapies.

Currently no treat-to-target framework to guide systemic treatment in adults with moderate-to-severe atopic dermatitis exists. We sought to reach international consensus through an eDelphi process on a core set of recommendations for such an approach. Recommendations were developed by an international Steering Committee, spanning 3 areas (Guiding Principles, Decision Making, and Outcome Thresholds) and 2 specific time-points; an initial acceptable target at 3 months and an optimal target at 6 months, each based on improvements in patient global assessment plus at least one specific outcome domain. These treat-to-target- orientated recommendations were evaluated by an extended international panel of physicians, nurses and patients. Proposed recommendations were rated using a 9-point Likert scale; for each recommendation, consensus agreement was reached if ≥ 75% of all respondents rated agreement as ≥ 7. Consensus on 16 core recommendations was reached over 2 eDelphi rounds. These provide a framework for shared decision-making on systemic treatment continuation, modification, or discontinuation.

Recruitment of adults with moderate eczema for a randomised trial: Comparison of traditional versus modern methods.

BACKGROUND: Clinical trial recruitment is challenging for investigators who often overestimate the pool of qualified, willing subjects. Moreover, there is a paucity of literature, particularly in dermatology, regarding recruitment and the comparative success of advertising strategies. METHODS: Both 'traditional' (physician referral, newspaper and radio advertisements, letterbox drops, posters/flyers, word-of-mouth) and 'modern' (patient recruitment services, social media, Google advertisements, websites, email) recruitment methods were used to enrol 100 patients (>18 years) diagnosed with moderate eczema for a randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of a topical eczema treatment over 4 weeks. The relationships between recruitment method and patient age, sex, race, study completion and costs were analysed. RESULTS: The majority of patients recruited were young, with millennials and Gen Z comprising 77% of the study population. Both traditional and modern recruitment methods were equally successful in recruiting younger patients, with older patients predominately recruited by traditional methods. Eighty per cent more men were recruited by traditional compared to modern methods, whilst 67% more women than men were recruited by modern methods. Recruitment method neither appeared to be influenced by race, nor did it effect whether patients completed the study. Costs per enrolment were similar for both methods. CONCLUSIONS: This study shows that despite the high proportion of young patients and the rising popularity of social media and increased internet use, a combination of both traditional and modern recruitment methods was required to successfully meet the trial enrolment target of 100 adult patients with moderate eczema.

The effectiveness of Janus kinase inhibitors in treating atopic dermatitis: A systematic review and meta-analysis.

Primary studies have presented conflicting results on the efficacy of Janus kinase (JAK) inhibitors in treating atopic dermatitis. Hence, it is important to determine the summary effect of JAK inhibitors in order to guide the clinical application of this potentially beneficial drug. To determine the efficacy of JAK inhibitors in treating atopic dermatitis in all age groups. A systematic review with meta-analyses of randomized controlled trials (RCTs) reporting on the effect of JAK inhibitors on the signs and symptoms of atopic dermatitis were conducted. Six electronic databases, registries, and search engines (PubMed, Cochrane Central Register of Controlled Trials [CENTRAL], Google Scholar, ScienceDirect, Clinical.gov, and WHO ICTRP) were searched from inception to September, 2019. The search terms include "atopic dermatitis," "eczema," and "Janus kinase inhibitor." The search was restricted to humans. A total of 413 studies were identified through the database search and hand-searching. After the selection process, five RCTs were included in this systematic review. A meta-analysis of three studies showed that JAK inhibitors were effective in reducing Eczema Area and Severity Index (P = .0001) and pruritus scores (P = .0001). JAK inhibitors appear to be effective in treating atopic dermatitis. Future studies should aim to evaluate its cost-effectiveness and availability to patients especially in developing countries.

The efficacy and safety of tacrolimus as mono- and adjunctive therapy for vitiligo: A systematic review of randomised clinical trials.

There is currently no definitive treatment for vitiligo; various modalities include immune modulators phototherapy and skin camouflage. We investigated the efficacy and safety of topical tacrolimus either as monotherapy or combined therapy in the treatment of vitiligo. Electronic systematic search of the literature was carried out using four major databases. Randomised clinical trials (RCTs) that reported the use of topical tacrolimus in the treatment of human vitiligo have been included in a systematic review and meta-analysis. Meta-analysis was conducted via RevMan, and risk of bias was assessed through the Cochrane quality assessment tool. The protocol was published through PROSPERO (CRD42018112430). A total of 19 studies including 814 patients were included in our systematic review. The random-effects-model meta-analysis of two studies revealed that the tacrolimus and narrowband ultraviolet B (NB-UVB) combination therapy rates is better than NB-UVB alone in inducing >75% repigmentation [RR 1.34 (95% CI: 01.05-1.71), P = 0.02]. Tacrolimus and steroids had similar potency in acheiving >75% repigmentation [RR 1.02 (95% CI: 0.19-5.51), P = 0.98]. Meta-analysis of two studies revealed that the fractional laser and tacrolimus combination therapy is no better than tacrolimus alone in causing >75% repigmentation [RR 2.11 (95% CI: 0.87-5.09), P = 0.10]. Further investigating tacrolimus as mono- or adjuvant therapy for vitiligo is highly recommended. Combining tacrolimus to other treatment options such as steroids, phototherapy and laser may be superior to using tacrolimus alone.

Practice guidelines for teledermatology in Australia.

Despite the potential of teledermatology to increase access to dermatology services and improve patient care, it is not widely practised in Australia. In an effort to increase uptake of teledermatology by Australian dermatologists and support best practice, guidelines for teledermatology for the Australian context have been developed by The University of Queensland's Centre for Online Health in collaboration with The Australasian College of Dermatologists' E-Health Committee. The guidelines are presented in two sections: 1. Guidelines and 2. Notes to support their application in practice, when feasible and appropriate. Content was last updated March 2020 and includes modalities of teledermatology; patient selection and consent; imaging; quality and safety; privacy and security; communication; and documentation and retention of clinical images. The guidelines educate dermatologists about the benefits and limitations of telehealth while articulating how to enhance patient care and reduce risk when practicing teledermatology.

A review of literature supporting the development of practice guidelines for teledermatology in Australia.

Despite the potential of teledermatology to increase access to dermatology services and improve patient care, it is not widely practised in Australia. In an effort to increase uptake of teledermatology, Australian-specific practice guidelines for teledermatology are being developed by the Australasian College of Dermatologist. This paper reports finding from literature reviews that were undertaken to inform the development of these guidelines. Results cover the following sections: Modalities of teledermatology; Patient selection and consent; Imaging; Quality and safety; Privacy and security; Communication; and Documentation and retention. The document educates providers about the benefits and limitations of telehealth while articulating how to enhance patient care and reduce risk when practicing teledermatology.

Chemical peels: A review of current practice.

Chemical peels belong to a group of cutaneous resurfacing procedures that are used in the treatment of photoageing, inflammatory dermatoses, epidermal proliferations, pigmentary disorders and scarring. This review describes best current practice, highlights recent advances in chemical peel technology and discusses the recommended uses for different peel types. It also presents the results of a survey of the chemical peeling practices of 30 Australian dermatologists.