Patient-reported burden in adults with atopic dermatitis: an international qualitative study.

The objective was to study a large, international, ethnically diverse population of patients with atopic dermatitis (AD) to support the creation of patient-centric recommendations for AD management. Qualitative data were generated from 45-min, 1:1 telephone interviews conducted across 15 countries in each patient's native language. Interviews explored the impact of AD on patients' lives, patients' most important symptoms, treatment expectations, and treatment decision-making. Participants were also questioned on their current knowledge of AD scoring systems and what was most important to include in these tools. In total, 88 adult patients (≥ 18 years old) receiving treatment for AD were recruited through a market research database, clinician referrals, and local advertising. All patients were screened to ensure a balanced and diverse sample in terms of age, gender, educational level, employment status, geographic location, and AD severity. Patients involved in market research or activities supporting advocacy groups within the previous 6 months or affiliated with or employed by pharmaceutical companies were excluded. AD had a substantial impact on patients' lives. Itch, skin redness, and dry/flaky skin were the most frequently reported symptoms, with > 75% of patients experiencing these symptoms every 1-3 days. Mental health issues were common and resulted in the greatest negative impact on patients' daily lives. Patients perceived clinicians to underestimate the burden of their AD. Patients had little awareness of AD scoring systems and indicated a preference for these to be more clearly incorporated in clinical practice. For an ideal scoring system, patients favored using a combination of patient-reported and clinician-reported outcomes to reflect disease burden and ensure consistency across all settings. This global study generated diverse patient perspectives on the disease burden of AD, their expectations of treatment, and their views on AD scoring methods. These data provide evidence to support the development of patient-centric recommendations for AD management.

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.

Baseline Characteristics of Canadian Patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: The Psoriasis Longitudinal Assessment and Registry (PSOLAR) is a global, prospective, longitudinal, disease-based registry. It serves as a post-marketing safety commitment with a focus on patients with moderate to severe plaque psoriasis who are candidates for systemic therapy. OBJECTIVES: To describe the baseline disease demographics and clinical characteristics of a Canadian subgroup of participants enrolled in PSOLAR. METHODS: Baseline demographic/disease characteristics, medical histories, and previous psoriasis treatments for Canadian patients in PSOLAR were summarized using descriptive statistics. RESULTS: There were 1896 patients analyzed in the Canadian subgroup at 37 clinical sites, accounting for 15.7% of the global PSOLAR population. Baseline disease and clinical characteristics were as expected for a moderate to severe psoriasis population and were generally similar to the global PSOLAR population. Two distinctions were noted in the Canadian subgroup versus those enrolled globally: a higher proportion of patients were overweight/obese (84.7% vs. 80.4%) and male (61.4% vs. 54.7%). In addition, the Canadian subgroup had numerically higher historical peak disease activity (PGA score 3.35 vs. 3.1) and longer disease duration (22.3 years vs. 17.5 years). Canadian PSOLAR patients reported a variety of comorbidities, including psoriatic arthritis (31.5%), hypertension (34.6%), hyperlipidemia (24.3%), mental illness (24.1%), and inflammatory bowel disease (1.6%). CONCLUSION: The Canadian subgroup of PSOLAR patients was generally similar to those enrolled globally with respect to baseline disease demographics and clinical characteristics. Multiple comorbidities are noted in the Canadian subgroup, underscoring the need for a holistic approach to the treatment of psoriatic patients.

Real-World Moderate-to-Severe Hidradenitis Suppurativa: Decrease in Disease Burden With Adalimumab.

BACKGROUND: Real-world knowledge of the burden of hidradenitis suppurativa (HS) on patients remains limited. OBJECTIVES: To measure the impact of adalimumab on moderate-to-severe HS patients' health-related quality of life (HRQoL) and work productivity. METHODS: In 23 Canadian centres, 138 adults with moderate-to-severe HS requiring a change in ongoing therapy were treated with adalimumab for up to 52 weeks as per the physician's practice. Patient-reported outcome measures (PROMs) were obtained at baseline, weeks 24 and 52 to measure overall HRQoL, HS severity, levels of anxiety and depression, impact and symptoms of HS, work productivity and activity impairment. A post-hoc analysis further explored the PROMs by abscess and inflammatory nodule (AN) count at baseline (≤5, low; 6-10, medium; ≥11, high). RESULTS: From baseline to weeks 24 and 52, all PRO overall scores improved significantly (P ≤ .0023). The number of patients reporting "good disease control" and "complete disease control" increased from 9.7% to 66.4% over 52 weeks. The score in Health Utility Index Mark 3 (HUI3) pain attribute meaningfully decreased over 52 weeks (mean difference ≥.05). The HS symptoms skin "tenderness" and "itchiness" improved the most. Work productivity loss and activity impairment improved by approximately 20% over 52 weeks. Disease burden improved more in 24 week responders with low and medium AN counts at baseline than in those with high AN count or in 24 week nonresponders. CONCLUSION: At week 24 and maintained at week 52 in a real-world setting, adalimumab meaningfully improved HRQoL, work productivity, and activity impairment in moderate-to-severe HS patients.

Clinical, patient and estimated cost benefits of proactive management versus reactive management with calcipotriol/betamethasone dipropionate foam for the treatment of plaque psoriasis in Finland.

BACKGROUND: Proactive management of plaque psoriasis with twice-weekly topical calcipotriol/betamethasone dipropionate (Cal/BD) foam has a demonstrated clinical benefit in preventing disease relapse compared to reactive management, where Cal/BD foam is only given as rescue therapy once-daily for four weeks after relapse. The impact of proactive management with Cal/BD foam on a wider range of clinical responses is not yet known, nor is its potential cost-effectiveness in the healthcare system of Finland. METHODS: This study involved a post-hoc analysis exploring the clinical and patient-reported benefits of proactive versus reactive management with Cal/BD foam observed in the PSO-LONG trial (NCT02899962). A range of response criteria based on modified psoriasis area and severity index (mPASI) and dermatology life quality index (DLQI) were analyzed, and the cost-effectiveness of proactive versus reactive management was estimated in a Finnish healthcare setting. RESULTS AND CONCLUSION: The analysis found a consistent clinical benefit of proactive management compared to reactive management on all response criteria, and a markedly lower cost-per-responder for the response criteria of mPASI 75, mPASI ≤ 2 and DLQ1 ≤ 1. The analysis was robust to sensitivity analyses on key inputs and demonstrates the cost and clinical benefits of proactive over reactive management of plaque psoriasis with Cal/BD foam in the Finnish healthcare setting.

Dermatologists' Perspectives on Defining Moderate Psoriasis: The Canadian Moderate Psoriasis Survey.

BACKGROUND: Psoriasis is commonly classified as either mild or moderate to severe, without specific parameters to differentiate moderate versus severe disease. This may lead to patients with moderate psoriasis being underrecognized and undertreated. OBJECTIVE: An online survey was conducted to assess Canadian dermatologists’ perspectives on the definition and treatment of psoriasis. METHOD: Dermatologists included in the survey were regional and national leaders with expertise in psoriasis. Questions were developed based on feedback from a steering committee of Canadian dermatologists. RESULTS: Of 88 dermatologists contacted, 69 responded; 42.0% were in practice for >20 years. Most dermatologists reported using the percentage of psoriasis-affected body surface area (BSA) to describe disease severity (90.8% for moderate and 87.5% for severe psoriasis). The lower and upper median cutoffs for moderate psoriasis were reported as 5.0% and 10.0% for BSA and 7.0 and 11.5 for the Dermatology Life Quality Index. Most dermatologists also consider psoriasis location (eg, palms, scalp, genital area, face) as an important indicator of disease severity. The majority of Canadian dermatologists (87.5%) identified access to treatment as one of the biggest challenges for patients with moderate psoriasis. Most dermatologists estimated that ≤40% of their patients with moderate plaque psoriasis were being treated with traditional oral systemics, targeted oral systemics, or biologics. CONCLUSIONS: This is the first survey of Canadian dermatologists on moderate psoriasis. Efforts are needed to implement a clinically useful definition of moderate plaque psoriasis to improve patient care and to raise awareness of the definition among regulatory agencies and reimbursement authorities. J Drugs Dermatol. 2021;20(2):126-132. doi:10.36849/JDD.5531.

Development and Content Validation of Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) in Adolescents and Adults with Moderate-to-Severe AD.

INTRODUCTION: Most patient-reported outcome (PRO) instruments that measure atopic dermatitis (AD) symptoms do not have sufficient documented evidence of content validity to satisfy regulatory agency guidance for inclusion in product-labelling claims in the USA or Europe. The objective of this study was to develop a PRO instrument in accordance with regulatory agency guidance to assess daily AD symptoms during the course of therapy and to establish its content validity and psychometric properties. METHODS: The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) daily diary was developed based on qualitative interviews with US adolescents and adults with mild-to-severe AD. Content validity, test-retest reliability, internal consistency reliability, clinically important difference, clinically important responder, convergent validity, and known-group validity were evaluated using correlational and regression methods from phase 2b data from US adults with moderate-to-severe AD who were treated with abrocitinib. RESULTS: Patient interviews conducted with US adolescents and adults with mild-to-severe AD identified 11 relevant symptoms (itch, dryness, redness, flaking, discolouration, pain, bleeding, cracking, bumps, swelling, and weeping/oozing) for inclusion in the PSAAD instrument. All PSAAD psychometric parameters were acceptable based on phase 2b data from US adults with moderate-to-severe AD. Convergent validity and known-group validity were confirmed by significant correlations between PSAAD and six other PRO measures (r = 0.24-0.91, all p ≤ 0.01) and Dermatology Life Quality Index category (p ≤ 0.0001), respectively. CONCLUSIONS: Evidence supports the PSAAD instrument validity, reliability, responsiveness and definitions of clinically important changes/differences for adults with moderate-to-severe AD.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document.

BACKGROUND:: Atopic dermatitis (AD) is a chronic, relapsing, and remitting inflammatory skin disease with complex pathophysiology, primarily driven by type 2 inflammation. Existing guidelines often do not reflect all current therapeutic options and guidance on the practical management of patients with AD is lacking. OBJECTIVES:: To develop practical, up-to-date guidance on the assessment and management of adult patients with AD. METHODS:: An expert panel of 17 Canadian experts, including 16 dermatologists and 1 allergist, with extensive clinical experience managing moderate-to-severe AD reviewed the available literature from the past 5 years using a defined list of key search terms. This literature, along with clinical expertise and opinion, was used to draft concise, clinically relevant reviews of the current literature. Based on these reviews, experts developed and voted on recommendations and statements to reflect the practical management of adult patients with AD as a guide for health care providers in Canada and across the globe, using a prespecified agreement cutoff of 75%. RESULTS:: Eleven consensus statements were approved by the expert panel and reflected 4 key domains: pathophysiology, assessment, comorbidities, and treatment. CONCLUSIONS:: These statements aim to provide a framework for the assessment and management of adult patients with AD and to guide health care providers in practically relevant aspects of patient management.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section III: Evaluation of Atopic Dermatitis Patients for Comorbidities.

Atopic dermatitis (AD) is often associated with other atopic diseases, including asthma, allergic rhinitis, atopy-associated eye disorders, and eosinophilic esophagitis. Depression and anxiety are also comorbidities to AD that significantly affect quality of life and should be screened for in patients with AD. Links to other comorbidities such as cardiovascular disease and malignancy are considered inconclusive, but patient counselling and screening may be appropriate in some patients. This article highlights practical recommendations for the recognition and management of atopic and nonatopic comorbidities commonly associated with AD.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section I: Pathophysiology of Atopic Dermatitis and Implications for Systemic Therapy.

Atopic dermatitis (AD) is a chronic, relapsing, and remitting inflammatory skin disease whose onset typically occurs early in life. AD pathophysiology includes genetic, immune, and environmental factors contributing to chronic inflammation. A rapidly evolving understanding of the pathogenesis of AD has led to the development of several treatment options for AD in adults, including topicals, phototherapy, and systemic therapies. Here, we provide a concise summary of AD pathophysiology with a focus on implications for systemic therapy.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section II: Tools for Assessing the Severity of Atopic Dermatitis.

Clinicians rely on clinical measures to define the severity of atopic dermatitis and assess outcomes of therapy. These measures can be objective (ie, physician assessments of disease severity) or subjective (ie, patient-reported symptoms and quality of life outcomes). In this review, the most commonly used tools for assessing atopic dermatitis severity in adult patients are presented and compared. These include Eczema Area and Severity Index (EASI); SCORing Atopic Dermatitis (SCORAD); Physician Global Assessment (PGA); body surface area (BSA); Atopic Dermatitis Severity Index (ADSI); Six Area, Six Sign Atopic Dermatitis (SASSAD); Patient Oriented Eczema Measure (POEM); Dermatology Life Quality Index (DLQI); and pruritus Numerical Rating Scale (NRS). Available severity strata for the tools are summarized, although the use of severity strata in clinical practice is not recommended. Since both objective and subjective assessments of disease severity are important to assess, consideration of clinical characteristics such as disease recurrence or persistence, as well as location of the affected areas, should be considered in the overall judgement of disease severity and consideration of therapy choice.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section V: Consensus Statements on the Assessment and Management of Adult Patients With Moderate-to-Severe Atopic Dermatitis.

This document is a concise, current, and practical guide for dermatologists and other health care providers managing adult patients with moderate-to-severe atopic dermatitis (AD). The recommendations made here are based on a consensus of specialists with extensive experience managing patients with AD. Topics reviewed in this publication include AD pathophysiology, assessment, comorbidities, and treatment options.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section IV: Treatment Options for the Management of Atopic Dermatitis.

The objectives of therapy for atopic dermatitis (AD) are to reduce skin inflammation and pruritus, restore skin barrier function, and improve quality of life (QoL). Treatments can be classified as moisturizing and basic care, topical therapy, phototherapy, and systemic therapy. In this review, we summarize the treatments for AD and recommendations for their use.

Depressive symptoms, depression, and the effect of biologic therapy among patients in Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: Patients with psoriasis are at an increased risk for depression. However, the impact of treatment on this risk is unclear. OBJECTIVE: Evaluate the incidence and impact of treatment on depression among patients with moderate-to-severe psoriasis. METHODS: We defined a study population within the Psoriasis Longitudinal Assessment and Registry and measured the incidence of depressive symptoms (Hospital Anxiety and Depression Scale-Depression score ≥8) and adverse events (AEs) of depression within cohorts receiving biologics, conventional systemic therapies, or phototherapy. Patients were evaluated at approximately 6-month intervals. Multivariate modeling determined the impact of treatment on risk. RESULTS: The incidence rates of depressive symptoms were 3.01 per 100 patient-years (PYs) (95% confidence interval [CI], 2.73-3.32), 5.85 per 100 PYs (95% CI, 4.29-7.97), and 5.70 per 100 PYs (95% CI, 4.58-7.10) for biologics, phototherapy, and conventional therapy, respectively. Compared with conventional therapy, biologics reduced the risk for depressive symptoms (hazard ratio, 0.76; 95% CI, 0.59-0.98), whereas phototherapy did not (hazard ratio, 1.05; 95% CI, 0.71-1.54). The incidence rates for AEs of depression were 0.21 per 100 PYs (95% CI, 0.15-0.31) for biologics, 0.55 per 100 PYs (95% CI, 0.21-1.47) for phototherapy, and 0.14 per 100 PYs (95% CI, 0.03-0.55) for conventional therapy; the fact that there were too few events (37 AEs) precluded modeling. LIMITATIONS: Incomplete capture of depression and confounders in the patients on registry. CONCLUSION: Compared with conventional therapy, biologics appear to be associated with a lower incidence of depressive symptoms among patients with psoriasis.

Efficacy and safety of ixekizumab for the treatment of moderate-to-severe plaque psoriasis: Results through 108 weeks of a randomized, controlled phase 3 clinical trial (UNCOVER-3).

BACKGROUND: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A, is efficacious in treating moderate-to-severe plaque psoriasis through 60 weeks. OBJECTIVE: To evaluate the efficacy and safety of ixekizumab through 108 weeks of treatment in UNCOVER-3. METHODS: Patients (N = 1346) were randomized 2:2:2:1 to 80 mg ixekizumab every 2 or 4 weeks, 50 mg etanercept twice weekly, or placebo. At week 12, patients switched to ixekizumab every 4 weeks during a long-term extension (LTE) period. Efficacy data were summarized using as-observed, multiple imputation (MI), and modified MI (mMI) methods. RESULTS: For patients (N = 385) receiving the recommended dose (ixekizumab every 2 weeks on weeks 0-12 and every 4 weeks during LTE), the 108-week as-observed, MI, and mMI response rates were 93.4%, 88.3%, and 83.6%, respectively, for patients achieving ≥75% improvement from baseline in the Psoriasis Area and Severity Index, and the 108-week as-observed, MI, and mMI response rates were 82.6%, 78.3%, and 74.1%, respectively, for patients with a static Physician's Global Assessment score of 0 or 1. During LTE, 1077 (84.5%) patients reported ≥1 treatment-emergent adverse event, and 85% were mild or moderate in severity. Discontinuation because of adverse events occurred in 6.4% of patients. LIMITATIONS: There was no comparison treatment group after week 12. CONCLUSION: Ixekizumab is well tolerated and demonstrates persistent efficacy through 108 weeks.