Systemic Therapies For Atopic Dermatitis Research Articles

Retrospective evaluation of the effectiveness and safety of UVB-311 in atopic dermatitis

BACKGROUND: Atopic dermatitis is a widespread skin disease based on immune and genetic mechanisms of chronic inflammation formation. The disease most often develops in early childhood, has a frequent recurrent course, age-related clinical features. In this regard, the disease is characterized by a wide variety of treatment methods, the effectiveness of which varies and is a highly debated topic at the present time. AIM: to retrospectively evaluate the efficacy and safety of standard local and systemic therapy of atopic dermatitis in combination with UVB 311 nm. MATERIALS AND METHODS: 100 case histories of patients with atopic dermatitis of varying severity who were in the clinic of skin and venereal diseases in the period from 2022 to 2023 were analyzed. Of these, 50 patients received combined systemic and topical therapy with UVB 311 nm (the first group), and 50 patients received only standard topical and systemic therapy (the second group). Systemic and topical therapy of atopic dermatitis included, according to clinical recommendations, corticosteroids, calcineurin inhibitors, antihistamines. RESULTS: As a result of combined therapy with UVB 311 nm, patients showed a decrease in the SCORAD index by 1.7 times after 1 month of therapy, by 8 times after 2 months, and by 30 times after 6 months. In the second group, the SCORAD index decreased 1.2 times after 1 month from the start of therapy (p=0.0004), 3 times after 2 months (p=0.0001), 20 times after 6 months (p=0.003). Side effects in the first group were detected only in 5 (10%) patients: 2 (4%) patients had skin burning, 2 (4%) had skin itching, 1 (2%) patient had photodermatitis in the form of erythema of the skin. These adverse reactions were of a short-term nature and quickly passed if the recommendations were followed without canceling the procedures. CONCLUSION: UVB 311 nm therapy for atopic dermatitis has a higher therapeutic effect, is well tolerated, has minimal early side effects, and leads to clinical remission faster than standard systemic and local therapy.

Treatment of atopic dermatitis: Recently approved drugs and advanced clinical development programs.

Atopic dermatitis (AD) represents the most common skin disease characterized by heterogeneous endophenotypes and a high disease burden. In Europe, six new systemic therapies for AD have been approved: the biologics dupilumab (anti-interleukin-4 receptor (IL-4R) α in 2017), tralokinumab (anti-IL-13 in 2021), lebrikizumab (anti-IL-13 in 2023), and the oral janus kinase (JAK) inhibitors (JAKi) targeting JAK1/2 (baricitinib in 2020 in the EU) or JAK1 (upadacitinib in 2021 and abrocitinib in 2022). Herein, we give an update on new approvals, long-term safety, and efficacy. Upadacitinib and abrocitinib have the highest short-term efficacy among the approved systemic therapies. In responders, dupilumab and tralokinumab catch up regarding long-term efficacy and incremental clinical benefit within continuous use. Recently, the European Medicines Agency has released recommendations for the use of JAKi in patients at risk (cardiovascular and thromboembolic diseases, malignancies, (former) smoking, and age ≥65 years). Furthermore, we give an overview on emerging therapies currently in Phase III trials. Among the topical therapies, tapinarof (aryl hydrocarbon receptor), ruxolitinib (JAK1/2i), delgocitinib (pan-JAKi), asivatrep (anti-transient receptor potential vanilloid), and phosphodiesterase-4-inhibitors (roflumilast, difamilast) are discussed. Among systemic therapies, current data on cord-blood-derived mesenchymal stem cells, CM310 (anti IL-4Rα), nemolizumab (anti-IL-31RA), anti-OX40/OX40L-antibodies, neurokinin-receptor-1-antagonists, and difelikefalin (κ-opioid-R) are reported.

S3 guideline Atopic dermatitis: Part 2 - Systemic treatment.

The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups.

Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies

For people with atopic dermatitis (AD) refractory to topical therapies, treatment with phototherapy and systemic therapies can be considered. Multiple biologic therapies and Janus kinase (JAK)inhibitors have been approved since 2014 to treat AD. These guidelines update the 2014 recommendations for management of AD with phototherapy and systemic therapies. To provide evidence-based recommendations on the use of phototherapy and systemic therapies for AD in adults. A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of evidence and formulating and grading recommendations. The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic agents, including biologics, oral JAK inhibitors, and other immunomodulatory medications. Most randomized controlled trials of phototherapy and systemic therapies for AD are of short duration with subsequent extension studies, limiting comparative long-term efficacy and safety conclusions. We make strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. We make conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.

Unexpected Clinical Lessons Learned From IL-4 and IL-13 Blockade.

In 2017, dupilumab became the first FDA approved systemic therapy for atopic dermatitis. Since its approval, extensive clinical experience and continued research have revealed a number of unexpected effects that are highly clinically relevant. We will review these clinical effects and the supporting evidence.J Drugs Dermatol. 2023;22(10):1007-1008 doi:10.36849/JDD.7249.

Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique

This publication is an update of the “Consensus on the therapeutic management of atopic dermatitis – Brazilian Society of Dermatology” published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

426 Efficacy and safety of abrocitinib in adolescents with moderate-to-severe atopic dermatitis from the JADE clinical trial program

Abstract Once-daily oral abrocitinib, a Janus kinase 1-selective inhibitor, was effective and well tolerated as a monotherapy in adult and adolescent patients with moderate-to-severe atopic dermatitis (AD), as well as in combination with medicated topical therapy in adolescents with moderate-to-severe AD. This study aims to investigate efficacy and safety of abrocitinib in adolescents with moderate-to-severe AD from the JADE clinical trial program. Patients aged 12–17 years with moderate-to-severe AD and an inadequate response to ≥4 consecutive weeks of topical medication or treatment with systemic therapy for AD, both within the past 6 months, were randomly assigned [2:2:1 JADE MONO-1/MONO-2 (NCT03349060/NCT03575871); 1:1:1 JADE TEEN (NCT03796676)] to receive once-daily oral abrocitinib (200 or 100 mg) or placebo as monotherapy (JADE MONO-1 and JADE MONO-2) or in combination with medicated topical therapy (JADE TEEN) for 12 weeks. Coprimary endpoints were proportion of patients achieving Investigator’s Global Assessment (IGA) response [clear (0) or almost clear (1) with ≥2-grade improvement from baseline] and proportion of patients who achieved ≥75% improvement in Eczema Area and Severity Index score (EASI-75) at Week 12. A key secondary endpoint was the proportion of patients achieving ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4; used with permission from Regeneron Pharmaceuticals and Sanofi) at Week 12. Drug safety was also assessed. Overall, 285 and 124 adolescents in JADE TEEN and JADE MONO-1/MONO-2, respectively, were treated. In JADE TEEN, more abrocitinib-treated (200 mg, 100 mg) than placebo-treated patients achieved IGA (46.2%, 41.6% vs. 24.5%; P < 0.05 for both doses), EASI-75 (72.0%, 68.5% vs. 41.5%; P < 0.05 for both doses) and PP-NRS4 (55.4%, 52.6% vs. 29.8%; P < 0.01 for 200 mg vs. placebo) responses at Week 12. Adverse events (AEs) were reported for 62.8%, 56.8% and 52.1% of patients in 200 mg, 100 mg and placebo groups, respectively; 1 (1.1%), 0 and 2 patients (2.1%) had serious AEs. JADE MONO-1/MONO-2 safety results were similar, but efficacy results were lower, as expected for monotherapies. Results from JADE clinical trials suggest that abrocitinib was effective in adolescents with moderate-to-severe AD, with an acceptable safety profile.

Застосування емолієнтів при атопічному дерматиті в дітей (огляд літератури)

Modern external pharmacotherapy of atopic dermatitis in children should be etiopathogenetic and effects on the mechanisms of formation of allergic inflammation. External therapy of atopic dermatitis in children consists in the local application of emollients, glucocorticosteroids, antileukotriene, antihistamine medications, topical calcineurin inhibitors, in the case of complicated forms - antibacterial, antifungal, antiviral medications along with skin care. Eliminating dryness of the skin is the most important part of the external therapy of atopic dermatitis. Emollients are the main agents of the basic external therapy of atopic dermatitis, which perform the role of restoring and protecting the stratum corneum of the epidermis, maintaining hydro-lipid balance and preventing transepidermal water loss, reduce dryness, itching and peeling, have a glucocorticoid-saving effect, are used to achieve and maintain control over the symptoms of the disease. Emollients contain lipids and work through occlusion, trapping natural moisture in the skin, and/or through the properties of a humectant component that draws water from the dermis into the epidermis. Emollients are combined with local and systemic therapy of atopic dermatitis of any degree of severity, it should be used independently in the period of remission, increasing the duration of remission and preventing relapses. Purpose - to increase the awareness of doctors and patients about the current features of the use of emollients in atopic dermatitis in children. The use of emollients together with hydration and cleaning of the skin contributes to the restoration and preservation of a skin barrier function, reduces susceptibility to irritants and allergens. Emollients soften, smooth and rehydrate the skin, which helps to reduce unpleasant sensations, dryness, itching, inflammation at atopic dermatitis in children. A wide range of dosage forms of emollients, including cleansing agents for washing (gels, foams/mousses, soaps, solutions), as well as non-rinsable agents (lotions, creams, ointments, oils, emulsions), makes this group of medications available for a large number of patients with various clinical situations. Emollients can be used independently, as well as as adjuvant therapy with other topical or systemic agents at atopic dermatitis in children. The effective use of emollients improves the condition of the skin and has a positive effect on the quality of life. No conflict of interests was declared by the authors.

Expert consensus on the systemic treatment of atopic dermatitis inspecial populations.

With the increasing number of options for the treatment of moderate-to-severe atopic dermatitis, clinicians need guidance on a practical approach to selecting a systemic agent for specific patient populations. We convened an expert panel consisting of 12 members to conduct a literature review and summarize relevant data related to six scenarios of clinical interest: comorbid asthma, ocular surface disease, history of cancer, past and ongoing infections of interest (including herpes simplex virus, herpes zoster, hepatitis B, and tuberculosis), pregnancy and lactation, and the elderly. We performed a literature search and examined each clinical scenario with respect to three major categories of available systemic agents: traditional systemics (azathioprine, cyclosporine A, methotrexate, and mycophenolate mofetil), Janus kinase inhibitors (abrocitinib, baricitinib, and upadacitinib), and biologics (dupilumab, lebrikizumab, and tralokinumab). The expert panel and steering committee met virtually to review the data and discuss the drafted consensus statements. A modified Delphi process was used to arrive at a set of final consensus statements related to the systemic treatment of AD in these specific patient populations. To provide practical guidance on the choice of systemic therapy for atopic dermatitis in these six topics of clinical interest, 25 expert consensus statements and a summary of the supporting data are presented herein.

327 Optimizing the management of atopic dermatitis with a new minimal disease activity concept and criteria and consensus-based recommendations for systemic therapy

Abstract Inconsistent criteria are used to identify patients with atopic dermatitis (AD) who are candidates for systemic therapy and assess their response to systemic therapy. This may lead to undertreatment and treatment dissatisfaction. A treat-to-target (T2T) framework was previously proposed to guide systemic treatment decisions in patients with moderate-to-severe AD.1 While patient representatives were included in the T2T consensus voting process, no patient or caregiver stakeholders were included in the development of the T2T recommendations. Additionally, a recent analysis of the cross-sectional, 28-country MEASURE-AD study suggests that the treatment targets in the T2T criteria may be insufficient to ensure optimal treatment outcomes.2 To develop optimized and practical criteria for identifying patients who should receive systemic therapy, including definitions of treatment goals, treatment failure and disease severity. An executive steering committee (ESC) of seven international experts was formed in January 2021 to provide insights and perspectives on how to optimize the identification of patients who would most benefit from systemic therapy for AD. After discussing the gaps and needs in current AD management, the ESC agreed that there was a lack of evidence on patients’ treatment goals, needs, and expectations. The ESC, therefore, initiated a global, ethically and culturally diverse patient research study (N = 88) to collect these insights. Subsequently, nine regional sub-committees (SCs) were created to gain clinical perspectives from different regions worldwide (covering the USA and Puerto Rico, Latin America, Western Europe and Canada, Eastern Europe and Russia, the Middle East, Asia, and Australia and New Zealand). Overall, 87 experts from 44 countries contributed to the initiative, and 46 virtual ESC and SC meetings took place to discuss how to improve the lives of patients with AD. A virtual secure platform allowed discussions and contributions to continue outside these meetings. In April 2022, all experts rated their agreement with a series of recommendations regarding the identification and monitoring of patients eligible for systemic therapy, using a 10-point Likert scale in a modified eDelphi voting process. The consensus was pre-defined as ≥70% of all respondents rating agreement as 7 (‘mildly agree’), 8 (‘moderately agree’), 9 (‘agree’) or 10 (‘strongly agree’) with a recommendation. A strong consensus was defined as ≥90% agreement. Expert perspectives and patient insights led to the development of 34 patient-focused clinical recommendations on disease severity assessments, treatment goals and targets for clinician- and patient-reported outcomes, long-term disease control and a novel minimal disease activity (MDA) concept. A consensus of ≥80% was reached for all recommendations in one round of voting, with 88% of the recommendations reaching a ‘strong’ consensus. The MDA concept combines T2T principles with shared patient/clinician treatment decision-making principles. Patients are asked to select 1–3 feature(s) of AD which are most important to them (from the itch, skin appearance/condition, sleep disturbance, mental health, skin pain and impact on daily life). The clinician is asked to choose an objective measure of disease (from the Eczema Area and Severity Index [EASI], SCORing AD and/or the Investigator’s Global Assessment and body surface area). Treatment targets are then chosen from a list of ‘moderate’ and ‘optimal’ targets based on discussions between the clinician and patient. Optimal treatment targets include ≥90% improvement in EASI and a numeric rating scale of ≤ 1 for peak pruritus, sleep, and pain. Achievement of ‘optimal’ targets is defined as MDA. This international group of AD experts developed a novel MDA concept and criteria, which builds upon existing T2T work by providing a patient-centric approach to the optimal treatment of AD. The criteria and patient-focused clinical recommendations will help to identify and monitor patients with AD who could benefit from systemic therapy.

JAK Inhibitor Safety Compared to Traditional Systemic Immunosuppressive Therapies.

Dermatologists treating atopic dermatitis are interested in the safety profile of the recently available JAK inhibitors, upadacitinib and abrocitinib, especially after they received boxed safety warnings. Long-term clinical trial data using these JAK inhibitors for the treatment of atopic dermatitis suggest that they are associated with very low incidence rates of malignancy, major adverse cardiac events, and thromboembolic events. However, a knowledge gap exists regarding the incidence of adverse events for JAK inhibitors compared to traditional systemic therapies used to treat poorly controlled atopic dermatitis as well as baseline rates in both atopic dermatitis and reference control populations. To address this gap, we analyzed data regarding adverse events of special interest for methotrexate, cyclosporine, and systemic corticosteroids and calculated the incidence of adverse events per 100 patient-years for these drugs. We also examined data regarding baseline incidence of adverse events in atopic dermatitis and control patients. We found that compared to upadacitinib and abrocitinib, traditional systemic therapies for atopic dermatitis demonstrated equal or higher incidence rates for malignancy (excluding non-melanoma skin cancer), non-melanoma skin cancer, major adverse cardiac events, and venous thromboembolism. Moreover, the use of upadacitinib and abrocitinib also exhibited either comparable or lower incidence of malignancy (excluding non-melanoma skin cancer), major adverse cardiac events, and venous thromboembolism, but higher rates of non-melanoma skin cancer, in comparison to baseline rates in atopic dermatitis or control patients. These findings indicate that JAK inhibitors should be positioned, at least based on safety, ahead of traditional systemic therapies for atopic dermatitis treatment.J Drugs Dermatol. 2022;21(12):1298-1303. doi:10.36849/JDD.7187.

34574 Systemic medication treatment patterns in adults with atopic dermatitis (AD): Results from the European Prospective Observational Study in Patients Eligible for Systemic Therapy for Atopic Dermatitis (EUROSTAD)

Introduction: EUROSTAD (OBS14620) is an observational study of up to 60 months to characterize AD treatment in a real-world setting. Here, we describe systemic treatment-patterns in patients enrolled in EUROSTAD. Methods: Individuals with AD, ≥18 years old and eligible for systemic treatment, were enrolled. Initial study period was 18 months but was amended to 60 months. Treatment was prescribed by study investigators as per clinical practice. Follow-up population is defined as all patients who have completed ≥1 follow-up visit. Reported data is descriptive from the full-analysis set at 24 months. Results: 308 patients were enrolled (mean AD duration: 25.4 years). Most patients reported ≥1 systemic medication use at enrollment (92.5%). During follow-up (n = 295) most patients reported using either one (56.3%) or >1 (41.4%) systemic medication. Cyclosporin, dupilumab, corticosteroids and methotrexate were the most common systemic therapies. Most common reasons reported for treatment initiation were maintenance and exacerbation treatment (both 79.7%), while well-controlled disease (59.7%) and lack of efficacy (38.1%) were the most common reasons for discontinuation. Median duration of systemic treatment was between 1.1-13 months for the most common therapies (corticosteroids, 1.1 months (95% CI 1.0-1.5); cyclosporin, 5.4 months (4.2-6.6), methotrexate, 13.0 months [8.9-16.9]); median duration of dupilumab treatment was not reached because >50% of patients were still on dupilumab at 24 months. Conclusion: AD therapy was started for exacerbation or maintenance treatment and discontinued mainly due to lack of efficacy or well-controlled disease. Patients who initiated dupilumab were more likely to remain on dupilumab compared with other systemic therapies.

Real-World Effectiveness of Newly Initiated Systemic Therapy for Atopic Dermatitis in the United States: A Claims Database Analysis

IntroductionAtopic dermatitis (AD) is associated with significant quality-of-life and economic burdens. Real-world evidence is needed to identify optimal treatment pathways for AD. Here we evaluate real-world effectiveness of systemic therapies for moderate-to-severe AD in the USA.MethodsData (September 2016 to December 2019) were from the IQVIA Health Plan Claims data set (IQVIA, Danbury, CT) from patients aged 12 years or older with AD (ICD-9/10-CM, 691.8/L20.x) initiating a systemic immunosuppressive (SIS) agent (methotrexate, cyclosporine, mycophenolate, or azathioprine) or dupilumab and continuously enrolled for at least 6 months before and after the index date. Indicators of non-response (i.e., adding on/switching systemic therapy, AD-related inpatient/emergency room visits, or incident staphylococcal/streptococcal skin infection) and predictors of non-response were evaluated. Descriptive statistics and Kaplan–Meier rates and times were obtained; Cox regression models were used.ResultsIn 3249 patients, 45.4% exhibited at least one indicator of non-response, with median time to non-response being longer for dupilumab than for any SIS therapy (27.0 vs 4.0–7.7 months, respectively). Key non-response predictors were age, geographic region, and baseline number of annual AD-related medical visits.ConclusionNon-response was common in patients with AD who required systemic treatment, and non-response indicators occurred significantly more frequently with SIS treatment than with dupilumab treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02197-z.

Resolution of the Working Meeting of Experts in “Dermatology”: Possibilities of systemic therapy of atopic dermatitis with selective immunosuppressants

On February 19, 2022, a working meeting of experts on the problem of atopic dermatitis was held in Moscow under the chairmanship of the Director of the State Scientific Center for Dermatovenereology and Cosmetology of the Ministry of Health of Russia, Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Sciences A.A. Kubanov. Also in attendance was the Academician of the Russian Academy of Sciences, Chief Freelance Childrens Specialist in Preventive Medicine, Head of the Research Institute of Pediatrics and Childrens Health of the Central Clinical Hospital of the Russian Academy of Sciences of the Ministry of Science, and Higher Education of the Russian Federation, Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, L.S. Namazova-Baranova, and also the Deputy Director for Clinical Work ― Chief Physician of the Federal State Budgetary Institution SSC Institute of Immunology FMBA of Russia Doctor of Medical Sciences, Professor N.I. Ilyina.
 The meeting raised germane issues of providing medical care, reducing the burden of the disease, and improving the quality of life of patients with atopic dermatitis. New possibilities and principles of systemic therapy in patients with moderate and severe atopic dermatitis were discussed. We analyzed data on a new representative of the small molecule class the selective Janus kinase 1 inhibitor, upadacitinib, which was registered in the Russian Federation in June 2021. This analysis aimed to determine its place in atopic dermatitis therapy algorithms and the possibility of the impact of its use as a therapy on the quality of life of patients in relation to the burden of diseases.
 The article has been published in several journals simultaneously with permission from authors and publishers. The parallel publication is available here: Capabilities of atopic dermatitis systemic therapy with selective immunosuppressors: resolution of the experts workshop of dermatology profile. Pediatric pharmacology. 2022;19(2):209211. DOI: https://doi.org/10.15690/pf.v19i2.2424

[Modern systemic therapies for atopic dermatitis : Which factors determine the choice of therapy?]

For the treatment of moderate to severe atopic dermatitis (AD), two groups of modern systemic therapies with atotal of five drugs are currently approved in Germany: biologics (dupilumab, tralokinumab) and "small molecules" (abrocitinib, baricitinib, upadacitinib). The growing armamentarium of therapy options, especially with more than one drug per substance group, makes it challenging for practitioners to select the appropriate treatment for the individual patient. In this review article, the preconditions and requirements of each drug group as well as the corresponding substances are presented comparatively. On the one hand, direct therapeutic effects on the severity of the disease are considered and, on the other hand, the spectrum of potential adverse drug reactions are discussed. In particular, short- and long-term effects, the safety profile and the patient's concomitant diseases represent key factors for shared decision-making with regard to select the optimum personalized therapy option.

Systemic Therapy for Atopic Dermatitis in Older Adults and Adults With Comorbidities: A Scoping Review and International Eczema Council Survey.

BackgroundClinical trials of systemic therapies for atopic dermatitis (AD) often exclude patients based on age and comorbidities.ObjectivesWe conducted a scoping review of observational studies and survey of International Eczema Council (IEC) members on the treatment of AD in patients with liver disease, renal disease, viral hepatitis, HIV, or history of malignancy.MethodsWe searched MEDLINE via Ovid, Embase via Ovid, and Web of Science from inception to September 14, 2020. We mapped the available evidence on the use of cyclosporine, methotrexate, azathioprine, mycophenolate, systemic corticosteroids, and dupilumab for AD in older adults (≥65 years) and adults with the previously mentioned comorbidities. We surveyed IEC members on their preferred systemic medications for each patient population.ResultsWe identified 25 studies on the use of systemic medications in special populations of adults with AD. Although IEC members preferred dupilumab as the first-line systemic agent across all special populations, many could not identify viable third-line systemic therapy options for some populations.ConclusionsData on systemic therapy for AD for older adults and adults with comorbidities are limited. Although IEC members' access to systemic therapies differs geographically, expert opinion suggests that dupilumab is preferred for those patients.

Use of systemic therapies in adults with atopic dermatitis: 12-month results from the European prospective observational study in patients eligible for systemic therapy for atopic dermatitis (EUROSTAD)

Background The European Prospective Observational Study in Patients Eligible for Systemic Therapy for Atopic Dermatitis (EUROSTAD) is an ongoing observational study aiming to describe characteristics of patients with atopic dermatitis (AD) treated with systemic therapy over time and the management of their disease in a real-world setting. Methods Data from patients enrolled in EUROSTAD between March 2017 and April 2019 were analyzed for systemic therapy use and treatment change over 12 months. Results 288 patients reported taking systemic medications; 42.7% received cyclosporine, 35.3% dupilumab, 28.1% methotrexate, 25.4% oral corticosteroids, 6.8% azathioprine, 6.1% injectable corticosteroids, and 3.4% mycophenolate. The median duration of treatment was 1.1 months for oral systemic corticosteroids, 3.2 months for injectable corticosteroids, 4.8 months for cyclosporine, 7.3 months for methotrexate, and 14.9 months for dupilumab. The most frequent reasons for stopping treatment included lack of efficacy, patient decision, adverse events, and disease well controlled. Conclusion The 12-month interim EUROSTAD study analysis highlights the current trends and outcomes of systemic treatments for moderate-to-severe AD. Among all systemic treatments for AD, dupilumab was the least likely to be discontinued, whereas cyclosporine and corticosteroids, whilst effective, were primarily limited to episodic flare management consistent with treatment guidelines.

Impact of oral abrocitinib on signs, symptoms and quality of life among adolescents with moderate‐to‐severe atopic dermatitis: an analysis of patient‐reported outcomes

BackgroundA significant improvement in clinical signs was demonstrated with abrocitinib relative to placebo in adolescents with moderate‐to‐severe atopic dermatitis (AD) in three phase 3, randomized, double‐blinded, placebo‐controlled studies (JADE TEEN [ClinicalTrials.gov, NCT03796676], JADE MONO‐1 [NCT03349060] and JADE MONO‐2 [NCT03575871]).ObjectivesTo evaluate the impact of abrocitinib on patient‐reported signs/symptoms, including sleep loss and quality of life among adolescents with moderate‐to‐severe AD.MethodsJADE TEEN, JADE MONO‐1 and JADE MONO‐2 were conducted in the Asia‐Pacific region, Europe and North America and included patients aged 12–17 years with moderate‐to‐severe AD and inadequate response to ≥ 4 consecutive weeks of topical medication or treatment with systemic therapy for AD. Patients were randomly assigned (1 : 1 : 1, JADE TEEN; 2 : 2 : 1, JADE MONO‐1/‐2) to receive once‐daily oral abrocitinib (200 or 100 mg) or placebo for 12 weeks in combination with topical therapy (JADE TEEN) or as monotherapy (JADE MONO‐1/‐2). Data from adolescent patients in JADE MONO‐1/‐2 were pooled for these analyses.ResultsAt week 12, more adolescents treated with abrocitinib (200 or 100 mg) vs. placebo achieved a ≥ 4‐point improvement from baseline in the Patient‐Oriented Eczema Measure in JADE TEEN (83.9% and 77.0% vs. 60.2%) and JADE MONO‐1/‐2 (83.0% and 69.4% vs. 43.5%) and a ≥ 6‐point improvement from baseline in the Children’s Dermatology Life Quality Index in JADE TEEN (73.8% and 67.5% vs. 56.5%) and JADE MONO‐1/‐2 (70.0% and 57.1% vs. 19.0%). Significant improvements in SCORing Atopic Dermatitis Visual Analog Scale for sleep loss scores were demonstrated with abrocitinib vs. placebo at weeks 2‐12 in JADE TEEN and JADE MONO‐1/‐2.ConclusionsPatient‐reported signs/symptoms, including reduction of sleep loss and quality of life, were substantially improved with abrocitinib monotherapy or combination therapy relative to placebo in adolescents with moderate‐to‐severe AD.

Novel agents for atopic dermatitis in patients over 50 years of age: A case series.

Lan et al recently highlighted the under-representation of older adults in clinical trials of systemic therapies for atopic dermatitis (AD). Late-onset AD is increasingly recognized in older adults. Spontaneous remission is uncommon with this phenotype. Existing drug treatments such as corticosteroids, methotrexate, ciclosporin, and azathioprine are complicated by adverse effects including increased malignancy risk, immunosuppression in the context of immunosenescence, and drug interactions in the setting of polypharmacy. A case series is presented of seven patients over 50 years of age with AD who were prescribed dupilumab or tofacitinib or upadacitinib for at least 6 months. All patients were clear or almost clear (investigator global assessment score 0/1) after 1 month of therapy. No significant adverse events were seen. This case series provides preliminary evidence about the safety and efficacy of these novel drugs for AD in older adults. Further studies with higher numbers of participants are needed to obtain real-world evidence for these drugs in older adults, given the limited data in clinical trials.

Real-World Effectiveness of Systemic Therapies for Atopic Dermatitis (AD) in the United States: Analysis of a Retrospective Claims Database

Real-World Effectiveness of Systemic Therapies for Atopic Dermatitis (AD) in the United States: Analysis of a Retrospective Claims Database