In two 16-week, placebo-controlled trials enrolling adults with moderate-to-severe atopic dermatitis, dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, was effective in ...controlling the signs and symptoms of atopic dermatitis.
Atopic dermatitis is a chronic, relapsing inflammatory skin disease that is characterized by the up-regulation of type 2 immune responses (including those involving type 2 helper T cells),
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an impaired skin barrier, and increased
Staphylococcus aureus
colonization.
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In patients with moderate-to-severe atopic dermatitis, skin lesions can encompass a large body-surface area and are frequently accompanied by intense, persistent pruritus, which leads to sleep deprivation, symptoms of anxiety or depression, and a poor quality of life.
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For patients with moderate-to-severe atopic dermatitis, topical therapies have limited efficacy, and systemic treatments are associated with substantial toxic effects. Thus, there . . .
•In this pooled analysis dupilumab significantly improved signs and symptoms of AD.•Dupilumab treatment alleviated pain/discomfort on the EuroQoL-5D.•Patient distribution within responder categories ...improved over time with dupilumab.•No new safety signals were observed with dupilumab.•Dupilumab had an overall favorable benefit-risk profile.
Two phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and LIBERTY AD SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in adults with moderate-to-severe atopic dermatitis (AD).
To report a pooled analysis of these trials to further explore dupilumab’s effects on AD clinical parameters, patient-reported outcomes (PROs), symptoms of anxiety/depression, health-related quality of life (HRQoL), and safety.
A pooled analysis of two 16-week phase 3 studies in adults with moderate-to-severe AD (N = 1379) inadequately controlled with/inadvisable for topical medications, randomized to dupilumab 300 mg once weekly (qw), every 2 weeks (q2w), or placebo.
Dupilumab significantly improved all pre-specified efficacy endpoints versus placebo (P < 0.0001), including clinical severity outcomes and PROs, symptoms of anxiety/depression, and HRQoL, consistent with previously published results. In post-hoc analyses, among patients reporting at least some baseline pain/discomfort on the EuroQoL-5D, no pain/discomfort at Week 16 was reported by 43%/46%/14% of dupilumab qw/q2w/placebo-treated patients (P < 0.0001). The distribution of dupilumab-treated patients within pre-defined score categories on the Investigator’s Global Assessment (0–1/2/3/4) and Eczema Area and Severity Index (≥90%/≥75–<90%/≥50–<75%/<50%) steadily and consistently improved over time versus marginal changes with placebo. Dupilumab significantly improved pruritus within 1–3 days of treatment initiation. No new safety signals were observed. Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbation and non-herpetic skin infections more frequent with placebo.
Dupilumab versus placebo significantly improved objective AD signs, subjective PROs, symptoms of anxiety/depression, and HRQoL, with a favorable benefit-risk profile in adults with moderate-to-severe AD.
A substantial part of ADHD treatment in Denmark is conducted by general practitioners and psychiatric specialists in private practice. ...we tracked dates of any filled ADHD medication prescriptions ...as a separate outcome. The data in the DNRP were reported to have a high positive predictive value for several disease diagnoses. ...any misclassification of AD would have been independent of future ADHD development.
Abstract Background Psoriasis and atopic dermatitis (AD) are immuno-inflammatory diseases that can result in lifelong systemic inflammation. Unlike AD, psoriasis has been associated with ...cardiovascular disease. The aim of this study was to examine the prevalence, severity, and subtype of coronary artery disease (CAD) in psoriasis and AD patients without known cardiovascular disease. Methods Consecutively enrolled patients (psoriasis n = 58, AD n = 31) and retrospectively matched controls (n = 33) were examined using cardiac computed tomography angiography (CCTA) and assessed using an 18-segment model of the coronary tree. Results The prevalence of a coronary artery calcium score >0 was 29.8% in psoriasis and 45.2% in AD, vs 15.2% in controls ( P = .09 and P = .01, respectively). More patients with psoriasis had a coronary artery calcium score ≥100 (psoriasis 19.3%, controls 2.9%; P = .02). CCTA showed the presence of plaques in 38.2% of psoriasis patients and 48.1% of AD patients, vs 21.2% of controls ( P = .08 and P = .03, respectively). Psoriasis was associated with an increased prevalence of significant coronary stenosis (stenosis >70%) (psoriasis 14.6%, controls 0%; P = .02) and 3-vessel coronary affection or left main artery disease (psoriasis 20%, controls 3%; P = .02), whereas AD was associated with mild (AD 40.7%, controls 9.1%; P = .005) single-vessel affection. Conclusions These findings suggest that psoriasis and AD are associated with an increased prevalence of CAD. Patients with psoriasis have an increased prevalence of severe CAD.
Atopic dermatitis (AD) is a common skin disease associated with a TH2 response and increased levels of TH2-associated cytokines and IgE. The mechanisms resulting in skewing the immune response in a ...TH2 direction in AD are not fully elucidated. However, such skewing has recently been associated with IL-25 in a murine model for allergic airway disease. The aim of this study was to investigate whether IL-25 may have a role in AD. We have identified IL-25-producing cells within the dermis of AD patients and propose that these cells are dendritic cells (DCs). This is supported by in vitro experiments that indicate that monocyte-derived DCs are capable of producing IL-25. As null mutations of filaggrin are associated with the development of an impaired skin barrier in AD, we investigated whether IL-25 affects filaggrin synthesis by keratinocytes. Using mRNA analysis, we have shown that IL-25 stimulation does indeed decrease filaggrin synthesis in cultured keratinocytes. These results suggest that IL-25 produced by DCs could have a dual role as both an inducer of the TH2 response and as an inhibitor of filaggrin synthesis, thereby directly affecting skin barrier function in AD patients.
Atopic dermatitis is a heterogeneous disease and resists classification. In this review, we discuss atopic dermatitis nomenclature and identify morphologic phenotypes, which will facilitate correct ...diagnoses and development of treatment strategies. We support using the term ‘atopic dermatitis’ rather than eczema, because it describes the allergic background and inflammation (‘itis’) as drivers of the disease. Atopic dermatitis has many morphologic manifestations that vary by topographic area affected, age, or race and require consideration in differential diagnosis. Different phenotypes based on morphology and topographic location, ethnicity, and age are discussed. A better-defined phenotype identification for atopic dermatitis will facilitate earlier and correct diagnosis of this complex condition and inform selection of the most appropriate treatment choice in an era in which targeted therapies may generate more individualized patient care.
Background
Patients with moderate-to-severe atopic dermatitis (AD) have increased infection risk, including skin infections and systemic infections. Immunomodulators (e.g., anti-tumor necrosis ...factors, anti-interleukin anti-IL-23, anti-IL-17, Janus kinase inhibitors) increase risk of infections. Dupilumab (a monoclonal antibody blocking the shared receptor component for IL-4 and IL-13) is approved for inadequately controlled moderate-to-severe AD and for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma.
Objective
The aim was to determine the impact of dupilumab on infection rates in patients with moderate-to-severe AD.
Methods
This analysis pooled data from seven randomized, placebo-controlled dupilumab trials in adults with moderate-to-severe AD. Exposure-adjusted analyses assessed infection rates.
Results
Of 2932 patients, 1091 received placebo, 1095 dupilumab 300 mg weekly, and 746 dupilumab 300 mg every 2 weeks. Treatment groups had similar infection rates overall per 100 patient-years (placebo, 155; dupilumab weekly, 150; dupilumab every 2 weeks, 156; dupilumab combined, 152), and similar non-skin infection rates. Serious/severe infections were reduced with dupilumab (risk ratio 0.43;
p
< 0.05), as were bacterial and other non-herpetic skin infections (risk ratio 0.44;
p
< 0.001). Although herpesviral infection rates overall were slightly higher with dupilumab than placebo, clinically important herpesviral infections (eczema herpeticum, herpes zoster) were less common with dupilumab (risk ratio 0.31;
p
< 0.01). Systemic anti-infective medication use was lower with dupilumab.
Conclusions
Dupilumab is associated with reduced risk of serious/severe infections and non-herpetic skin infections and does not increase overall infection rates versus placebo in patients with moderate-to-severe AD.
ClinicalTrials.gov Identifiers
NCT01548404, NCT02210780, NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649.
The aim of this appraisal of the literature is to elucidate the effects of immunosuppressive and immunomodulating agents used to treat atopic dermatitis (AD) on risk factors for fertility, pregnancy, ...and breastfeeding. Negative side effects of the psychological and physical stresses associated to AD flairs and uncontrolled AD are discussed, in order to evaluate the consequences of abstaining from treatment. Research on pregnancies in Danish women suggests a tendency towards an increased use of topical steroids and ultraviolet light therapy during pregnancy, compared to before conception, confirming the need for these patients to receive treatment, as well as decreased use of systemic treatments, suggesting a tendency towards undertreatment in this patient population. It is important that effective treatment be provided to pregnant women with AD. Here we present an appraisal of current knowledge on treatments for AD and the risks of exposure for the fetus and breastfed infant. Since little is known about the association between AD, pregnancy, and systemic treatment, we generalize conclusions based on studies on treatments of pregnant women who have undergone organ transplantation and who have inflammatory bowel disease, rheumatic disease, and autoimmune disease. The majority of recommendations are therefore based on a low or very low quality of evidence according to the GRADE system. The selected studies reflect the authors’ assessment regarding originality and importance in the context of this appraisal. It is always the treating doctor’s responsibility to stay updated on current literature when treating patients, especially pregnant patients.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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