Filaggrin null mutations result in impaired skin barrier functions, increase the risk of early onset atopic dermatitis and lead to a more severe and chronic disease. We aimed to characterize the ...clinical presentation and course of atopic dermatitis associated with filaggrin mutations within the first 7 years of life.
The COPSAC cohort is a prospective, clinical birth cohort study of 411 children born to mothers with a history of asthma followed during their first 7 years of life with scheduled visits every 6 months, as well as visits for acute exacerbations of dermatitis. Atopic dermatitis was defined in accordance with international guidelines and described at every visit using 35 predefined localizations and 10 different characteristics.
A total of 170 (43%) of 397 Caucasian children developed atopic dermatitis. The R501X and/or 2282del4 filaggrin null mutations were present in 26 (15%) of children with atopic dermatitis and were primarily associated with predilection to exposed skin areas (especially the cheeks and back of the hands) and an up-regulation of both acute and chronic dermatitis. Furthermore, we found the filaggrin mutations to be associated with a higher number of unscheduled visits (3.6 vs. 2.7; p=0.04) and more severe (moderate-severe SCORAD 44% vs. 31%; p=0.14), and widespread dermatitis (10% vs. 6% of the body area, p<0.001) with an earlier age at onset (246 vs. 473 days, p<0.0001) compared to wild-type.
In children, filaggrin mutations seem to define a specific endotype of atopic dermatitis primarily characterized by predilection to exposed areas of the body, in particular hands and cheeks, and an up-regulation in both acute and chronic morphological markers. Secondary, this endotype is characterized by an early onset of dermatitis and a more severe course, with more generalized dermatitis resulting in more frequent medical consultations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and ...safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis.
In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index EASI score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 clear or 1 almost clear with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060.
Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 24% of 156 patients vs six 8% of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 44% of 153 patients vs six 8% of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 40% of 156 patients vs nine 12% of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 63% of 153 patients vs nine 12% of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported.
Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis.
Pfizer.
Background It is unclear whether patients with atopic dermatitis (AD) have an altered prevalence or risk for contact sensitization. Increased exposure to chemicals in topical products together with ...impaired skin barrier function suggest a higher risk, whereas the immune profile suggests a lower risk. Objective To perform a systematic review and meta-analysis of the association between AD and contact sensitization. Methods The PubMed/Medline, Embase, and Cochrane databases were searched for articles that reported on contact sensitization in individuals with and without AD. Results The literature search yielded 10,083 citations; 417 were selected based on title and abstract screening and 74 met inclusion criteria. In a pooled analysis, no significant difference in contact sensitization between AD and controls was evident (random effects model odds ratio OR = 0.891; 95% confidence interval CI = 0.771-1.03). There was a positive correlation in studies that compared AD patients with individuals from the general population (OR 1.50, 95% CI 1.23-1.93) but an inverse association when comparing with referred populations (OR 0.753, 95% CI 0.63-0.90). Limitations Included studies used different tools to diagnose AD and did not always provide information on current or past disease. Patch test allergens varied between studies. Conclusion No overall relationship between AD and contact sensitization was found. We recommend that clinicians consider patch testing AD patients when allergic contact dermatitis is suspected.
Atopic dermatitis (AD) has been associated with anxiety and depression, but the magnitude of the alleged association is unknown.
To perform a systematic review and meta-analysis of the association ...between AD in children and adults and, respectively, depression, anxiety, and suicidal behavior.
The medical databases PubMed, Embase, and PsychINFO were searched.
There was a significant association between adult AD and, respectively, depression (pooled odds ratio OR, 2.19; 95% confidence interval CI, 1.87-2.57) and anxiety (pooled OR, 2.19; 95% CI, 1.75-2.73). AD was also associated with depression in children (pooled OR, 1.27; 95% CI, 1.12-1.45); few data were available for anxiety. A positive association was found between AD in adults and adolescents and suicidal ideation (pooled OR, 4.32; 95% CI, 1.93-9.66). Only a few studies examined the risk of completed suicide, but the majority showed a positive association between completed suicide and AD.
Included studies used different definitions of depression and anxiety, and few studies examined the severity of AD.
Depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with AD. Because AD disease improvement appears to reduce these risks, this should be a priority.
Summary Background Phase 3 trials have assessed efficacy of abrocitinib versus placebo in moderate-to-severe atopic dermatitis, a common immunoinflammatory skin disease. This study assessed the ...efficacy and safety of abrocitinib versus dupilumab. Methods This randomised, double-blind, double-dummy, active-controlled, parallel-treatment, phase 3 trial enrolled adults with moderate-to-severe atopic dermatitis who requir=ed systemic therapy or had inadequate response to topical medications. Participants were enrolled from 151 sites, located in Australia, Bulgaria, Canada, Chile, Finland, Germany, Hungary, Italy, Latvia, Poland, Slovakia, South Korea, Spain, Taiwan, and the USA. These participants were then randomly assigned (1:1) with block randomisation to receive oral abrocitinib (200 mg per day) or subcutaneous dupilumab (300 mg every 2 weeks) for 26 weeks. Participants were required to apply topical corticosteroids (medium or low potency), topical calcineurin inhibitors, or a topical phosphodiesterase 4 inhibitor to active lesion areas. Primary endpoints were response based on achieving a 4 point or higher improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 2 and a 90% or better improvement in Eczema Area and Severity Index (EASI-90) at week 4. Family-wise type 1 error was controlled via a sequential multiple-testing procedure (two sided, α=0·05). Randomly assigned participants who received at least one dose of study intervention were included in the efficacy and safety analysis sets. This trial was completed on July 13, 2021 (NCT04345367). Findings Between June 11, 2020, and Dec 16, 2020, 940 patients were screened and 727 were enrolled (362 in the abrocitinib group and 365 in the dupilumab group). Compared with dupilumab, a larger proportion of patients treated with abrocitinib reached the primary outcomes, PP-NRS4 at week 2 (172 48% of 357, 95% CI 43·0–53·4 vs 93 26% of 364, 21·1–30·0; difference 22·6%, 15·8–29·5; p<0·0001), and EASI-90 at week 4 (101 29% of 354, 23·8–33·2 vs 53 15% of 364, 10·9–18·2; difference 14·1%, 8·2–20·0; p<0·0001). Treatment-emergent adverse events were reported by 268 (74%) of 362 patients treated with abrocitinib and by 239 (65%) of 365 patients treated with dupilumab. Two non-treatment-related deaths occurred in the abrocitinib group. Interpretation Abrocitinib 200 mg per day was more efficacious than dupilumab in adults with moderate-to-severe atopic dermatitis on background topical therapy in inducing early reductions of itch and atopic dermatitis disease signs. Both treatments were well tolerated over 26 weeks. Funding Pfizer.
Wide-ranging prevalence estimates of psoriatic arthritis (PsA) in patients with psoriasis have been reported.
To assess the prevalence and incidence of PsA in patients with psoriasis.
Two authors ...independently searched 3 databases for studies reporting on the prevalence or incidence of PsA in patients with psoriasis. A proportion meta-analysis was performed to calculate the pooled proportion estimates of PsA in patients with psoriasis.
A total of 266 studies examining 976,408 patients with psoriasis were included. Overall, the pooled proportion (95% confidence interval CI) of PsA among patients with psoriasis was 19.7% (95% CI, 18.5%-20.9%). In children and adolescents (<18 years of age), the pooled prevalence was 3.3% (95% CI, 2.1%-4.9%). The PsA prevalence was 22.7% (95% CI, 20.6%-25.0%) in European patients with psoriasis, 21.5% (95% CI, 15.4%-28.2%) in South American patients with psoriasis, 19.5% (95% CI, 17.1%-22.1%) in North American patients with psoriasis, 15.5% (95% CI, 0.009%-51.5%) in African patients with psoriasis, and 14.0% (95% CI, 95% CI, 11.7%-16.3%) in Asian patients with psoriasis. The prevalence of PsA was 23.8% (95% CI, 20.1%-27.6%) in studies in which the Classification Criteria for Psoriatic Arthritis were applied. The incidence of PsA among patients with psoriasis ranged from 0.27 to 2.7 per 100 person-years.
Between-study heterogeneity may have affected the estimates.
We found that 1 in 4 patients with psoriasis have PsA. With the growing recognition of the Classification Criteria for Psoriatic Arthritis, more homogenous and comparable prevalence estimates are expected to be reported.
Cause-specific mortality in adults with atopic dermatitis Thyssen, Jacob P.; Skov, Lone; Egeberg, Alexander
Journal of the American Academy of Dermatology,
March 2018, 2018-Mar, 2018-03-00, 20180301, Letnik:
78, Številka:
3
Journal Article
Recenzirano
Adult atopic dermatitis (AD) has been associated with several comorbidities, but cause-specific mortality risk is unknown.
To examine cause-specific death rates and risk in adults with AD.
We ...performed cross-linkage of nationwide health care and cause of death registers. Adult patients with AD were matched with 10 controls per study subject. We calculated incidence rates per 1000 person-years and hazard ratios (HRs) of cause-specific death with 95% confidence intervals (95% CIs) using Cox proportional hazards models.
A total of 8686 patients and 86,860 matched controls were studied. The risk for death due to any cause was significantly increased in patients with AD (HR 1.27, 95%CI 1.11-1.45). Significant causes included cardiovascular (HR 1.45; 95% CI 1.07-1.96), infectious (HR 3.71; 95% CI 1.43-9.60), and urogenital diseases (HR 5.51; 95% CI 1.54-19.80). No increased risk for death due to cancer, endocrine, neurologic, psychiatric, respiratory, or gastroenterologic disease was observed.
The results might not be generalizable to patients seen exclusively by primary care physicians.
Adults with atopic dermatitis had slightly increased risk for death during follow-up. While the risk for death from cardiovascular, urogenital, and infectious diseases was slightly elevated among patients with AD, the absolute risk was very low.
Atopic dermatitis (AD) is a common inflammatory skin disease characterized by intense pruritus and recurrent eczematous lesions that significantly impair quality of life. It is a heterogeneous ...disease affecting both children and adults. The treatment of moderate-to-severe forms of AD is challenging, as topical corticosteroids are often insufficient to achieve disease control or inappropriate and off-label use of immunosuppressants may have significant undesirable side effects. The development of targeted biologic therapies specifically for AD is thus highly desirable. Dupilumab is the only biologic therapy that is Food and Drug Administration approved for the treatment of moderate-to-severe AD in patients 6 years and older, with consistent long-term efficacy and safety trial data. In this article, we review the mechanisms, safety, and efficacy of dupilumab from recent clinical trials, and we review the current data, mechanism of action, clinical efficacy, and limitations of new biologics currently in phase 2 and 3 clinical trials (lebrikizumab, tralokinumab, nemolizumab, tezepelumab, and ISB 830).
The incidence and temporal trends of psoriasis in Denmark between 2003 and 2012 were examined. There was a female predominance ranging between 50.0% (2007) and 55.4% (2009), and the mean age at time ...of diagnosis was 47.7-58.7 years. A total of 126,055 patients with psoriasis (prevalence 2.2%) were identified. Incidence rates of psoriasis (per 100,000 person years) ranged from 107.5 in 2005 to a peak incidence of 199.5 in 2010. Incidence rates were higher for women, and patients aged 60-69 years, respectively. Use of systemic non-biologic agents, i.e. methotrexate, cyclosporine, retinoids, or psoralen plus ultraviolet A (PUVA) increased over the study course, and were used in 15.0% of all patients. Biologic agents (efalizumab, etanercept, infliximab, adalimumab, or ustekinumab) were utilized in 2.7% of patients. On a national level, incidence of psoriasis fluctuated during the 10-year study course. The relationship between psoriasis incidence and age appeared to be relatively linear, and disease prevalence was comparable to that in other European countries.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
Nickel contact allergy remains a problem in EU countries, despite the EU Nickel Directive. To study the prevalence of nickel allergy in EU countries following the implementation of the EU ...Nickel Directive, we performed a systematic search in PubMed for studies that examined the prevalence of nickel allergy in EU countries published during 2005–2016. We identified 46 studies: 10 in the general population and 36 in patch tested dermatitis patients. A significantly lower prevalence of nickel allergy after than before the implementation of the EU Nickel Directive was found in women aged 18–35 years (11.4% versus 19.8%) (p = 0.02), in female dermatitis patients aged ≤17 years (14.3% versus 29.2%) (p < 0.0001), and in dermatitis patients aged 18–30 years (women: 20.2% versus 36.6%) (p < 0.0001) (men: 4.9% versus 6.6%) (p < 0.0001). Overall, the prevalence was higher in southern than in northern EU countries, and generally remained high, affecting 8–18% of the general population. A consistent pattern of decreasing prevalence of nickel allergy in some EU countries was observed, although the prevalence among young women remains high. Steps should be taken for better prevention of nickel allergy in EU countries.
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