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Health Technology Assessment... Jan 2024Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the age of 5 years, but it can develop at any age. Atopic dermatitis is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus).
OBJECTIVES
To appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe atopic dermatitis compared to systemic immunosuppressants (first-line ciclosporin A or second-line dupilumab and baricitinib).
DATA SOURCES
Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence provided by the sponsoring companies of the treatments under review.
METHODS
A systematic review of the clinical effectiveness literature was carried out and a network meta-analysis undertaken for adults and adolescents at different steps of the treatment pathway. The primary outcome of interest was a combined response of Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4; where this was consistently unavailable for a step in the pathway, an analysis of Eczema Area and Severity Index 75 was conducted. A de novo economic model was developed to assess cost effectiveness from the perspective of the National Health Service in England. The model structure was informed through systematic review of the economic literature and by consulting clinical experts. Effectiveness data were obtained from the network meta-analysis. Costs and utilities were obtained from the evidence provided by sponsoring companies and standard UK sources.
RESULTS
Network meta-analyses indicate that abrocitinib 200 mg and upadacitinib 30 mg may be more effective, and tralokinumab may be less effective than dupilumab and baricitinib as second-line systemic therapies. Abrocitinib 100 mg and upadacitinib 15 mg have a more similar effectiveness to dupilumab. Upadacitinib 30 and 15 mg are likely to be more effective than ciclosporin A as a first-line therapy. Upadacitinib 15 mg, abrocitinib 200 and 100 mg may be more effective than dupilumab in adolescents. The cost effectiveness of abrocitinib and upadacitinib for both doses is dependent on the subgroup of interest. Tralokinumab can be considered cost-effective as a second-line systemic therapy owing to greater cost savings per quality-adjusted life-year lost.
CONCLUSIONS
The primary strength of the analysis of the three new drugs compared with current practice for each of the subpopulations is the consistent approach to the assessment of clinical and cost effectiveness. However, the conclusions are limited by the high uncertainty around the clinical effectiveness and lack of data for the primary outcome for comparisons with baricitinib and for the adolescent and adult first-line populations.
FUTURE WORK AND LIMITATIONS
The most significant limitation that Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4 could not be obtained for the adolescent and adult first-line systemic treatment populations is due to a paucity of data for dupilumab and ciclosporin A. A comparison of the new drugs against one another in addition to current practice would be beneficial to provide a robust view on which treatments are the most cost-effective.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42021266219.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135138) and is published in full in ; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information.
Topics: Child; Adult; Adolescent; Humans; Child, Preschool; Dermatitis, Atopic; Cyclosporine; State Medicine; Treatment Outcome; Cost-Benefit Analysis; Eczema; Antibodies, Monoclonal; Purines; Heterocyclic Compounds, 3-Ring; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38343072
DOI: 10.3310/LEXB9006 -
Allergy, Asthma, and Clinical... Sep 2021Atopic dermatitis is the most common chronic inflammatory skin disease and presents a major public health burden worldwide. Recent observational studies revealed the... (Review)
Review
BACKGROUND
Atopic dermatitis is the most common chronic inflammatory skin disease and presents a major public health burden worldwide. Recent observational studies revealed the potential association between atopic dermatitis with autoimmune disorders. However, there is no meta-analysis of the prevalence or incidence of autoimmune diseases in atopic dermatitis. Therefore, considering the potential clinical implications of these associations, we aimed to assess the risk of autoimmune diseases in patients with atopic dermatitis using this method.
METHODS
PubMed, Embase, and Web of Science were searched from inception to October, 2020. Observational studies which provided estimate effects with 95% CI or raw data were included. The quality of selected studies was evaluated using the Newcastle-Ottawa Scale. Odds ratio and relative risks were pooled using a random effects model and expressed with 95% confidence intervals.
RESULTS
Fourteen observational studies were included in this systematic review and meta-analysis. The random-effects meta-analysis of case-control and cross-sectional studies showed a significant association of atopic dermatitis with mutiple autoimmune diseases, including alopecia areata, celiac disease, Crohn's disease, rheumatoid arthritis, systematic lupus erythematosus, ulcerative colitis and vitiligo. Furthermore, pooling of the results of cohort studies showed that patients with atopic dermatitis were more likely to develop these autoimmune diseases.
CONCLUSION
Our meta-analysis showed that patients with atopic dermatitis were at higher risk of multiple autoimmune diseases including alopecia areata, celiac disease, Crohn's disease, rheumatoid arthritis, systematic lupus erythematosus, ulcerative colitis and vitiligo. It is important for early detection of the affected group so that timely management can be initiated. Dermatologists and allergists should be aware of the autoimmune diseases in patients with atopic dermatitis and develop interventions if necessary. Also, limited by the present research, we still require more large-scale studies to further establish the association between atopic dermatitis and autoimmune diseases.
PubMed: 34563251
DOI: 10.1186/s13223-021-00597-4 -
Photodermatology, Photoimmunology &... May 2022Phototherapies could represent an efficient option for the treatment of atopic dermatitis (AD), but the evidences available for clinical choices were contradictory. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Phototherapies could represent an efficient option for the treatment of atopic dermatitis (AD), but the evidences available for clinical choices were contradictory.
OBJECTIVE
This study aimed to evaluate the efficacy of different phototherapies on AD.
METHODS
This systematic review and network meta-analysis included randomized controlled trials (RCTs) through searching keywords from PubMed, EMBASE, and the Cochrane library. We summarized different phototherapy types and scoring systems. Scoring Atopic Dermatitis (SCORAD) absolute score changes were estimated by mean differences (MDs) and standard deviations (SDs) and then included in the network meta-analysis. The effect sizes of comparison of different phototherapies were presented as MDs and 95% confidence intervals (CIs). Egger's test was used to evaluate publication bias.
RESULTS
Eleven RCTs were included in the systematic review and 4 studies in the network meta-analysis. Based on the pooled estimates, medium-dose ultraviolet A1 (UVA1) cold light was superior to medium-dose UVA1 (MD 8.92; 95% CI: 5.60-12.24) but no significant difference between high-dose (UVA1) and medium-dose UVA1 cold light (MD 0.66; 95% CI: -5.57 to 6.90). Publication bias was not supported by Egger's test (P = .168).
CONCLUSIONS
Due to possible long-term adverse effects of high-dose UVA1, medium-dose UVA1 cold light appears to be the superior form for AD.
Topics: Dermatitis, Atopic; Humans; Network Meta-Analysis; Phototherapy; Randomized Controlled Trials as Topic; Treatment Outcome; Ultraviolet Therapy
PubMed: 34653289
DOI: 10.1111/phpp.12741 -
Journal of the American Academy of... Jan 2021Dupilumab, the first biological drug to be approved for the treatment of moderate to severe atopic dermatitis in adolescents and adults, has shown good efficacy and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dupilumab, the first biological drug to be approved for the treatment of moderate to severe atopic dermatitis in adolescents and adults, has shown good efficacy and safety in clinical trials.
OBJECTIVE
To evaluate real-world data on the efficacy and safety of dupilumab in atopic dermatitis.
METHODS
PubMed and EMBASE were searched for observational studies with data on efficacy, drug survival, and safety of dupilumab for the treatment of atopic dermatitis. Primary outcomes were mean percentage change in Eczema Area and Severity Index (EASI) score and proportion of atopic dermatitis patients achieving 50%, 75%, and 90% improvement in EASI score after dupilumab therapy.
RESULTS
Twenty-two unique studies encompassing 3303 atopic dermatitis patients were included. After 16 weeks of dupilumab therapy, the pooled proportion of patients achieving 50%, 75%, and 90% EASI score improvement was 85.1%, 59.8%, and 26.8%, respectively, and the weighted mean reduction in EASI score was 69.6%. Conjunctivitis was the most common adverse event, reported in a pooled proportion of 26.1%.
LIMITATIONS
Limited data in terms of size and follow-up time were available.
CONCLUSION
Real-world data show that dupilumab is a successful and well-tolerated therapy for atopic dermatitis, but ocular adverse events commonly occur. Registries are needed to monitor for adverse events.
Topics: Antibodies, Monoclonal, Humanized; Blepharitis; Conjunctivitis; Dermatitis, Atopic; Dermatologic Agents; Herpes Simplex; Humans; Interleukin-4 Receptor alpha Subunit; Keratitis; Treatment Outcome
PubMed: 32822798
DOI: 10.1016/j.jaad.2020.08.051 -
The British Journal of Dermatology Feb 2022Previous studies have found conflicting results about the association of atopic dermatitis (AD) with hypertension. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previous studies have found conflicting results about the association of atopic dermatitis (AD) with hypertension.
OBJECTIVES
To determine whether AD and AD severity are associated with hypertension.
METHODS
A systematic review was performed of published studies in Ovid MEDLINE, Embase, Scopus, Web of Science, and GREAT (Global Resource for EczemA Trials) databases. At least two reviewers conducted title/abstract, full-text review and data extraction. Quality of evidence was assessed using the Newcastle-Ottawa Scale.
RESULTS
Fifty-one studies met the inclusion criteria and 19 had sufficient data for meta-analysis. AD was associated with higher odds of hypertension compared with healthy controls [increased in nine of 16 studies; pooled prevalence 16·4% vs. 13·8%; random-effects regression, pooled unadjusted odds ratio (OR) 1·16, 95% confidence interval (CI) 1·04-1·30], but lower odds of hypertension compared with psoriasis [decreased in five of eight studies; 15·4% vs. 24·8% (OR 0·53, 95% CI 0·37-0·76)]. In particular, moderate-to-severe AD was associated with hypertension compared with healthy controls [increased in four of six studies; 24·9% vs. 14·7% (OR 2·33, 95% CI 1·10-4·94)]. Hypertension was commonly reported as an adverse event secondary to AD treatments, particularly systemic ciclosporin A. Limitations include lack of longitudinal studies or individual-level data, and potential confounding.
CONCLUSIONS
AD, particularly moderate-to-severe disease, was associated with increased hypertension compared with healthy controls, but with lower odds than for psoriasis.
Topics: Dermatitis, Atopic; Eczema; Humans; Hypertension; Medical History Taking; Prevalence
PubMed: 34319589
DOI: 10.1111/bjd.20661 -
Veterinary Dermatology Feb 2021Feline allergic skin disease and asthma occur regularly in small animal practice. (Review)
Review
BACKGROUND
Feline allergic skin disease and asthma occur regularly in small animal practice.
OBJECTIVES
To provide evidence-based recommendations for small animal practitioners on the treatment of feline atopic syndrome (FAS).
METHODS AND MATERIALS
The authors reviewed the literature available before February 2020, prepared a detailed evidence-based literature review and made recommendations based on the evaluated evidence.
RESULTS
Sixty-six papers and abstracts were identified describing treatment interventions for FAS and evaluated to establish treatment recommendations. For many treatment options, the papers were retrospective, open studies or case reports.
CONCLUSION AND CLINICAL RELEVANCE
In this review, there was good evidence for the efficacy of systemic glucocorticoids and ciclosporin, and limited evidence for the efficacy of topical glucocorticoids, oclacitinib and allergen-specific immunotherapy in feline atopic skin syndrome. Evidence pointed to low-to-moderate efficacy for antihistamines, fatty acids and palmitoyl ethanolamide. In feline asthma, there was good evidence for the efficacy of oral and inhaled glucocorticoids, and limited evidence of moderate efficacy for allergen-specific immunotherapy. Evidence supported low-to-moderate efficacy of mesenchymal stem cells, inhaled lidocaine and oclacitinib as treatments for feline asthma. For almost all therapeutic options (with the exception of glucocorticoids and ciclosporin), more randomised controlled trials are needed.
Topics: Allergens; Animals; Cat Diseases; Cats; Cyclosporine; Dermatitis, Atopic; Desensitization, Immunologic; Glucocorticoids; Immunotherapy; Retrospective Studies; Syndrome
PubMed: 33470011
DOI: 10.1111/vde.12933 -
JAAD International Mar 2021Complementary and alternative medicine (CAM) treatments are growing in popularity as alternative treatments for common skin conditions. (Review)
Review
BACKGROUND
Complementary and alternative medicine (CAM) treatments are growing in popularity as alternative treatments for common skin conditions.
OBJECTIVES
To perform a systematic review and meta-analysis to determine the tolerability and treatment response to CAM treatments in acne, atopic dermatitis (AD), and psoriasis.
METHODS
PubMed/Medline and Embase databases were searched to identify eligible studies measuring the effects of CAM in acne, AD, and psoriasis. Effect size with 95% confidence interval (CI) was estimated using the random-effect model.
RESULTS
The search yielded 417 articles; 40 studies met the inclusion criteria. The quantitative results of CAM treatment showed a standard mean difference (SMD) of 3.78 (95% CI [-0.01, 7.57]) and 0.58 (95% CI [-6.99, 8.15]) in the acne total lesion count, a SMD of -0.70 (95% CI [-1.19, -0.21]) in the eczema area and severity index score and a SMD of 0.94 (95% CI [-0.83, 2.71]) in the scoring of atopic dermatitis score for AD, and a SMD of 3.04 (95% CI [-0.35, 6.43]) and 5.16 (95% CI [-0.52, 10.85]) in the Psoriasis Area Severity Index score for psoriasis.
LIMITATIONS
Differences between the study designs, sample sizes, outcome measures, and treatment durations limit the generalizability of data.
CONCLUSIONS
Based on our quantitative findings we conclude that there is insufficient evidence to support the efficacy and the recommendation of CAM for acne, AD, and psoriasis.
PubMed: 34409356
DOI: 10.1016/j.jdin.2020.11.001 -
Dermatology (Basel, Switzerland) 2018Atopic dermatitis (AD) may be associated with the metabolic syndrome and by that carry an increased risk of cardio-vascular disease. Our objective was to provide an... (Review)
Review
Atopic dermatitis (AD) may be associated with the metabolic syndrome and by that carry an increased risk of cardio-vascular disease. Our objective was to provide an update on current knowledge of the association between AD and metabolic syndrome, including each component of the metabolic syndrome. A systematic literature review was performed to identify studies investigating the association between metabolic syndrome and AD from PubMed, Embase, and the Cochrane Library in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A total of 14 studies, investigating the association between AD and the metabolic syndrome or AD and components of metabolic syndrome fulfilled the inclusion criteria and were included. It seems unlikely that the association between AD and metabolic syndrome is causal. However, women with AD tended to have components of metabolic syndrome more often than women without AD. There was a positive association between AD and central obesity measured as waist circumference, and this association was stronger for women than men. Despite conflicting results regarding hypertension, the association between hypertension and AD also appeared stronger for women. On the other hand, the association between AD and hyperglycemia appears unlikely, and the association between AD and cholesterol levels was inconsistent. In conclusion, it remains unclear whether AD is a risk factor for metabolic syndrome and its components. However, data indicate that central obesity is associated with AD and that the association is stronger for women than men.
Topics: Dermatitis, Atopic; Humans; Metabolic Syndrome
PubMed: 30110673
DOI: 10.1159/000491593 -
Genes Apr 2020Atopic dermatitis is a common inflammatory skin disorder that affects up to 15-20% of the population and is characterized by recurrent eczematous lesions with intense...
BACKGROUND
Atopic dermatitis is a common inflammatory skin disorder that affects up to 15-20% of the population and is characterized by recurrent eczematous lesions with intense itching. As a heterogeneous disease, multiple factors have been suggested to explain the nature of atopic dermatitis (AD), and its high prevalence makes it necessary to periodically compile and update the new information available. In this systematic review, the focus is set at the genetic and epigenetic studies carried out in the last years.
METHODS
A systematic literature review was conducted in three scientific publication databases (PubMed, Cochrane Library, and Scopus). The search was restricted to publications indexed from July 2016 to December 2019, and keywords related to atopic dermatitis genetics and epigenetics were used.
RESULTS
A total of 73 original papers met the inclusion criteria established, including 9 epigenetic studies. A total of 62 genes and 5 intergenic regions were described as associated with AD.
CONCLUSION
() polymorphisms are confirmed as key genetic determinants for AD development, but also epigenetic regulation and other genes with functions mainly related to the immune system and extracellular matrix, reinforcing the notion of skin homeostasis breakage in AD.
Topics: Dermatitis, Atopic; Epigenesis, Genetic; Filaggrin Proteins; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; S100 Proteins; Skin
PubMed: 32325630
DOI: 10.3390/genes11040442 -
Nutrition (Burbank, Los Angeles County,... Sep 2016Despite the evidence supporting the use of vitamin D supplements for managing atopic dermatitis (AD), no meta-analysis providing definite conclusions in this field has... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Despite the evidence supporting the use of vitamin D supplements for managing atopic dermatitis (AD), no meta-analysis providing definite conclusions in this field has been reported. The purpose of the present study was to conduct a systematic review and meta-analysis of all controlled studies of vitamin D for treating AD to elucidate the efficacy of vitamin D for alleviating the symptoms of AD.
METHODS
Literature searches were conducted using Ovid-MEDLINE, EMBASE, Web of Science, Cochrane Library, and Korean and Chinese databases. Search terms used were "vitamin D", "atopic dermatitis", "randomized", "controlled trial", and "clinical trial". Random effects models were used to calculate the mean difference, with 95% confidence intervals to analyze the effects of vitamin D supplementation for severity of AD.
RESULTS
Initial searches yielded 266 citations. Of these original results, nine met specific selection criteria. Four of the randomized controlled trials compared the efficacy of vitamin D with a placebo on severity of AD and were included in the meta-analysis. The vitamin D supplementation interventions showed a higher mean difference in severity of AD symptoms (mean difference = -5.81, 95% CI: -9.03 to -2.59, P = 0.0004, I(2) = 50%).
CONCLUSIONS
Vitamin D has a potentially significant role for improving the symptoms of AD. The results from this study suggest that vitamin D supplementation may help ameliorate the severity of AD, and can be considered as a safe and tolerable therapy. However, larger-scale studies over a longer duration of treatment are needed to confirm this conclusion.
Topics: Dermatitis, Atopic; Dietary Supplements; Humans; Vitamin D; Vitamins
PubMed: 27061361
DOI: 10.1016/j.nut.2016.01.023