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Dermatology and Therapy Nov 2023Assessing treatment response is key to determining treatment value in atopic dermatitis (AD). Currently, response is assessed using various clinician- or... (Review)
Review
INTRODUCTION
Assessing treatment response is key to determining treatment value in atopic dermatitis (AD). Currently, response is assessed using various clinician- or patient-reported measures and response criteria. This variation creates a mismatch of evidence across trials, hindering the ability of clinicians, regulators, and payers to compare the efficacy of treatments. This review identifies which measures and criteria are used to determine response in clinical trials and health technology assessments (HTAs). Moreover, it systematically reviews the psychometric performance of those measures and criteria to understand which perform best in capturing patient-relevant symptoms and treatment benefits.
METHODS
A scoping review of clinical trials and HTAs in AD identified the following measures for inclusion: the Eczema Area and Severity Index (EASI), the Investigator's Global Assessment (IGA), the Dermatology Life Quality Index (DLQI) and the Peak Pruritus Numerical Rating Scale (PP-NRS). A systematic search was performed in MEDLINE and Embase to identify studies testing the psychometric performance of these measures in adults or adolescents with AD.
RESULTS
A lack of consistency in the assessment of response was observed across clinical trials and HTAs. Important gaps in psychometric evidence were identified. No content validations of the EASI and IGA in AD were found, while some quantitative studies suggested that these measures fail to capture itch, a core symptom. The PP-NRS and DLQI performed well. No studies compared the performance of different response criteria.
CONCLUSION
Content validation of the PP-NRS confirmed the importance of itch as a core symptom and treatment priority in AD; however, itch is not well covered in the EASI or IGA. Including the PP-NRS in clinical trials and HTAs will better capture patient-relevant benefit and response. Although various response criteria were used, no studies compared the performance of different criteria to inform which were most appropriate to compare treatments in clinical trials and HTAs.
PubMed: 37747670
DOI: 10.1007/s13555-023-01038-3 -
The Journal of Allergy and Clinical... Dec 2023Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes.
OBJECTIVE
We sought to systematically synthesize the benefits and harms of AD systemic treatments.
METHODS
For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna).
RESULTS
The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain.
CONCLUSIONS
Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.
Topics: Humans; Dermatitis, Atopic; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Eczema; Asthma; Treatment Outcome
PubMed: 37678577
DOI: 10.1016/j.jaci.2023.08.029 -
The Journal of Allergy and Clinical... Dec 2023Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects.
OBJECTIVE
We sought to systematically synthesize the benefits and harms of AD prescription topical treatments.
METHODS
For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT databases to September 5, 2022, for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using 7 groups-group 1 being most potent. This review is registered in the Open Science Framework (https://osf.io/q5m6s).
RESULTS
The 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty evidence, pimecrolimus improved 6 of 7 outcomes-among the best for 2; high-dose tacrolimus (0.1%) improved 5-among the best for 2; low-dose tacrolimus (0.03%) improved 5-among the best for 1. With moderate- to high-certainty evidence, group 5 TCS improved 6-among the best for 3; group 4 TCS and delgocitinib improved 4-among the best for 2; ruxolitinib improved 4-among the best for 1; group 1 TCS improved 3-among the best for 2. These interventions did not increase harm. Crisaborole and difamilast were intermediately effective, but with uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus.
CONCLUSIONS
For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective.
Topics: Humans; Dermatitis, Atopic; Tacrolimus; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Dermatologic Agents; Asthma; Eczema; Anti-Bacterial Agents
PubMed: 37678572
DOI: 10.1016/j.jaci.2023.08.030 -
JAAD International Dec 2023
PubMed: 37663167
DOI: 10.1016/j.jdin.2023.05.014 -
Antioxidants (Basel, Switzerland) Jul 2023Skin conditions are a significant cause of fatal and nonfatal disease burdens globally, ranging from mild irritations to debilitating diseases. Oxidative stress, which... (Review)
Review
Skin conditions are a significant cause of fatal and nonfatal disease burdens globally, ranging from mild irritations to debilitating diseases. Oxidative stress, which is an imbalance between reactive oxygen species and the cells' ability to repair damage, is implicated in various skin diseases. Antioxidants have been studied for their potential benefits in dermatologic health, but the evidence is limited and conflicting. Herein, we conducted a systematic review of controlled trials, meta-analyses, and Cochrane review articles to evaluate the current evidence on the utility of antioxidant supplementation for adjunct prevention and treatment of skin disease and to provide a comprehensive assessment of their role in promoting dermatologic health. The Cochrane Library, PubMed, EMBASE, and Epistemonikos databases were queried. Eligibility criteria included (1) primary focus on nanoparticle utility for skin cancer; (2) includes measurable outcomes data with robust comparators; (3) includes a number of human subjects or cell-line types, where applicable; (4) English language; and (5) archived as full-text journal articles. A total of 55 articles met the eligibility criteria for the present review. Qualitative analysis revealed that topical and oral antioxidant supplementation has demonstrated preliminary efficacy in reducing sunburns, depigmentation, and photoaging. Dietary exogenous antioxidants (namely vitamins A, C, and E) have shown chemopreventive effects against skin cancer. Antioxidant supplementation has also shown efficacy in treating non-cancer dermatoses, including rosacea, psoriasis, atopic dermatitis, and acne vulgaris. While further studies are needed to validate these findings on a larger scale, antioxidant supplementation holds promise for improving skin health and preventing skin diseases.
PubMed: 37627498
DOI: 10.3390/antiox12081503 -
Asian Pacific Journal of Allergy and... Aug 2023The effect of probiotics in the treatment of atopic dermatitis (AD) is inconclusive, partially due to the heterogeneities of AD.
BACKGROUND
The effect of probiotics in the treatment of atopic dermatitis (AD) is inconclusive, partially due to the heterogeneities of AD.
OBJECTIVE
The aim of the present study was to investigate the efficacy of probiotics in the treatment of AD with a subgroup analysis according to country, severity of AD, duration of supplementation, and probiotic strain.
METHODS
Original articles reporting the therapeutic efficacy of probiotics for AD were identified by searching PubMed, Cochrane Library databases, and Embase from inception to September 30, 2022.
RESULTS
This meta-analysis included 1,382 patients with AD from 25 randomized controlled trials. Probiotic supplementation was effective for the treatment of AD, reflected in a significant decrease in the SCORing Atopic Dermatitis (SCORAD) index (SMD, -4.0; 95%CI, -7.3 to -0.7). The subgroup analysis showed a significant therapeutic effect for AD among patients with mild or moderate AD (SMD, -1.4; 95%CIs -2.2 to -0.7), in those supplemented for more than three months (SMD, -5.1; 95%CIs -9.7 to -0.4), and in those supplemented with a probiotic that contained Lactobacillus spp. strains combined with or without other strains (SMD, -4.4; 95%CIs -8.0 to -0.8). In addition, the therapeutic effects of probiotics showed differences according to country and geographic region.
CONCLUSIONS
Probiotics can be beneficial for the treatment of AD, and their therapeutic effect may be individually tailored to improve it based on the severity of AD, strain of probiotics, duration of supplementation, and geographic region.
PubMed: 37578483
DOI: 10.12932/AP-280323-1576 -
Healthcare (Basel, Switzerland) Jul 2023Understanding the contributions of community pharmacists as first-line health providers is important to the management of atopic dermatitis, though little is known about... (Review)
Review
Understanding the contributions of community pharmacists as first-line health providers is important to the management of atopic dermatitis, though little is known about their contribution. A systematic review was carried out to examine practices and perceptions of the role of community pharmacists. A literature search was conducted in five different databases. Full-text primary research studies, which involved practices and perceptions of the role of community pharmacists in the management of atopic dermatitis, previously published in peer reviewed journals were used. Critical appraisal of included studies was performed using the Mixed Methods Appraisal Tool. Data were extracted and thematically synthesized to generate descriptive and analytical themes. The confidence of the findings of the included studies was assessed via either GRADE or CERQual. Twenty-three studies were included. Findings showed that community pharmacists lacked knowledge of the uses of topical corticosteroids. The recommendations of other treatments were limited. Pharmacists generally undertook dermatology training after graduation. Analytical themes indicated that the practices of community pharmacists were poor and misled patients. Inappropriate education in initial training was identified as a potential reason for their poor practices. This systematic review reveals a gap between patients' needs in practice and dermatological education provided to community pharmacists. Novel approaches regarding education and training should be explored to improve pharmacists' dermatological knowledge and skills.
PubMed: 37570399
DOI: 10.3390/healthcare11152159 -
Medicine Aug 2023To assess the efficacy and safety of Tralokinumab in the treatment of moderate-to-severe atopic dermatitis (AD). (Meta-Analysis)
Meta-Analysis
BACKGROUND
To assess the efficacy and safety of Tralokinumab in the treatment of moderate-to-severe atopic dermatitis (AD).
METHODS
PubMed, Embase, Clinical Trials Website, and Cochrane Library were systematically searched for eligible randomized controlled trials which assessed the effects of Tralokinumab on AD. Primary outcomes included Scoring Atopic Dermatitis score, EASI-75%, and Investigator's Global Assessment score of 0 or 1 in 12 to 16 weeks. Secondary outcomes included the Eczema area and severity index score, the Numeric Rating Scales score, the dermatology life quality index score, and the overall incidence of adverse events. The quality of included studies was evaluated using the Cochrane System and the modified Jadad scale. Analysis was performed using Stata 16 software.
RESULTS
Eight randomized controlled trials involving 2878 patients were included in this meta-analysis. Compared to placebo, Tralokinumab treatment exhibited a significantly higher Scoring Atopic Dermatitis score [SMD = -0.53, 95% confidence intervals [CI]: -0.62 to -0.44, P < .00001], an increased number of patients with EASI-75% [odds ratio (OR) = 2.44, 95% CI: 2.00-2.97, P < .00001] and Investigator's Global Assessment score of 0 or 1 in 12 to 16 weeks [OR = 2.12, 95% CI: 1.71-2.63, P < .00001]. No significant difference was observed in the incidence of overall adverse events [OR = 1.00, 95% CI: 0.85-1.18, P = 1.00] between the 2 groups.
CONCLUSION
Tralokinumab is effective and safe in treatment of moderate-to-severe AD.
Topics: Humans; Dermatitis, Atopic; Treatment Outcome; Randomized Controlled Trials as Topic; Antibodies, Monoclonal; Severity of Illness Index; Double-Blind Method
PubMed: 37543792
DOI: 10.1097/MD.0000000000034516 -
Clinical and Experimental Medicine Dec 2023Thymic stromal lymphopoietin (TSLP) is critical in developing allergic responses, including atopic dermatitis (AD). We systematically reviewed the literature to complete... (Meta-Analysis)
Meta-Analysis Review
Thymic stromal lymphopoietin (TSLP) is critical in developing allergic responses, including atopic dermatitis (AD). We systematically reviewed the literature to complete a meta-analysis to quantitatively summarize the levels of serum TSLP in AD. The study was prospectively registered in the PROSPERO database (ID = CRD42021242628). The PUBMED, SCOPUS, and Cochrane Library databases were reviewed, and original articles investigating serum TSLP in AD patients were included. Differences in TSLP levels of AD patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed by applying the Newcastle‒Ottawa Scale. Fourteen studies, which included 1,032 AD patients and 416 controls, were included. Meta-analysis showed that TSLP levels were significantly higher in the AD group than in the control group (SMD = 2.21, 95% CI 1.37-3.06, p < 0.001). Stratification by geographical region, age, disease severity, TSLP determination method, sample size, and study quality revealed significantly elevated TSLP levels in European AD patients (SMD = 3.48, 95% CI 1.75-5.21, p < 0.0001), adult AD patients (SMD = 4.10, 95% CI 2.00-6.21, p < 0.0001), child AD patients (SMD = 0.83, 95% CI 0.08-1.59, p = 0.031), and all severity groups with AD compared with the control group (mild: SMD = 1.15, 95% CI 0.14-2.16, p = 0.025; moderate: SMD = 2.48, 95% CI 0.33-4.62, p = 0.024; and severe: SMD = 8.28, 95% CI 4.82-11.74, p = 2.72e-6). Noticeably, adults showed higher serum TSLP levels than children with AD, and serum TSL levels increased according to AD severity. In conclusion, our meta-analysis demonstrates that circulating TSLP levels are elevated in patients with AD. Future studies are warranted to further elucidate the sources of heterogeneity.
Topics: Adult; Child; Humans; Cytokines; Dermatitis, Atopic; Thymic Stromal Lymphopoietin
PubMed: 37515689
DOI: 10.1007/s10238-023-01147-5 -
Genes Jul 2023Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we... (Meta-Analysis)
Meta-Analysis
Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we comprehensively evaluated the available literature to determine the association of candidate genes in AD to gain additional insight into the etiopathogenesis of the disease. We systematically screened all studies that explored the association between polymorphisms and AD risks in cases of European and Asian ancestry and synthesized the available evidence through a random-effects meta-analysis. We identified 99 studies that met our inclusion/exclusion criteria that examined 17 candidate loci in Europeans and 14 candidate genes in Asians. We confirmed the significant associations between variants in both European and Asian populations and AD risk, while synthesis of the available data revealed novel loci mapped to and genes in Europeans and and in Asians that have not yet been identified by genome-wide association studies. Our findings provide comprehensive evidence for AD risk loci in cases of both European and Asian ancestries, validating previous associations as well as revealing novel loci that could imply previously unexplored biological pathways.
Topics: Humans; Dermatitis, Atopic; Genetic Predisposition to Disease; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Asian People; European People
PubMed: 37510360
DOI: 10.3390/genes14071456