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JAMA Dermatology May 2022Systemic treatments for atopic dermatitis are being evaluated primarily in placebo-controlled trials; network meta-analysis can provide relative efficacy and safety... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Systemic treatments for atopic dermatitis are being evaluated primarily in placebo-controlled trials; network meta-analysis can provide relative efficacy and safety estimates for treatments that have not been compared head to head.
OBJECTIVE
To compare reported measures of efficacy and assessments of safety in clinical trials of systemic treatments for atopic dermatitis in a living systematic review and network meta-analysis.
DATA SOURCES
The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, Global Resource of EczemA Trials database, and trial registries were searched through June 15, 2021.
STUDY SELECTION
Randomized clinical trials examining 8 or more weeks of treatment with systemic immunomodulatory medications for moderate-to-severe atopic dermatitis were included after screening titles, abstracts, and papers in duplicate.
DATA EXTRACTION AND SYNTHESIS
Data were abstracted in duplicate. Bayesian network meta-analyses and assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed. The updated analysis was completed from June to December 2021.
MAIN OUTCOMES AND MEASURES
Outcomes include change in Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), and Peak Pruritus Numeric Rating Scales (PP-NRS).
RESULTS
Since October 2019, 21 new studies were added, for a total of 60 trials with 16 579 patients. Up to 16 weeks of treatment in adults, abrocitinib, 200 mg daily (mean difference [MD], 2.2; 95% credible interval [CrI], 0.2-4.0; high certainty) and upadacitinib, 30 mg daily (MD, 2.7; 95% CrI, 0.6-4.7; high certainty) were associated with reduced EASI slightly more than dupilumab, 600 mg then 300 mg every 2 weeks. Abrocitinib, 100 mg daily (MD, -2.1; 95% CrI, -4.1 to -0.3; high certainty), baricitinib, 4 mg daily (MD, -3.2; 95% CrI, -5.7 to -0.8; high certainty), baricitinib, 2 mg daily (MD, -5.2; 95% CrI, -7.5 to -2.9; high certainty) and tralokinumab, 600 mg then 300 mg every 2 weeks (MD, -3.5; 95% CrI, -5.8 to -1.3; high certainty) were associated with reduced EASI slightly less than dupilumab. There was little or no difference between upadacitinib, 15 mg daily, and dupilumab (MD, 0.2; 95% CrI, -1.9 to 2.2; high certainty). The pattern of results was similar for POEM, DLQI, and PP-NRS.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, abrocitinib, 200 mg; and upadacitinib, 30 mg daily, were associated with slightly better scores than dupilumab, and upadacitinib, 15 mg daily, was associated with similar scores to dupilumab. Abrocitinib, 100 mg daily, baricitinib, 4 mg and 2 mg daily, and tralokinumab, 300 mg, every 2 weeks were associated with slightly worse scores.
Topics: Adult; Bayes Theorem; Dermatitis, Atopic; Eczema; Humans; Network Meta-Analysis; Pruritus; Severity of Illness Index; Treatment Outcome
PubMed: 35293977
DOI: 10.1001/jamadermatol.2022.0455 -
Acta Dermato-venereologica Aug 2020Bullous pemphigoid is an autoimmune subepithelial disease characterised by pruritus followed by urticarial plaques and finally bullae on the skin and mucosa....
Bullous pemphigoid is an autoimmune subepithelial disease characterised by pruritus followed by urticarial plaques and finally bullae on the skin and mucosa. Drug-associated bullous pemphigoid (DABP) is a term used to describe instances of bullous pemphigoid demonstrating clinical, histological, or immunopathological features identical or similar to those of the idiopathic form of bullous pemphigoid, associated with the systemic ingestion, or topical application of particular drugs. In this study, we conducted a comprehensive search of the literature according to PRISMA guidelines and a total of 170 publications were included in the final qualitative analysis. In conclusion, 89 drugs were implicated in DABP. The strongest evidence for DABP is seen with gliptins, PD-1/PD-L1 inhibitors, loop diuretics, penicillin and derivatives. An appreciation of the medications associated with bullous pemphigoid enables clinicians to identify potential cases of DABP earlier and cease the offending medication.
Topics: Blister; Humans; Pemphigoid, Bullous; Pharmaceutical Preparations; Pruritus; Skin
PubMed: 32176310
DOI: 10.2340/00015555-3457 -
Journal of Alternative and... Oct 2020The aim of this systematic review with meta-analysis was to describe the status on the effects of physical scar treatments on pain, pigmentation, pliability, pruritus,... (Meta-Analysis)
Meta-Analysis
The aim of this systematic review with meta-analysis was to describe the status on the effects of physical scar treatments on pain, pigmentation, pliability, pruritus, scar thickening, and surface area. Systematic review and meta-analysis. Adults with any kind of scar tissue. Physical scar management versus control or no scar management. Pain, pigmentation, pliability, pruritus, surface area, scar thickness. The overall results revealed that physical scar management is beneficial compared with the control treatment regarding the management of pain ( = 0.012), pruritus ( < 0.001), pigmentation ( = 0.010), pliability ( < 0.001), surface area ( < 0.001), and thickness ( = 0.022) of scar tissue in adults. The observed risk of bias was high for blinding of participants and personnel (47%) and low for other bias (100%). Physical scar management demonstrates moderate-to-strong effects on improvement of scar issues as related to signs and symptoms. These results show the importance of specific physical management of scar tissue.
Topics: Cicatrix; Female; Humans; Male; Pigmentation Disorders; Postoperative Complications; Pruritus; Wound Healing
PubMed: 32589450
DOI: 10.1089/acm.2020.0109 -
Biomolecules Mar 2023Dupilumab was first approved for the treatment of atopic dermatitis (AD) and blocks the signaling of interleukin (IL)-4 and -13. Several other chronic skin conditions... (Review)
Review
Dupilumab was first approved for the treatment of atopic dermatitis (AD) and blocks the signaling of interleukin (IL)-4 and -13. Several other chronic skin conditions share mechanistic overlaps with AD in their pathophysiology, i.e., are linked to type 2 inflammation. Most recently, dupilumab was approved by the U.S. Food and Drug Administration for prurigo nodularis (PN). Given its relatively good safety profile, effective off-label use of dupilumab has been reported for a multitude of dermatologic diseases and several clinical trials for dermatologic skin conditions are currently ongoing. We conducted a systematic review of applications of dupilumab in dermatology other than AD and PN by searching the databases PubMed/Medline, Scopus, Web of Science and Cochrane Library as well as the clinical trial registry ClinicalTrials.gov. We found several reports for effective treatment of bullous autoimmune diseases, eczema, prurigo, alopecia areata, chronic spontaneous urticaria, Netherton syndrome and a variety of other chronic inflammatory skin diseases.
Topics: Humans; Prurigo; Antibodies, Monoclonal, Humanized; Dermatitis, Atopic; Skin
PubMed: 37189381
DOI: 10.3390/biom13040634 -
Phytotherapy Research : PTR Aug 2016Turmeric (Curcuma longa), a commonly used spice throughout the world, has been shown to exhibit antiinflammatory, antimicrobial, antioxidant, and anti-neoplastic... (Review)
Review
Turmeric (Curcuma longa), a commonly used spice throughout the world, has been shown to exhibit antiinflammatory, antimicrobial, antioxidant, and anti-neoplastic properties. Growing evidence shows that an active component of turmeric, curcumin, may be used medically to treat a variety of dermatologic diseases. This systematic review was conducted to examine the evidence for the use of both topical and ingested turmeric/curcumin to modulate skin health and function. The PubMed and Embase databases were systematically searched for clinical studies involving humans that examined the relationship between products containing turmeric, curcumin, and skin health. A total of 234 articles were uncovered, and a total of 18 studies met inclusion criteria. Nine studies evaluated the effects of ingestion, eight studies evaluated the effects of topical, and one study evaluated the effects of both ingested and topical application of turmeric/curcumin. Skin conditions examined include acne, alopecia, atopic dermatitis, facial photoaging, oral lichen planus, pruritus, psoriasis, radiodermatitis, and vitiligo. Ten studies noted statistically significant improvement in skin disease severity in the turmeric/curcumin treatment groups compared with control groups. Overall, there is early evidence that turmeric/curcumin products and supplements, both oral and topical, may provide therapeutic benefits for skin health. However, currently published studies are limited and further studies will be essential to better evaluate efficacy and the mechanisms involved. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: Anti-Inflammatory Agents; Curcuma; Humans; Skin
PubMed: 27213821
DOI: 10.1002/ptr.5640 -
ESMO Open Apr 2023Programmed death-ligand 1[PD-(L)1], cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) inhibitors are recent breakthroughs in... (Review)
Review
Programmed death-ligand 1[PD-(L)1], cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) inhibitors are recent breakthroughs in cancer treatment, however not all patients benefit from it. Thus new therapies are under investigation, such as anti-TIGIT [anti-T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domains] antibodies. TIGIT is an immune checkpoint inhibiting lymphocyte T cells by several mechanisms. In vitro models showed its inhibition could restore antitumor response. Furthermore, its association with anti-PD-(L)1 therapies could synergistically improve survival. We carried out a review of the clinical trial about TIGIT referenced in the PubMed database, finding three published clinical trials on anti-TIGIT therapies. Vibostolimab was evaluated in a phase I alone or in combination with pembrolizumab. The combination had an objective response rate of 26% in patients with a non-small-cell lung cancer (NSCLC) naïve of anti-programmed cell death protein 1 (anti-PD-1). Etigilimab was tested in a phase I alone or in combination with nivolumab, but the study was stopped due to business reasons. In the phase II CITYSCAPE trial, tiragolumab demonstrated higher objective response rate and progression-free survival in combination with atezolizumab than atezolizumab alone in advanced PD-L1-high NSCLC. The ClinicalTrials.gov database references 70 trials of anti-TIGIT in patients with cancer, 47 of them with ongoing recruitment. Only seven were phase III, including five about patients with NSCLC, mostly with combination therapy. Data from phase I-II trials highlighted that targeting TIGIT represents a safe therapeutic approach, with an acceptable toxicity profile maintained when adding anti-PD-(L)1 antibodies. Frequent adverse events were pruritus, rash, and fatigue. Grade 3-4 adverse events were reported in nearly one in three patients. Anti-TIGIT antibodies are under development as a novel immunotherapy approach. A promising research area includes the combination with anti-PD-1 therapies in advanced NSCLCs.
Topics: Humans; Antibodies, Monoclonal; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Nivolumab
PubMed: 36933320
DOI: 10.1016/j.esmoop.2023.101184 -
American Journal of Kidney Diseases :... Nov 2017Uremic pruritus is a common and burdensome symptom afflicting patients with advanced chronic kidney disease (CKD) and has been declared a priority for CKD research by... (Review)
Review
BACKGROUND
Uremic pruritus is a common and burdensome symptom afflicting patients with advanced chronic kidney disease (CKD) and has been declared a priority for CKD research by patients. The optimal treatments for uremic pruritus are not well defined.
STUDY DESIGN
Systematic review.
SETTING & POPULATION
Adult patients with advanced CKD (stage ≥ 3) or receiving any form of dialysis.
SELECTION CRITERIA FOR STUDIES
PubMed, CINAHL, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and ClinicalTrials.gov from their inception to March 6, 2017, were systematically searched for randomized controlled trials (RCTs) of uremic pruritus treatments in patients with advanced CKD (stage ≥ 3) or receiving any form of dialysis. 2 reviewers extracted data independently. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool.
INTERVENTION
Any intervention for the treatment of uremic pruritus was included.
OUTCOMES
A quantitative change in pruritus intensity on a visual analogue, verbal rating, or numerical rating scale.
RESULTS
44 RCTs examining 39 different treatments were included in the review. These treatments included gabapentin, pregabalin, mast cell stabilizers, phototherapy, hemodialysis modifications, and multiple other systemic and topical treatments. The largest body of evidence was found for the effectiveness of gabapentin. Due to the limited number of trials for the other treatments included, we are unable to comment on their efficacy. Risk of bias in most studies was high.
LIMITATIONS
Heterogeneity in design, treatments, and outcome measures rendered comparisons difficult and precluded meta-analysis.
CONCLUSIONS
Despite the acknowledged importance of uremic pruritus to patients, with the exception of gabapentin, the current evidence for treatments is weak. Large, simple, rigorous, multiarm RCTs of promising therapies are urgently needed.
Topics: Administration, Cutaneous; Amines; Analgesics; Anti-Asthmatic Agents; Antipruritics; Capsaicin; Cromolyn Sodium; Cyclohexanecarboxylic Acids; Gabapentin; Humans; Kidney Failure, Chronic; Phototherapy; Pregabalin; Pruritus; Renal Dialysis; Renal Insufficiency, Chronic; Uremia; gamma-Aminobutyric Acid
PubMed: 28720208
DOI: 10.1053/j.ajkd.2017.05.018 -
The Journal of Allergy and Clinical... Jan 2023Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear.
OBJECTIVE
We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD.
METHODS
As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence.
RESULTS
Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings.
CONCLUSIONS
SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.
Topics: Adult; Animals; Humans; Child; Dermatitis, Atopic; Quality of Life; Bayes Theorem; Desensitization, Immunologic; Pyroglyphidae; Hypersensitivity; Asthma; Allergens; Sublingual Immunotherapy; Dermatophagoides pteronyssinus; Eczema
PubMed: 36191689
DOI: 10.1016/j.jaci.2022.09.020 -
International Journal of Nursing Studies Mar 2020In aged nursing care receivers, the prevalence of adverse skin conditions such as xerosis cutis, intertrigo, pressure ulcers or skin tears is high. Adequate skin care...
BACKGROUND
In aged nursing care receivers, the prevalence of adverse skin conditions such as xerosis cutis, intertrigo, pressure ulcers or skin tears is high. Adequate skin care strategies are an effective method for maintaining and enhancing skin health and integrity in this population.
OBJECTIVES
The objective was to summarize the empirical evidence about the effects and effectiveness of non-drug topical skin care interventions to promote and to maintain skin integrity and skin barrier function in the aged, to identify outcome domains and outcome measurement instruments in this field.
DESIGN
An update of a previous systematic review published in 2013 was conducted.
DATA SOURCES
Databases MEDLINE and EMBASE via OvidSP and CINAHL (original search January 1990 to August 2012, update September 2012 to May 2018) and reference lists were searched. Forward searches in Web of Science were conducted.
METHODS
A review protocol was registered in Prospero (CRD42018100792). Main inclusion criteria were primary intervention studies reporting treatment effects of basic skin care strategies in aged people with a lower limit of age range of 50 years and published between 1990 and 2018. Primary empirical studies were included with experimental study designs including randomized controlled trials and quasi-experimental designs. Methodological quality of included randomized controlled trials was evaluated using the Cochrane Collaboration's Tool for assessing risk of bias. Levels of evidence were assigned to all included studies.
RESULTS
Sixty-three articles were included in the final analysis reporting effects of interventions to treat and/or to prevent skin dryness, pruritus, general skin barrier improvement, incontinence-associated dermatitis, skin tears and pressure ulcers. Skin cleansers containing syndets or amphotheric surfactants compared with standard soap and water improved skin dryness. Lipophilic leave-on products containing humectants decreased skin dryness and reduced pruritus. Products with pH 4 improved the skin barrier. Application of skin protectants and structured skin care protocols decreased the severity of incontinence-associated dermatitis. Formulations containing glycerin and petrolatum reduced the incidence of skin tears. Thirty-five outcome domains were identified with nearly 100 different outcome measurement instruments.
CONCLUSION
Included studies showed substantial heterogeneity regarding design, interventions and outcomes. Basic skin care strategies including low-irritating cleansers and lipophilic humectant-containing leave-on products are helpful for treating dry skin and improving skin barrier in the aged. Lower pH of leave-on products improves the skin barrier. The number of different outcome domains was unexpectedly high. We recommend to identify critical outcome domains in the field of skin care to make trial results more comparable in the future and to measure possible performance differences between different skin care strategies and products.
Topics: Aged; Humans; Skin; Skin Care
PubMed: 31945604
DOI: 10.1016/j.ijnurstu.2019.103509 -
Journal of Cutaneous Medicine and... 2022Atopic dermatitis (AD) is a type 2 chronic skin disorder associated with systemic and psychosocial comorbidities decreasing the quality of life for many patients.... (Meta-Analysis)
Meta-Analysis Review
Atopic dermatitis (AD) is a type 2 chronic skin disorder associated with systemic and psychosocial comorbidities decreasing the quality of life for many patients. Dupilumab, a human monoclonal antibody that blocks interleukins IL-4 and IL-13, is a recently added systematic treatment option with an emerging evidence base. Here, we assessed the safety and efficacy of dupilumab in patients with AD. We conducted a systematic review and meta-analysis of placebo-controlled randomized clinical trials evaluating the safety and efficacy of dupilumab on AD-related outcomes including clinical symptoms, quality of life and adverse events (AE). Subgroup analysis was further performed in adults and children/adolescents. Fourteen trials were included: twelve in adults (n = 3,817) and two in children/adolescents (n = 618). Dupilumab decreased the Eczema Area Severity Index (EASI) score [standardized mean difference (SMD) = -0.98; 95% confidence interval (95% CI) = (-1.09, -0.88)], the percent change difference in Scoring Atopic Dermatitis (SCORAD) [mean difference (MD) = -31.56, 95% CI = (-33.75, -29.36)], and in pruritus Numeric Rating Scale (pNRS) [MD = -29.24, 95% CI = (-32.11, -26.37)]. It also achieved a reduction of at least ≥75% in the EASI score [Risk Ratio (RR) = 2.89, 95% CI = (2.47, 3.38)], the Investigator's Global Assessment (IGA) score ≤1 [RR = 3.47, 95% CI = (2.96, 4.06)] and eight additional endpoints with no signs of increased AE compared to placebo. In subgroup analysis, the results were concordant for both groups. Dupilumab improved clinical symptoms and quality of life in adults and children/adolescents with a safety profile comparable to placebo.
Topics: Adult; Adolescent; Child; Humans; Dermatitis, Atopic; Quality of Life; Injections, Subcutaneous; Severity of Illness Index; Treatment Outcome; Double-Blind Method
PubMed: 36214355
DOI: 10.1177/12034754221130969