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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 -
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 -
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 -
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 -
Journal of the American Academy of... Feb 2019Previous studies found conflicting results about the commonality of different atopic dermatitis (AD) signs and symptoms. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies found conflicting results about the commonality of different atopic dermatitis (AD) signs and symptoms.
OBJECTIVE
To determine the prevalences of AD characteristics and differences by region and age.
METHODS
A systematic review was performed of all published studies in MEDLINE, EMBASE, SCOPUS, LILACS, Cochrane, China National Knowledge Infrastructure, Taiwan Electronic Periodical Services, and CiNii that analyzed the proportion of AD characteristics. Two reviewers performed a review study titles and/or abstracts and data abstraction.
RESULTS
In all, 101 studies reported proportion of AD features with sufficient data for meta-analysis. The most prevalent AD features were pruritus, lichenification, and xerosis. There were differences in AD characteristics by study region. Flexural involvement was less commonly reported in India, the Americas, and Iran. Studies from East Asian reported more erythroderma and truncal, extensor, scalp, and auricular involvement. Studies from Southeast Asia reported more exudative eczema, truncal involvement, lichenification, and prurigo nodularis. Studies from Iran reported more head, face, and neck involvement; pityriasis alba; and xerosis. Studies from Africa reported more papular lichenoid lesions, palmar hyperlinearity, ichthyosis, and orbital darkening.
LIMITATIONS
Heterogeneity between studies and limited reporting of certain AD clinical characteristics.
CONCLUSIONS
AD characteristics are heterogeneous and vary by region and age.
Topics: Adolescent; Adult; Age of Onset; Biopsy, Needle; Child; Dermatitis, Atopic; Disease Progression; Female; Humans; Immunohistochemistry; Internationality; Male; Prevalence; Prognosis; Risk Assessment; Severity of Illness Index; Young Adult
PubMed: 30287309
DOI: 10.1016/j.jaad.2018.09.035 -
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 -
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 -
Dermatology and Therapy May 2022The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data....
INTRODUCTION
The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD.
METHODS
The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis.
RESULTS
Of 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily.
DISCUSSION
Many factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient's treatment.
CONCLUSION
Upadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12-16 weeks of therapy in AD.
PubMed: 35435637
DOI: 10.1007/s13555-022-00721-1 -
Micronized Purified Flavonoid Fraction in Hemorrhoid Disease: A Systematic Review and Meta-Analysis.Advances in Therapy Jun 2020Hemorrhoidal disease (HD) is a common and recurrent problem for many adults worldwide. Venoactive drugs, such as micronized purified flavonoid fraction (MPFF; Daflon),... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Hemorrhoidal disease (HD) is a common and recurrent problem for many adults worldwide. Venoactive drugs, such as micronized purified flavonoid fraction (MPFF; Daflon), have been used to treat HD and their clinical benefits have been demonstrated in previous meta-analyses of clinical trials. The aim of this study was to evaluate the efficacy of MPFF across the broader spectrum of signs and symptoms following treatment of patients with HD.
METHODS
We performed a systematic review of the literature to identify randomized clinical trials in which MPFF treatment was compared to placebo or no treatment for acute HD or for relief of symptoms after patients had undergone medical management or a surgical procedure to remove hemorrhoids. The main endpoints investigated were bleeding, pain, pruritus, discharge or leakage, and overall improvement. There was no limit on treatment duration.
RESULTS
From 351 unique records retrieved, 11 studies reported in 13 articles were included. On the basis of findings from qualitative analysis, MPFF was reported in most studies to be beneficial in treating bleeding, pain, pruritus, anal discharge/leakage, and tenesmus, and in overall improvement. Quantitative meta-analysis of four studies indicated that MPFF treatment provided significant benefits for bleeding (odds ratio [OR] 0.082, 95% confidence interval [CI] 0.027-0.250; P < 0.001), discharge/leakage (OR 0.12, 95% CI 0.04-0.42; P < 0.001), and overall improvement according to patients (OR 5.25, 95% CI 2.58-10.68; P < 0.001) and investigators (OR 5.51, 95% CI 2.76-11.0; P < 0.001). MPFF also tended to decrease pain (OR 0.11, 95% CI 0.01-1.11; P = 0.06).
CONCLUSION
Taken together, these results suggest that MPFF treatment can improve the most important signs and symptoms of HD.
Topics: Adult; Aged; Aged, 80 and over; Diosmin; Female; Hemorrhoids; Humans; Male; Middle Aged; Odds Ratio; Risk Assessment
PubMed: 32399811
DOI: 10.1007/s12325-020-01353-7 -
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