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Autoimmunity Reviews Jul 2023Alopecia areata (AA) is an autoimmune non-scarring alopecia that affects the scalp or any hair-bearing areas in the body. The pathophysiology of AA is complex, but Th1,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alopecia areata (AA) is an autoimmune non-scarring alopecia that affects the scalp or any hair-bearing areas in the body. The pathophysiology of AA is complex, but Th1, Th2, and Th17 cytokines dysregulation, as well as chemokines, immunoglobulins and other biomarkers have been shown to play a role in the pathogenesis of the disease.
OBJECTIVE
To conduct a systematic review and Meta-analysis to identify biomarkers that reflect AA activity and severity that could be used to better assess disease activity and response in both trials and clinical practice.
METHODS
A literature search was conducted using the PUBMED, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to December 2021. Articles reporting on associations between AA and serum clinical biomarkers (cytokines, chemokines, antibodies, immunoglobulins, and others) were included. Serum biomarkers were identified in patients with AA and were correlated with disease severity and patient characteristics (ex. age, sex, comorbidities). The quality of the studies was assessed using the National Heart, Lung, and Blood Institute's Quality Assessment Tool for Case-Control Studies. Meta-analysis pooling of the standardized mean differences (SMD) by the method of Cohen using the common-effect inverse-variance model was performed. For the Meta-analysis, data was pulled for all the markers with a minimum of 4 studies with means and standard deviations. Analysis of data reported as Median with range or inter-quartile range (IQR) revealed that the data was too skewed to recommend calculation and use of mean with standard deviation (SD). If the data were not skewed, mean and SD were calculated.
RESULTS
One thousand seven hundred fourteen studies were screened, with 91 included, reporting on a total of 52 biomarkers. Meta-analyses revealed pooled SMD that were significant for interleukin 6 (IL6), C-reactive protein (CRP) and vitamin D.
CONCLUSIONS
Serum IL6 and CRP levels are significantly increased in patients with AA compared to healthy age and sex matched controls. Conversely, serum vitamn D levels are significantly decreased in patients with AA compared to healthy age and sex matched controls. This data has the potential to influence the clinical guidelines for the diagnostic workup of AA to include testing the serum levels of CRP and vitamin D.
Topics: Humans; Alopecia Areata; Interleukin-6; Biomarkers; Cytokines; Vitamin D; Chemokines; C-Reactive Protein; Vitamins
PubMed: 37087083
DOI: 10.1016/j.autrev.2023.103339 -
JAMA Dermatology Jan 2024Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions.
OBJECTIVE
To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions.
DATA SOURCES
PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023.
STUDY SELECTION
This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded.
DATA EXTRACTION AND SYNTHESIS
This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO.
MAIN OUTCOMES AND MEASURES
Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE.
RESULTS
The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.
Topics: Humans; Male; Adult; Janus Kinase Inhibitors; Venous Thromboembolism; Arthritis, Rheumatoid; Dermatitis, Atopic; Treatment Outcome
PubMed: 37910098
DOI: 10.1001/jamadermatol.2023.4090 -
The Cochrane Database of Systematic... Oct 2023Alopecia areata is an autoimmune disease leading to nonscarring hair loss on the scalp or body. There are different treatments including immunosuppressants, hair growth... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alopecia areata is an autoimmune disease leading to nonscarring hair loss on the scalp or body. There are different treatments including immunosuppressants, hair growth stimulants, and contact immunotherapy.
OBJECTIVES
To assess the benefits and harms of the treatments for alopecia areata (AA), alopecia totalis (AT), and alopecia universalis (AU) in children and adults.
SEARCH METHODS
The Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO ICTRP were searched up to July 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated classical immunosuppressants, biologics, small molecule inhibitors, contact immunotherapy, hair growth stimulants, and other therapies in paediatric and adult populations with AA.
DATA COLLECTION AND ANALYSIS
We used the standard procedures expected by Cochrane including assessment of risks of bias using RoB2 and the certainty of the evidence using GRADE. The primary outcomes were short-term hair regrowth ≥ 75% (between 12 and 26 weeks of follow-up), and incidence of serious adverse events. The secondary outcomes were long-term hair regrowth ≥ 75% (greater than 26 weeks of follow-up) and health-related quality of life. We could not perform a network meta-analysis as very few trials compared the same treatments. We presented direct comparisons and made a narrative description of the findings.
MAIN RESULTS
We included 63 studies that tested 47 different treatments in 4817 randomised participants. All trials used a parallel-group design except one that used a cross-over design. The mean sample size was 78 participants. All trials recruited outpatients from dermatology clinics. Participants were between 2 and 74 years old. The trials included patients with AA (n = 25), AT (n = 1), AU (n = 1), mixed cases (n = 31), and unclear types of alopecia (n = 4). Thirty-three out of 63 studies (52.3%) reported the proportion of participants achieving short-term hair regrowth ≥ 75% (between 12 and 26 weeks). Forty-seven studies (74.6%) reported serious adverse events and only one study (1.5%) reported health-related quality of life. Five studies (7.9%) reported the proportion of participants with long-term hair regrowth ≥ 75% (greater than 26 weeks). Amongst the variety of interventions found, we prioritised some groups of interventions for their relevance to clinical practice: systemic therapies (classical immunosuppressants, biologics, and small molecule inhibitors), and local therapies (intralesional corticosteroids, topical small molecule inhibitors, contact immunotherapy, hair growth stimulants and cryotherapy). Considering only the prioritised interventions, 14 studies from 12 comparisons reported short-term hair regrowth ≥ 75% and 22 studies from 10 comparisons reported serious adverse events (18 reported zero events and 4 reported at least one). One study (1 comparison) reported quality of life, and two studies (1 comparison) reported long-term hair regrowth ≥ 75%. For the main outcome of short-term hair regrowth ≥ 75%, the evidence is very uncertain about the effect of oral prednisolone or cyclosporine versus placebo (RR 4.68, 95% CI 0.57 to 38.27; 79 participants; 2 studies; very low-certainty evidence), intralesional betamethasone or triamcinolone versus placebo (RR 13.84, 95% CI 0.87 to 219.76; 231 participants; 1 study; very low-certainty evidence), oral ruxolitinib versus oral tofacitinib (RR 1.08, 95% CI 0.77 to 1.52; 80 participants; 1 study; very low-certainty evidence), diphencyprone or squaric acid dibutil ester versus placebo (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very-low-certainty evidence), diphencyprone or squaric acid dibutyl ester versus topical minoxidil (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very low-certainty evidence), diphencyprone plus topical minoxidil versus diphencyprone (RR 0.67, 95% CI 0.13 to 3.44; 30 participants; 1 study; very low-certainty evidence), topical minoxidil 1% and 2% versus placebo (RR 2.31, 95% CI 1.34 to 3.96; 202 participants; 2 studies; very low-certainty evidence) and cryotherapy versus fractional CO2 laser (RR 0.31, 95% CI 0.11 to 0.86; 80 participants; 1 study; very low-certainty evidence). The evidence suggests oral betamethasone may increase short-term hair regrowth ≥ 75% compared to prednisolone or azathioprine (RR 1.67, 95% CI 0.96 to 2.88; 80 participants; 2 studies; low-certainty evidence). There may be little to no difference between subcutaneous dupilumab and placebo in short-term hair regrowth ≥ 75% (RR 3.59, 95% CI 0.19 to 66.22; 60 participants; 1 study; low-certainty evidence) as well as between topical ruxolitinib and placebo (RR 5.00, 95% CI 0.25 to 100.89; 78 participants; 1 study; low-certainty evidence). However, baricitinib results in an increase in short-term hair regrowth ≥ 75% when compared to placebo (RR 7.54, 95% CI 3.90 to 14.58; 1200 participants; 2 studies; high-certainty evidence). For the incidence of serious adverse events, the evidence is very uncertain about the effect of topical ruxolitinib versus placebo (RR 0.33, 95% CI 0.01 to 7.94; 78 participants; 1 study; very low-certainty evidence). Baricitinib and apremilast may result in little to no difference in the incidence of serious adverse events versus placebo (RR 1.47, 95% CI 0.60 to 3.60; 1224 participants; 3 studies; low-certainty evidence). The same result is observed for subcutaneous dupilumab compared to placebo (RR 1.54, 95% CI 0.07 to 36.11; 60 participants; 1 study; low-certainty evidence). For health-related quality of life, the evidence is very uncertain about the effect of oral cyclosporine compared to placebo (MD 0.01, 95% CI -0.04 to 0.07; very low-certainty evidence). Baricitinib results in an increase in long-term hair regrowth ≥ 75% compared to placebo (RR 8.49, 95% CI 4.70 to 15.34; 1200 participants; 2 studies; high-certainty evidence). Regarding the risk of bias, the most relevant issues were the lack of details about randomisation and allocation concealment, the limited efforts to keep patients and assessors unaware of the assigned intervention, and losses to follow-up.
AUTHORS' CONCLUSIONS
We found that treatment with baricitinib results in an increase in short- and long-term hair regrowth compared to placebo. Although we found inconclusive results for the risk of serious adverse effects with baricitinib, the reported small incidence of serious adverse events in the baricitinib arm should be balanced with the expected benefits. We also found that the impact of other treatments on hair regrowth is very uncertain. Evidence for health-related quality of life is still scant.
Topics: Adult; Humans; Child; Child, Preschool; Adolescent; Young Adult; Middle Aged; Aged; Alopecia Areata; Minoxidil; Network Meta-Analysis; Immunosuppressive Agents; Prednisolone; Betamethasone; Cyclosporins; Biological Products
PubMed: 37870096
DOI: 10.1002/14651858.CD013719.pub2 -
American Journal of Clinical Dermatology Nov 2023Alopecia areata (AA) is a complex autoimmune condition resulting in nonscarring hair loss. In recent years, many studies have provided new evidence on comorbid diseases... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alopecia areata (AA) is a complex autoimmune condition resulting in nonscarring hair loss. In recent years, many studies have provided new evidence on comorbid diseases present in patients with AA. However, some studies have conflicting results, and analyses conducting a comprehensive approach are lacking.
OBJECTIVE
The aim of our study was to provide an updated systematic review and meta-analysis of medical comorbidities associated with AA.
METHODS
We searched PubMed, Embase, and Web of Science for case-control, cross-sectional, and cohort studies investigating medical comorbidities in AA published from inception through 1 February 2023.
RESULTS
We screened 3428 abstracts and titles and reviewed 345 full text articles for eligibility. Ultimately, 102 studies were analyzed, comprising 680,823 patients with AA and 72,011,041 healthy controls. Almost all included studies (100 of 102 studies) were of satisfactory to high quality (Newcastle-Ottawa scale score ≥ 4). Among patients with AA, comorbidities with the highest odds ratios (OR) compared with healthy controls and data available from more than one study included vitamin D deficiency (OR 10.13, 95% CI 4.24-24.20), systemic lupus erythematous (OR 5.53, 95% CI 3.31-9.23), vitiligo (OR 5.30, 95% CI 1.86-15.10), metabolic syndrome (OR 5.03, 95% CI 4.18-6.06), and Hashimoto's thyroiditis (OR 4.31, 95% CI 2.51-7.40). AA may be a protective factor for certain disorders, for which the AA group had lower odds compared with healthy controls, such as irritable bowel syndrome (OR 0.38, 95% CI 0.14-0.99) and colorectal cancer (OR 0.61, 95% CI 0.42-0.89).
CONCLUSION
These findings corroborate and contextualize the risks across comorbidities for patients with AA. Further work should be done to identify the underlying pathophysiology and understand appropriate screening criteria.
Topics: Humans; Alopecia Areata; Cross-Sectional Studies; Comorbidity; Autoimmune Diseases
PubMed: 37464249
DOI: 10.1007/s40257-023-00805-4 -
Dermatitis : Contact, Atopic,... 2024This systematic review and meta-analysis aimed to explore the association between atopic Dermatitis® (AD) and alopecia areata (AA). A comprehensive search was conducted... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to explore the association between atopic Dermatitis® (AD) and alopecia areata (AA). A comprehensive search was conducted in PubMed, Embase, Cochrane, and Web of Science from the inception of each database to November 10, 2022 for relevant studies. As there is a potential bilateral association between the 2 diseases, we assessed the prevalence/incidence of AA in patients with AD and the prevalence/incidence of AD in patients with AA. A total of 29 studies involving 11,233,448 participants were included in this analysis. AA was the exposure factor in 23 studies, AD in 7 studies, and both in 1 study. The meta-analysis revealed that the prevalence of AD was 11.2% (7.7%-15.1%) in patients with AA, and the prevalence of AA was 3.2% (95% confidence interval [CI]: 0.0%-11.5%) in patients with AD. The incidence of AD in AA patients was found to vary with age ( = 0.07). Based on 7 studies, there was a significant association between AD and AA when AA was the exposure factor [odds ratio, OR, = 4.537 (95% CI: 2.409-8.544)]; based on 10 studies, there was also a significant association between AD and AA when AD was the exposure factor [OR = 2.643 (95% CI: 1.737-3.995)]. In conclusion, this meta-analysis demonstrated the 2-way association between AD and AA, providing a clinical reference for disease prevention and control.
Topics: Alopecia Areata; Humans; Dermatitis, Atopic; Prevalence; Incidence
PubMed: 37471232
DOI: 10.1089/derm.2023.0114 -
Journal of the American Academy of... Jan 2024
Topics: Humans; Alopecia Areata
PubMed: 37207950
DOI: 10.1016/j.jaad.2023.05.022 -
Dermatology and Therapy Dec 2023Treatments for alopecia areata (AA) have traditionally been prescribed off-label, and there has been no universal agreement on how to best manage the condition.... (Review)
Review
Treatments for alopecia areata (AA) have traditionally been prescribed off-label, and there has been no universal agreement on how to best manage the condition. Baricitinib is the first oral selective Janus kinase (JAK) inhibitor approved for the treatment of adults with severe AA. As a better understanding of the evidence supporting the management of AA in clinical practice is needed, we conducted a systematic literature review and subsequent narrative review to describe available evidence pertaining to the efficacy and tolerability of treatments currently recommended for adults with moderate-to-severe forms of AA. From 2557 identified records, a total of 53 records were retained for data extraction: 9 reported data from 7 randomized controlled trials (RCTs) versus placebo, and 44 reported data from unique RCTs with no placebo arm, non-randomized trials, or observational studies. Across drug classes, data were reported heterogeneously, with little consistency of data collection or clinical endpoints used. The most robust evidence was for the JAK inhibitor class, in particular the JAK1/JAK2 inhibitor baricitinib. Five RCTs (three for baricitinib) demonstrated a consistent benefit of JAK inhibitor therapy over placebo across various clinical outcomes in adult patients with at least 50% scalp hair loss. Overall, hair regrowth varied widely for the other drug classes and was generally low for patients with moderate-to-severe AA. Relapses were commonly observed during treatment and upon discontinuation. Adverse effects were generally consistent with the known safety profile of each intervention. The heterogeneity observed prevented the conduct of a network meta-analysis or an indirect comparison of different treatments. We found that the current management of patients with moderate-to-severe AA often relies on the use of treatments that have not been well evaluated in clinical trials. The most robust evidence identified supported the use of baricitinib, and other oral JAK inhibitors, in patients with severe AA.
PubMed: 37833617
DOI: 10.1007/s13555-023-01044-5 -
International Journal of Dermatology Nov 2023
PubMed: 37391898
DOI: 10.1111/ijd.16773 -
Journal of the American Academy of... May 2024
Review
PubMed: 38796079
DOI: 10.1016/j.jaad.2024.05.037 -
The British Journal of Dermatology Feb 2024Alopecia areata (AA) is a chronic autoimmune disease that leads to a high psychiatric, economic, and systemic disease burden. A comprehensive understanding of AA...
BACKGROUND
Alopecia areata (AA) is a chronic autoimmune disease that leads to a high psychiatric, economic, and systemic disease burden. A comprehensive understanding of AA epidemiology is essential for evaluating healthcare source utilization; however, there is a lack of systematic approach for summarizing epidemiologic data on AA.
OBJECTIVES
To systematically investigate the global, regional, and national incidence and prevalence of AA.
METHODS
A structured search was conducted using the Ovid MEDLINE, EMBASE, Cochrane Library, Web of Science, SciELO, and Korean journal databases from their inception date to October 4, 2023. Studies that reported the prevalence or incidence of AA were included. We used a Bayesian hierarchical linear mixed model to analyse the prevalence estimates. The primary outcomes of our study were the global, regional, and national prevalence of physician-diagnosed AA for overall population, adults, and children. The incidence data were summarised descriptively.
RESULTS
In total, 88 studies from 28 countries were included in the analysis. The reported incidence of alopecia areata tended to be higher in adults aged 19-50 years, and this trend was consistent with its estimated prevalence. The reported prevalence in overall population tended to be higher in men compared to in women. The estimated lifetime prevalence of AA was 0.10% (95% credible intervals, 0.03%-0.39%) in the general population worldwide, 0.12% (95% credible intervals, 0.02%-0.52%) in adults, and 0.03% (95% credible intervals, 0.01%-0.12%) in children. The estimated prevalence was highest in the Asian region and lowest in the African region.
CONCLUSIONS
In this study, 48% of the total Global Burden of Disease regions had insufficient data reporting the prevalence or incidence of AA. Further studies are needed to provide epidemiological information on middle- and low-income countries. Our study can serve as a crucial reference in terms of healthcare policy decisions.
PubMed: 38332643
DOI: 10.1093/bjd/ljae058