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Journal of the European Academy of... Apr 2024Alopecia areata is an autoimmune form of non-scarring hair loss. It is usually characterized by limited areas of hair loss. However, the disease may progress to complete... (Review)
Review
Alopecia areata is an autoimmune form of non-scarring hair loss. It is usually characterized by limited areas of hair loss. However, the disease may progress to complete scalp and body hair loss (alopecia totalis, alopecia universalis). In patients with alopecia areata hair loss significantly impacts the quality of life. Children and adolescents with alopecia areata often experience bullying, including physical aggression. The disease severity evaluation tools used in clinical practice are: the Severity of Alopecia Tool (SALT) score and the Alopecia Areata Scale (AAS). A SALT score equal to or greater than 20 constitutes a commonly accepted indication for systemic therapy in alopecia areata. When using the AAS, moderate to severe alopecia areata should be considered a medical indication for systemic treatment. Currently, the only two EMA-approved medications for alopecia areata are baricitinib (JAK 1/2 inhibitor) for adults and ritlecitinib (JAK 3/TEC inhibitor) for individuals aged 12 and older. Both are EMA-approved for patients with severe alopecia areata. Other systemic medications used off-label in alopecia areata include glucocorticosteroids, cyclosporine, methotrexate and azathioprine. Oral minoxidil is considered an adjuvant therapy with limited data confirming its possible efficacy. This consensus statement is to outline a systemic treatment algorithm for alopecia areata, indications for systemic treatment, available therapeutic options, their efficacy and safety, as well as the duration of the therapy.
Topics: Adult; Adolescent; Child; Humans; Alopecia Areata; Quality of Life; Alopecia; Minoxidil; Azathioprine; Janus Kinase Inhibitors
PubMed: 38169088
DOI: 10.1111/jdv.19768 -
Journal of the American Academy of... Aug 2023Janus kinase (JAK) inhibitors have ushered in a new era in alopecia areata (AA). Historically, moderate-to-severe AA was refractory to treatment. JAK inhibitors have... (Review)
Review
Janus kinase (JAK) inhibitors have ushered in a new era in alopecia areata (AA). Historically, moderate-to-severe AA was refractory to treatment. JAK inhibitors have changed that; now, treatment of moderate-to-severe AA is possible. Here, we briefly review the history of and rationale for JAK inhibitor treatment of AA, phase 3 clinical trial data, and considerations regarding differences among JAK inhibitors, safety, and patient selection.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Patient Selection; Clinical Trials, Phase III as Topic
PubMed: 37591562
DOI: 10.1016/j.jaad.2023.05.049 -
Journal of Dermatological Science Dec 2023Alopecia areata (AA) is a common, acquired, and nonscarring type of hair loss that affects people of every generation and is intractable in severe and relapsing cases.... (Review)
Review
BACKGROUND
Alopecia areata (AA) is a common, acquired, and nonscarring type of hair loss that affects people of every generation and is intractable in severe and relapsing cases. Patients with AA, especially those with greater scalp involvement, have poor health-related quality-of-life scores.
PURPOSE
Following our previous review article in the April 2017 issue of the Journal of Dermatological Science, we aim to provide a pair of review articles on recent progress in multidisciplinary approaches to AA.
MAIN FINDINGS
We found more than 1800 publications on AA from July 2016 to December 2022.
CONCLUSIONS
In this review, we focused on the latest information on the epidemiology, comorbidities, and pathogenesis of AA.
Topics: Humans; Alopecia Areata; Alopecia; Comorbidity; Quality of Life; Recurrence
PubMed: 37833164
DOI: 10.1016/j.jdermsci.2023.09.008 -
JAMA Network Open Oct 2023Multiple cases of autoimmune and autoinflammatory diseases after COVID-19 have been reported. However, their incidences and risks have rarely been quantified.
IMPORTANCE
Multiple cases of autoimmune and autoinflammatory diseases after COVID-19 have been reported. However, their incidences and risks have rarely been quantified.
OBJECTIVE
To investigate the incidences and risks of autoimmune and autoinflammatory connective tissue disorders after COVID-19.
DESIGN, SETTING, AND PARTICIPANTS
This was a retrospective population-based study conducted between October 8, 2020, and December 31, 2021, that used nationwide data from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort and included individuals who received a diagnosis of COVID-19 via polymerase chain reaction testing and a control group with no evidence of COVID-19 identified from National Health Insurance Service of Korea cohort. Data analysis was conducted from September 2022 to August 2023.
EXPOSURES
Receipt of diagnosis of COVID-19.
MAIN OUTCOMES AND MEASURES
The primary outcomes were the incidence and risk of autoimmune and autoinflammatory connective tissue disorders following COVID-19. A total of 32 covariates, including demographics, socioeconomic statuses, lifestyle factors, and comorbidity profiles, were balanced through inverse probability weighting. The incidences and risks of autoimmune and autoinflammatory connective tissue disorders were compared between the groups using multivariable Cox proportional hazard analyses.
RESULTS
A total of 354 527 individuals with COVID-19 (mean [SD] age, 52.24 [15.55] years; 179 041 women [50.50%]) and 6 134 940 controls (mean [SD] age, 52.05 [15.63] years; 3 074 573 women [50.12%]) were included. The risks of alopecia areata (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.05-1.19), alopecia totalis (aHR, 1.74; 95% CI, 1.39-2.17), antineutrophil cytoplasmic antibody-associated vasculitis (aHR, 2.76; 95% CI, 1.64-4.65), Crohn disease (aHR, 1.68; 95% CI, 1.31-2.15), and sarcoidosis (aHR, 1.59; 95% CI, 1.00-2.52) were higher in the COVID-19 group. The risks of alopecia totalis, psoriasis, vitiligo, vasculitis, Crohn disease, ulcerative colitis, rheumatoid arthritis, adult-onset Still disease, Sjögren syndrome, ankylosing spondylitis, and sarcoidosis were associated with the severity of COVID-19.
CONCLUSIONS AND RELEVANCE
In this retrospective cohort study, COVID-19 was associated with a substantial risk for autoimmune and autoinflammatory connective tissue disorders, indicating that long-term management of patients with COVID-19 should include evaluation for such disorders.
Topics: Adult; Humans; Female; Middle Aged; Retrospective Studies; Crohn Disease; COVID-19; Connective Tissue; Sarcoidosis; Alopecia; Vasculitis
PubMed: 37801317
DOI: 10.1001/jamanetworkopen.2023.36120 -
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 -
Journal of the American Academy of... Oct 2023Data on the association between the development of autoimmune diseases and COVID-19 vaccination are limited.
BACKGROUND
Data on the association between the development of autoimmune diseases and COVID-19 vaccination are limited.
OBJECTIVE
To investigate the incidence and risk of autoimmune connective tissue disorders following mRNA-based COVID-19 vaccination.
METHODS
This nationwide population-based study was conducted in South Korea. Individuals who received vaccination between September 8, 2020-December 31, 2021, were identified. Historical prepandemic controls were matched for age and sex in 1:1 ratio. The incidence rate and risk of disease outcomes were compared.
RESULTS
A total of 3,838,120 vaccinated individuals and 3,834,804 controls without evidence of COVID-19 were included. The risk of alopecia areata, alopecia totalis, primary cicatricial alopecia, psoriasis, vitiligo, anti-neutrophil cytoplasmic antibody-associated vasculitis, sarcoidosis, Behcet disease, Crohn disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren syndrome, ankylosing spondylitis, dermato/polymyositis, and bullous pemphigoid was not significantly higher in vaccinated individuals than in controls. The risk was comparable according to age, sex, type of mRNA-based vaccine, and cross-vaccination status.
LIMITATIONS
Possible selection bias and residual confounders.
CONCLUSION
These findings suggest that most autoimmune connective tissue disorders are not associated with a significant increase in risk. However, caution is necessary when interpreting results for rare outcomes due to limited statistical power.
Topics: Humans; COVID-19 Vaccines; COVID-19; Autoimmune Diseases; Connective Tissue Diseases; Alopecia Areata; Vaccination; Connective Tissue
PubMed: 37187424
DOI: 10.1016/j.jaad.2023.05.017 -
JAMA Dermatology Nov 2023Alopecia areata (AA) is characterized by hair loss ranging from patches of hair loss to more extensive forms, including alopecia totalis (AT) and alopecia universalis...
IMPORTANCE
Alopecia areata (AA) is characterized by hair loss ranging from patches of hair loss to more extensive forms, including alopecia totalis (AT) and alopecia universalis (AU). There is a lack of consensus for treatment. Understanding current practice patterns could help the identification of treatment needs and development of standards of care.
OBJECTIVE
To review treatment patterns for adults with AA in the US between 2015 and 2020.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used medicine and pharmacy claims for commercially insured individuals from the IBM MarketScan Research Database to assess adults (≥18 years) newly treated for AA between October 15, 2015, and February 28, 2020. Alopecia areata was identified based on having at least 1 diagnosis of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code L63.x. Patients were required to have at least 365 days of continuous health plan enrollment before and after the cohort entry date. Patients were required to be free of AA diagnosis codes 365 days before the cohort entry date. Statistical analyses were conducted between 2019 and 2023.
MAIN OUTCOMES AND MEASURES
Main outcomes were treatment patterns for all patients with AA and subgroups of (1) patients with AT or AU and (2) those cared for by a dermatologist on the cohort entry date. Longitudinal therapy course during the first year after the diagnosis was also examined.
RESULTS
The study cohort consisted of 45 483 individuals (mean [SD] age, 43.8 [14.2] years; 29 903 [65.7%] female). During the year of follow-up, 30 217 patients (66.4%) received at least 1 AA treatment. The most common treatments were intralesional (19 014 [41.8%]), topical (18 604 [40.9%]), intramuscular (17 328 [38.1%]), and oral (9378 [20.6%]) corticosteroids. Compared with patients without AT or AU, patients with AT or AU a lower frequency of intralesional steroid (359 [11.1%] vs 18 655 [44.1%], P < .001) and higher frequency of topical corticosteroid (817 [25.4%] vs 17 787 [42.1%], P < .001) use. Almost half of patients (21 489 [47.2%]) received no treatment on the day of diagnosis. By 12 months, 32 659 (71.8%) were not receiving any treatment, making no treatment the largest study group.
CONCLUSIONS AND RELEVANCE
In this large cohort study of commercially insured individuals, corticosteroids were the most commonly used treatment for adults with AA between 2015 and 2020. At 365 days after diagnosis, more than two-thirds of patients were no longer receiving any AA treatment. Further studies are needed to understand the reasons for the absence of treatment.
Topics: Adult; Humans; Female; Male; Alopecia Areata; Retrospective Studies; Cohort Studies; Alopecia; Adrenal Cortex Hormones
PubMed: 37728940
DOI: 10.1001/jamadermatol.2023.3109 -
Acta Dermato-venereologica Aug 2023Alopecia areata is an autoimmune disorder characterized by hair loss, for which there are few treatment options. This claims-based study characterized recent real-world...
Alopecia areata is an autoimmune disorder characterized by hair loss, for which there are few treatment options. This claims-based study characterized recent real-world treatment patterns among patients in the USA with alopecia areata, including the subtypes alopecia totalis and alopecia universalis, in the first year after diagnosis of an episode of alopecia areata. Approximately 5% of all patients (adults (age ≥ 18 years), n = 7,703; adolescents (age 12-17 years), n = 595) had alopecia totalis or alopecia universalis. Corticosteroids were the most common first-line (1L) and second-line (2L) treatments. The mean time from diagnosis of alopecia areata to initiation of 1L treatment was 2.2 days for adults and 2.6 days for adolescents; mean 1L duration was 76.9 and 64.3 days, respectively. For adults (57.5%) and adolescents (59.7%) with 2L therapy, the mean time from 1L discontinuation to 2L initiation was 57.2 and 53.6 days, respectively; the mean duration of 2L treatment was 55.5 and 50.1 days, respectively. More patients with vs without alopecia totalis or alopecia universalis initiated 2L therapy (adults: 71.9% vs 56.8%; adolescents: 71.4% vs 58.9%). The proportion of days covered during the first year post-diagnosis was 36.7% (adults) and 34.1% (adolescents). These results highlight the substantial disease burden of alopecia areata and a need for more effective treatments.
Topics: Adolescent; Adult; Humans; United States; Child; Alopecia Areata; Insurance Claim Review; Retrospective Studies
PubMed: 37622204
DOI: 10.2340/actadv.v103.12445 -
Expert Opinion on Investigational Drugs May 2024Alopecia areata (AA) is an immune-mediated disease that causes non-scarring hair loss. While acute, solitary patches often spontaneously remit, developing secondary... (Review)
Review
INTRODUCTION
Alopecia areata (AA) is an immune-mediated disease that causes non-scarring hair loss. While acute, solitary patches often spontaneously remit, developing secondary patches or failure of the disease to resolve within 6-12 months predicts a poor prognosis, with an increased risk of alopecia totalis or universalis. Chronic AA increases the risk of depression and suicidality and reduces quality of life. Treatment options for chronic or acute diffuse AA were previously limited to corticosteroids and traditional immunomodulators. Two Janus Kinase (JAK) inhibitors are now approved for the treatment of chronic AA.
AREAS COVERED
The results of landmark phase 3 trials for three JAK inhibitors, baricitinib, ritlecitinib, and deuruxolitinib are discussed. Evidence for other JAK inhibitors, biologics, and phosphodiesterase-4 inhibitors are also presented. Therapies currently undergoing clinical trials are listed.
EXPERT OPINION
JAK inhibitors are a safe and efficacious treatment of moderate-to-severe AA. Early intervention, regardless of severity, allows for improved treatment efficacy. It is uncertain how long patients should remain on JAK inhibitors; discontinuation often leads to relapse. A black-box warning for JAK inhibitors was extrapolated from safety data in a rheumatoid arthritis cohort; recent meta-analyses of JAK inhibitors used in dermatology cohorts do not demonstrate the same risk profile.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Drugs, Investigational; Quality of Life; Severity of Illness Index; Animals; Chronic Disease; Prognosis; Drug Development
PubMed: 38682280
DOI: 10.1080/13543784.2024.2348062