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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 -
Frontiers in Immunology 2023Alopecia areata (AA) is an immune disease characterized by non-scarring hair loss. With the widespread application of JAK inhibitors in immune-related diseases,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alopecia areata (AA) is an immune disease characterized by non-scarring hair loss. With the widespread application of JAK inhibitors in immune-related diseases, attention is being given to their role in the treatment of AA. However, it is unclear which JAK inhibitors have a satisfactory or positive effect on AA. This network meta-analysis aimed to compare the efficacy and safety of different JAK inhibitors in the treatment of AA.
METHODS
The network meta-analysis was performed according to the PRISMA guidelines. We included randomized controlled trials as well as a small number of cohort studies. The differences in efficacy and safety between the treatment and control groups were compared.
RESULTS
Five randomized controlled trials, two retrospective studies, and two prospective studies involving 1689 patients were included in this network meta-analysis. In terms of efficacy, oral baricitinib and ruxolitinib significantly improved the response rate of patients compared to placebo [MD = 8.44, 95% CI (3.63, 19.63)] and [MD = 6.94, 95% CI, (1.72, 28.05)],respectively. Oral baricitinib treatment significantly improved the response rate compared to non-oral JAK inhibitor treatment [MD=7.56, 95% CI (1.32,43.36)]. Oral baricitinib, tofacitinib, and ruxolitinib treatments significantly improved the complete response rate compared to placebo [MD = 12.21, 95% CI (3.41, 43.79)], [MD = 10.16, 95% CI (1.02, 101.54)], and [MD = 9.79, 95% CI, (1.29, 74.27)], respectively. In terms of safety, oral baricitinib, tofacitinib, and ruxolitinib treatments significantly reduced treatment-emergent adverse event rates compared with conventional steroid treatment [MD = 0.08, 95% CI (0.02, 0.42)], [MD = 0.14, 95% CI (0.04, 0.55)], and [MD = 0.35, 95% CI, (0.14, 0.88)], respectively.
CONCLUSION
Oral baricitinib and ruxolitinib are excellent options for the treatment of AA owing to their good efficacy and safety profiles. In contrast, non-oral JAK inhibitors do not appear to have satisfactory efficacy in treating AA. However, further studies are required to verify the optimal dose of JAK inhibitors for AA therapy.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Network Meta-Analysis; Prospective Studies; Retrospective Studies; Randomized Controlled Trials as Topic
PubMed: 37138884
DOI: 10.3389/fimmu.2023.1152513 -
Clinical Drug Investigation May 2023Janus kinase (JAK) inhibitors are emerging as a therapeutic option for alopecia areata. The risk of potential adverse events is currently debated. In particular, several...
BACKGROUND AND OBJECTIVES
Janus kinase (JAK) inhibitors are emerging as a therapeutic option for alopecia areata. The risk of potential adverse events is currently debated. In particular, several safety data for JAK inhibitors are extrapolated from a single study in elderly patients with rheumatoid arthritis treated with tofacitinib or adalimumab/etanercept as a comparator. The population of patients with alopecia areata is clinically and immunologically different from persons with rheumatoid arthritis and tumor necrosis factor (TNF) inhibitors are not effective in these patients. The objective of this systematic review was to analyze available data on the safety of various JAK inhibitors in patients with alopecia areata.
METHODS
The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature review was performed by searching PubMed, Scopus and EBSCO databases with the last search on March 13, 2023.
RESULTS
In total, 36 studies were included. The frequency and odds ratio (OR) for most common adverse events versus placebo were: for baricitinib hypercholesterolemia (18.2% vs 10.5%, OR = 1.9) and headache (6.1% vs 5.1%, OR = 1.2), for brepocitinib elevated creatinine level (27.7% vs 4.3%, OR = 8.6) and acne (10.6% vs 4.3%, OR = 2.7), for ritlecitinib acne (10.4% vs 4.3%, OR = 2.6) and headache (12.5% vs 10.6%, OR = 1.2) and for deuruxolitinib headache (21.4% vs 9.1%, OR = 2.7) and acne (13.6% vs 4.5%, OR = 3.3). The respective numbers for upper respiratory infections were: baricitinib (7.3% vs 7.0%, OR = 1.0) and brepocitinib (23.4% vs 10.6%, OR = 2.6); for nasopharyngitis: ritlecitinib (12.5% vs 12.8%, OR = 1.0) and deuruxolitinib (14.6% vs 2.3%, OR = 7.3).
CONCLUSIONS
The most common side effects of JAK inhibitors in patients with alopecia areata were headache and acne. The OR for upper respiratory tract infections varied from over 7-fold increased to comparable to placebo. The risk of serious adverse events was not increased.
Topics: Humans; Aged; Janus Kinase Inhibitors; Alopecia Areata; Protein Kinase Inhibitors; Arthritis, Rheumatoid; Alopecia
PubMed: 37138134
DOI: 10.1007/s40261-023-01260-z -
Dermatology (Basel, Switzerland) 2023Immune-mediated melanocyte-related pathogenesis in alopecia areata (AA) may cause sensorineural hearing loss (SNHL). However, the relation between AA and SNHL has been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Immune-mediated melanocyte-related pathogenesis in alopecia areata (AA) may cause sensorineural hearing loss (SNHL). However, the relation between AA and SNHL has been unclear. Therefore, we aimed to investigate this association between AA and SNHL.
METHODS
We performed a systematic review and searched MEDLINE and Embase on July 25, 2022, for cross-sectional, case-control, or cohort studies that examined the association of AA with SNHL. The Newcastle-Ottawa Scale was used to evaluate their risk of bias. A random-effects model meta-analysis was performed to obtain the mean differences in frequency-specific hearing thresholds between AA patients and age-matched healthy controls and the pooled odds ratio for SNHL in relation to AA.
RESULTS
We included 5 case-control studies and 1 cohort study, with none of them rated with high risk of biases. The meta-analysis showed AA patients had significantly higher mean differences in pure-tone hearing thresholds at 4,000 Hz and 12,000-12,500 Hz. The meta-analysis also found increased odds for SNHL among patients with AA (OR: 3.18; 95% CI: 2.06-4.89; I2 = 0%).
CONCLUSIONS
AA is associated with an increase of SNHL, especially at high frequencies. Otologic consultation may be indicated if AA patients present with hearing loss or tinnitus.
Topics: Humans; Alopecia Areata; Cohort Studies; Cross-Sectional Studies; Hearing Loss, Sensorineural
PubMed: 37094565
DOI: 10.1159/000530784 -
Journal of the European Academy of... Apr 2023Recently, the impressive efficacy of JAK-inhibitors (JAK-I) in alopecia areata (AA) has been described in several studies; however, to date, there is limited information... (Review)
Review
Recently, the impressive efficacy of JAK-inhibitors (JAK-I) in alopecia areata (AA) has been described in several studies; however, to date, there is limited information on the safety of JAK-I in AA patients. For this reason, on 18 August 2022, a systematic review was performed to collect the premarketing and postmarketing data on the safety of JAK-I in patients treated for AA, evaluating for each molecule the reported adverse events (AEs) in indexed literature and their frequency. The keywords 'alopecia areata' AND 'Jak-inhibitors OR Janus-kinase Inhibitors' were searched on PubMed, Embase and Cochrane databases. Of 407 studies retrieved, 28 papers met the requirements and were used in our review, including five RCTs and 23 case series; overall, 1719 patients were included, and the safety of 6 JAK-I was assessed (baricitinib, brepocitinib, deuruxolitinib, ritlecitinib, ruxolitinib and tofacitinib). Systemic JAK-I were well-tolerated, most of the AEs were mild, and the withdrawal rate for AEs was very low and inferior to placebo in controlled studies (1.6% vs. 2.2%). Laboratory abnormalities represented 40.1% of AEs associated with oral JAK-I, which mostly included the rise in cholesterol, transaminase, triglycerides, creatine phosphokinase (CPK) and sporadic cases of neutro/lymphocytopenia. The remaining AEs involved the respiratory tract (20.8%), the skin (17.2%), the urogenital (3.8%), or the gastroenterological (3.4%) tract. Increased rates of infections involved not only the upper (19.0%) and lower (0.3%) respiratory tract, but also the urogenital system (3.6%) and the skin (4.6%). Isolated cases of grade 3 to 4 AEs have been reported, including myocardial infarction, hypertensive urgencies, cellulitis, rhabdomyolysis, neutropenia and high elevation of creatinine kinase. No fatal outcomes were reported. AEs reported with topical formulation included scalp irritation and folliculitis. The main limit of this review is the lack of data related to postmarketing surveillance, which should be maintained on a long-term basis.
PubMed: 37013725
DOI: 10.1111/jdv.19090 -
Drug Delivery and Translational Research Jun 2023Needle-free jet injectors are used for the intralesional treatment of various dermatological indications. However, a systematic review that evaluates the efficacy and... (Review)
Review
Needle-free jet injectors are used for the intralesional treatment of various dermatological indications. However, a systematic review that evaluates the efficacy and safety of these treatments has not been published. The objectives of this study are to evaluate the efficacy and safety of needle-free jet injections for dermatological indications and to provide evidence-based treatment recommendations. An electronic literature search was conducted in April 2022. Two reviewers independently selected studies based on predefined criteria and performed a methodological quality assessment using the Cochrane Collaborations risk-of-bias 2.0 assessment tool and Newcastle-Ottawa Scale. Thirty-seven articles were included, involving 1911 participants. Dermatological indications included scars, alopecia areata, hyperhidrosis, nail diseases, non-melanoma skin cancer, common warts, local anesthesia, and aesthetic indications. Keloids and other types of scars (hypertrophic, atrophic, and burn scars) were investigated most frequently (n = 7). The included studies reported favorable efficacy and safety outcomes for intralesional jet injector-assisted treatment with triamcinolone acetonide/hexacetonide, 5-fluorouracil, bleomycin, or hyaluronic acid. Two high-quality studies showed good efficacy and tolerability of intralesional jet injections with a combination of 5-fluorouracil and triamcinolone acetonide in hypertrophic scars and with saline in boxcar and rolling acne scars. No serious adverse reactions and good tolerability were reported in the included studies. Overall, the methodological quality of the included studies was low. Limited evidence suggests that needle-free jet injector-assisted intralesional treatment is efficacious and safe for hypertrophic and atrophic acne scars. More well-powered RCTs investigating the efficacy and safety of jet injector treatment in dermatology are warranted to make further evidence-based recommendations.
Topics: Humans; Triamcinolone Acetonide; Dermatology; Keloid; Fluorouracil; Acne Vulgaris; Treatment Outcome
PubMed: 36884194
DOI: 10.1007/s13346-023-01295-x -
Journal of Clinical Medicine Jan 2023Alopecia is associated with significant psychological burden. There is limited evidence on the use of psychological interventions in conditions of hair loss. This... (Review)
Review
Alopecia is associated with significant psychological burden. There is limited evidence on the use of psychological interventions in conditions of hair loss. This manuscript systematically reviews the current state of literature on psychological treatments for quality of life, mental health, and hair growth in various forms of alopecia. PubMed and Embase were searched with predefined inclusion and exclusion criteria. Reference lists were also examined for relevant studies. Nine articles met our criteria and are included in this review. Eight of the articles related to alopecia areata and one related to scarring alopecia. Mindfulness-based stress reduction (MBSR) was found to improve quality of life-related subjective symptoms, relationship impacts, anxiety, phobia, distress, and psychological symptom intensity. Alopecia-specific collocated behavioral health (CLBH) treatment showed a trend for psychosocial improvement in areas such as appearance shame, activity avoidance, negative emotions, and coping. Hypnotherapy was found to improve anxiety and depression, quality of life measures, and alexithymia. There was also some evidence for significant hair growth with hypnosis, but the data are mixed. Psychotherapy combined with immunotherapy led to more hair growth, and supported self-confidence. Finally, coping strategies modulated the subjective burden of alopecia, and were associated with disease improvement. Further research will be necessary to better establish the efficacy and optimal administration of these interventions in alopecia.
PubMed: 36769612
DOI: 10.3390/jcm12030964 -
JAMA Dermatology Mar 2023Two recent meta-analyses reported a high prevalence of both anxiety and depression in patients with alopecia areata (AA), as well as a positive association of AA with... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Two recent meta-analyses reported a high prevalence of both anxiety and depression in patients with alopecia areata (AA), as well as a positive association of AA with anxiety and depression, without distinguishing between disorders and symptoms. Yet, depression and anxiety can manifest either as symptoms identified in questionnaires or as specific diagnoses defined by Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision criteria.
OBJECTIVE
To perform a large meta-analysis separating the prevalence of depressive and anxiety disorders from that of depressive and anxiety symptoms in patients with AA.
DATA SOURCES
PubMed, ScienceDirect, the Cochrane Library, Embase, and PsycINFO databases were searched from inception through August 1, 2020.
STUDY SELECTION
Studies that contained data on the prevalence of depressive or anxiety disorders or symptoms were included.
DATA EXTRACTION AND SYNTHESIS
The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were used. Pooled prevalence was calculated with a random effects model meta-analysis that took into account between- and within-study variability. Meta-regressions were used to study the association between variations in prevalence and study characteristics.
MAIN OUTCOMES AND MEASURES
The prevalence of depressive and anxiety disorders and symptoms in patients with AA.
RESULTS
Thirty-seven articles (29 on depression and 26 on anxiety) that met the inclusion criteria were identified. By distinguishing between disorders and symptoms, the prevalence of both depressive disorders (9%) and unspecified anxiety disorders (13%) in patients with AA was shown to be greater than that in the general population. The prevalence and odds ratio (OR) of depressive disorders (prevalence, 9%; OR, 1.38) and anxiety disorders of which each category had been specifically studied (prevalence, 7%-17%; OR, 1.51-1.69) were markedly lower than that of depressive symptoms (prevalence, 37%; OR, 2.70) and anxiety symptoms (prevalence, 34%; OR, 3.07). Meta-regressions showed that variations in prevalence were mainly associated with methodological differences between studies.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, the separate analyses showed that 7% to 17% of patients with AA had depressive or anxiety disorders that require psychiatric care, including specific medication. Additionally, more than one-third of patients had symptoms that are warning signs and that need monitoring because they can develop into disorders.
Topics: Child; Humans; Alopecia Areata; Anxiety; Anxiety Disorders; Depression; Prevalence; Adult
PubMed: 36696123
DOI: 10.1001/jamadermatol.2022.6085 -
Acta Dermato-venereologica Jan 2023The aim of this study was to compare the efficacy and safety of treatment with Janus kinase inhibitors for alopecia areata, measured by change in Severity of Alopecia... (Meta-Analysis)
Meta-Analysis
The aim of this study was to compare the efficacy and safety of treatment with Janus kinase inhibitors for alopecia areata, measured by change in Severity of Alopecia Tool (SALT) score. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed using Medline, EMBASE and Cochrane library. All studies investigating the efficacy of treatments for alopecia areata were included. Primary outcomes were the proportion of patients with alopecia areata achieving 30%, 50%, 75%, 90% and 100% improvement in SALT score after treatment with a Janus kinase inhibitor. A meta-analysis was performed including all randomized controlled trials investigating Janus kinase inhibitors. A total of 37 studies matched the inclusion criteria and were included. Meta-analysis was performed based on 5 randomized studies. Regarding patients with alopecia areata defined as ≥ 50% scalp hair loss, baricitinib 4 mg once daily demonstrated the highest efficacy. However, among patients with alopecia areata defined as a SALT score ≥ 50, oral deuruxolitinib 12 mg twice daily demonstrated the highest efficacy. Deuruxolitinib and baricitinib appear to be promising drugs for the treatment of alopecia areata. However, the response depends on the dosage of the drug. More randomized trials, with identical inclusion criteria and dose and duration of treatment, are required to confirm these findings.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Alopecia; Pyrazoles
PubMed: 36695751
DOI: 10.2340/actadv.v103.4536 -
Annals of Medicine and Surgery (2012) Dec 2022Alopecia Areata (AA) is found to be the most prevalent autoimmune disorder amongst the general population. It was observed that AA patients are at a significantly higher... (Review)
Review
BACKGROUND
Alopecia Areata (AA) is found to be the most prevalent autoimmune disorder amongst the general population. It was observed that AA patients are at a significantly higher risk of developing obstructive sleep apnea and non-apneic insomnia than patients without AA. On the contrary, patients with identified sleep disorders were found to be more prone to developing AA as compared to the patients without sleep disorders. This study, therefore, validated the hypothesis of a bidirectional association between AA and sleep disorders.
AIMS
In this systematic review, our primary aim is to assess the prevalence of sleep disorders in Alopecia Areata patients while also assessing the inverse relationship between the two disorders.
METHODS
A literature search of MEDLINE, Google Scholar and Cochrane CENTRAL was performed from their inception to April 2022. Articles were selected for inclusion if they met the following eligibility criteria: (a) Studies enrolling patients having alopecia areata to assess the sleep quality. (b) Studies assessing the risks of alopecia areata in individuals with sleep disorder (c) Studies evaluating the bidirectional association between alopecia areata and sleep quality. Case reports, commentaries, and editorials were excluded. The outcomes of recruited studies were qualitatively synthesised and study findings are summarized in the results section and tabulated in summary tables.
RESULTS
Our search on electronic databases yielded 1562 articles. After abstract screening and full text review, 5 cross sectional and 3 cohort studies are included in this systematic review. Cases with PSQI scores higher than 5 and 6 were found to be in greater numbers amongst the AA patient population when compared to the control population ( < 0.001). Moreover, studies showed that patients with sleep disorders were greatly predisposed to develop subsequent AA as compared to patients without sleep disorders (aHR 4.70; 95% CI 3.99-5.54) (P < 0.0001).
CONCLUSION
The findings from our results display a significant bi-directional cause-effect relation between AA and sleep disorders. However, more large-scale observational studies on this subject are required to further validate our findings.
PubMed: 36582873
DOI: 10.1016/j.amsu.2022.104820