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Pharmacology & Therapeutics Nov 2017This review aims to address the mechanisms of compromised immune tolerance contributing to the development and maintenance of Alopecia Areata (AA). Our goal is to also... (Review)
Review
This review aims to address the mechanisms of compromised immune tolerance contributing to the development and maintenance of Alopecia Areata (AA). Our goal is to also highlight future treatment opportunities and therapeutics that will safely and efficiently restore hair growth and maintain patients in remission. AA is a presumptive autoimmune disorder that coincides and genetically clusters to several other autoimmune diseases. In this review, we pay attention to the learnings from the mechanistic research and drug development in these other autoimmune conditions. Interestingly, most of these diseases have been linked to compromised central and peripheral tolerance, and increased intestinal inflammation with enhanced gut permeability. Break of tolerance and priming of the autoreactive T-cells to attack antigenic epitopes in the hair follicle most likely requires several steps which include escape from negative selection and compromised peripheral tolerance. Local skin-related changes are also of importance due to the patchy manifestation of the skin areas with loss of hair, particularly in the early disease. Here, we discuss the defective mechanisms of tolerance, both central and peripheral, and hypothesize that the disease is driven by areas of tolerance break, and that these could be targeted for successful therapeutic interventions.
Topics: Alopecia Areata; Animals; Autoimmunity; Gastrointestinal Microbiome; Helminthiasis; Humans; Immune Tolerance
PubMed: 28546083
DOI: 10.1016/j.pharmthera.2017.05.008 -
Indian Journal of Dermatology,... 2023The Janus kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway has been identified as a key player in the pathophysiology of alopecia areata... (Review)
Review
The Janus kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway has been identified as a key player in the pathophysiology of alopecia areata and a potential target for therapy. Here, we give a narrative review of what is known about Janus kinase inhibitors in alopecia areata. Several clinical trials as well as smaller studies have demonstrated hair regrowth and remission with oral Janus kinase inhibitors therapy, even in patients who failed conventional treatment. Baricitinib is the only US FDA-approved treatment for alopecia areata but data for other oral Janus kinase inhibitors such as tofacitinib, ruxolitinib and ritlecitinib are also promising. Fewer clinical trials have investigated topical Janus kinase inhibitors for alopecia areata, with many of them terminated early due to unfavourable results. Overall, Janus kinase inhibitors are an efficacious addition to the therapeutic arsenal for treatment-refractory alopecia areata. Further work is needed to examine the effects of long-term usage of Janus kinase inhibitors, the efficacy of topical Janus kinase inhibitors, as well as to identify biomarkers that could predict differential therapeutic responses to the various Janus kinase inhibitors.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Alopecia; Hair; Janus Kinases
PubMed: 37436019
DOI: 10.25259/IJDVL_1093_2022 -
Acta Dermato-venereologica Nov 2023Several non-randomized clinical trials and retrospective studies have demonstrated encouraging efficacy and well-tolerated safety of tofacitinib in the treatment of... (Observational Study)
Observational Study
Several non-randomized clinical trials and retrospective studies have demonstrated encouraging efficacy and well-tolerated safety of tofacitinib in the treatment of alopecia areata. However, there are scarce data on a large cohort of patients with alopecia areata in long-term real-world practice. This single-centre, retrospective, observational cohort study included 126 patients with alopecia areata treated with tofacitinib between February 2021 and December 2022. The aims of this study are to evaluate drug survival, effectiveness and safety of tofacitinib for treatment of alopecia areata, and to identify potential factors influencing long-term outcomes. Median duration of treatment was 23.00 (interquartile range (IQR) 15.00, 47.25) weeks. Median all-cause survival time of 126 patients treated with tofacitinib was 44 weeks (95% confidence interval (95% CI) 36.3, 51.7), and the all-cause drug retention rate at 12 weeks, 24 weeks and 48 weeks were 90.0%, 66.4% and 42.3%, respectively. The most common reason for discontinuation was complete remission/satisfaction. A total of 80 patients treated with tofacitinib for over 6 months were included in the efficacy analysis, the overall complete response rate at 24 weeks was 33.8% (27/80). No life-threatening serious adverse events occurred. Sex is an independent risk factor in predicting patient outcomes. This real-world study confirmed the high effectiveness and acceptable safety profile of tofacitinib in alopecia areata, with a satisfactory drug survival rate, and provides supporting data for the clinical application of tofacitinib in Chinese patients with alopecia areata.
Topics: Humans; Alopecia Areata; Retrospective Studies; Protein Kinase Inhibitors; Pyrroles
PubMed: 37955531
DOI: 10.2340/actadv.v103.13475 -
Skin Therapy Letter May 2023Oral Janus kinase (JAK) inhibitors now have a position as first-line agents for treating advanced alopecia areata. Oral JAK inhibitors are considerably more effective... (Review)
Review
Oral Janus kinase (JAK) inhibitors now have a position as first-line agents for treating advanced alopecia areata. Oral JAK inhibitors are considerably more effective than topical JAK inhibitors, although topical agents may still have a valuable role for specific subgroups of patients. The US FDA approval of baricitinib in 2022 was an important milestone. Numerous JAK inhibitors are now being intensely studied for use in alopecia areata and several additional medications may also become approved in the near future. Accumulating clinical trial data points to a generally good safety profile for JAK inhibitors when used for patients with alopecia areata. However, long-term data pertaining to the safety and efficacy in this patient population are lacking.
Topics: Humans; Janus Kinase Inhibitors; Alopecia Areata
PubMed: 37339501
DOI: No ID Found -
American Family Physician Mar 2003Alopecia can be divided into disorders in which the hair follicle is normal but the cycling of hair growth is abnormal and disorders in which the hair follicle is... (Review)
Review
Alopecia can be divided into disorders in which the hair follicle is normal but the cycling of hair growth is abnormal and disorders in which the hair follicle is damaged. Androgenetic alopecia is the most common cause of hair loss in women. Other disorders include alopecia areata, telogen effluvium, cicatricial alopecia, and traumatic alopecias. The diagnosis is usually based on a thorough history and a focused physical examination. In some patients, selected laboratory tests or punch biopsy may be necessary. Topically administered minoxidil is labeled for the treatment of androgenetic alopecia in women. Corticosteroids and other agents are typically used in women with alopecia areata. Telogen effluvium is often a self-limited disorder. Because alopecia can be devastating to women, management should include an assessment for psychologic effects.
Topics: Administration, Topical; Alopecia Areata; Female; Glucocorticoids; Humans; Injections, Intralesional; Minoxidil; Triamcinolone Acetonide
PubMed: 12643360
DOI: No ID Found -
The Journal of Dermatological Treatment Dec 2023This analysis assessed association between scalp hair regrowth and improvements in health-related quality of life (HRQoL) and psychological burden in patients with...
Scalp hair regrowth is associated with improvements in health-related quality of life and psychological symptoms in patients with severe alopecia areata: results from two randomized controlled trials.
INTRODUCTION
This analysis assessed association between scalp hair regrowth and improvements in health-related quality of life (HRQoL) and psychological burden in patients with severe alopecia areata (AA).
METHODS
Data were pooled from two phase-3 trials ( = 1200). Patients randomized to once-daily placebo, baricitinib 2-mg, or 4-mg were analyzed independently of treatment allocation, and categorized according to scalp hair regrowth (at Week 36): meaningful regrowth (Severity of Alopecia Tool (SALT) score ≤20); intermediate regrowth (≥30% SALT improvement [SALT] at any post-baseline visit to Week 36, but SALT score > 20 at Week 36); no/minimal regrowth (never achieved SALT). Skindex-16 for AA score change-from-baseline and proportion of patients with baseline Hospital Anxiety and Depression Scale (HADS) scores ≥8 that shifted to <8 (normal) were assessed.
RESULTS
Patients with meaningful regrowth achieved greater improvements in all Skindex-16 AA domains versus no/minimal regrowth. More patients with meaningful versus no/minimal regrowth shifted from HADS ≥8 to <8 (anxiety:46.8% versus 26.4%; depression:52.3% versus 24.0%). Improvements occurred with intermediate regrowth but to a lesser extent versus meaningful regrowth.
CONCLUSIONS
Patients with severe AA and scalp hair regrowth at Week 36 experienced greater improvements in HRQoL and anxiety and depression versus patients with no/minimal regrowth. The highest benefit was observed in patients with meaningful regrowth (SALT score ≤20). NCT03570749 and NCT03899259.
Topics: Humans; Alopecia Areata; Scalp; Quality of Life; Randomized Controlled Trials as Topic; Hair
PubMed: 37381691
DOI: 10.1080/09546634.2023.2227299 -
Advances in Therapy Dec 2022Alopecia areata (AA), an autoimmune disease, is characterized by non-scarring hair loss involving the scalp, face, and/or body. Prior to 2022, no US Food and Drug...
INTRODUCTION
Alopecia areata (AA), an autoimmune disease, is characterized by non-scarring hair loss involving the scalp, face, and/or body. Prior to 2022, no US Food and Drug Administration (FDA)-approved treatments for AA were available in the USA; existing treatment options had limited efficacy and durability and are often associated with side effects. This study aimed to evaluate the current AA treatment patterns and treatment satisfaction as reported by dermatologists.
METHODS
Real-world data from a 2019 cross-sectional survey of US dermatologists and their adult patients with AA were analyzed. Dermatologists provided comprehensive data on their patients with AA, including AA dermatologist-assessed severity, treatments, treatment duration, treatment satisfaction, and reasons for dissatisfaction. The switching patterns among the proportion of patients on each of the treatment groups at the time of survey and, for those with prescription history, were reported.
RESULTS
A total of 442 patients with AA, treated by 90 dermatologists, were included in this analysis. At the time of survey, 45% of patients were being prescribed a combination of corticosteroids, 21% injectable corticosteroids, 11% topical corticosteroids/topical calcineurin inhibitor, and 10% immunomodulator as monotherapy or in combination. The majority (65%) of patients had no prior reported therapy. Among patients who were reported to have a prior therapy, frequent switching was to combination corticosteroids, injectable corticosteroids, and immunomodulators. Overall treatment dissatisfaction was high (24% dissatisfied and 29% neutral) and increased with AA severity.
CONCLUSIONS
This analysis provides a snapshot of the different local and systemic treatment options currently being used in a real-world treatment setting. Unfortunately, none of these treatments provide a sustainable, safe, and relapse-free solution, which leads to high treatment dissatisfaction rates and hence indicates a significant unmet need for the new and advanced treatment options for patients with AA.
Topics: Adult; Humans; United States; Alopecia Areata; Cross-Sectional Studies; Personal Satisfaction; Adrenal Cortex Hormones
PubMed: 36223027
DOI: 10.1007/s12325-022-02338-4 -
JAMA Dermatology Jul 2023Alopecia areata (AA) is associated with diverse autoimmune and psychiatric disorders. However, an investigation on the long-term outcomes for offspring born to mothers...
IMPORTANCE
Alopecia areata (AA) is associated with diverse autoimmune and psychiatric disorders. However, an investigation on the long-term outcomes for offspring born to mothers diagnosed with AA is lacking.
OBJECTIVE
To investigate the risks for autoimmune, inflammatory, atopic, thyroid, and psychiatric outcomes of offspring born to mothers with AA.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective population-based birth cohort study used the linked birth registration database with the Nationwide Health Insurance Service database of Korea. The participants included all newborns born to mothers with 3 or more visits with International Classification of Diseases, Tenth Revision code of L63 and 1:10 birth year, sex, insurance, income, and location of residence-matched control offspring born to mothers without AA during the years from 2003 to 2015. The analysis was conducted from July 2022 to January 2023.
EXPOSURE
Maternal AA.
MAIN OUTCOMES AND MEASURES
The occurrence of the following diseases was measured in newborns from birth to December 31, 2020: AA, alopecia totalis/universalis (AT/AU), vitiligo, psoriasis, inflammatory bowel disease, rheumatoid arthritis, atopic dermatitis, allergic rhinitis, asthma, hyperthyroidism, hypothyroidism, Graves disease, Hashimoto thyroiditis, attention-deficit hyperactivity disorder, mood disorder, and anxiety disorder. Multivariable Cox proportional hazard analyses were performed with the following covariates: birth year, age, insurance type, income level, location of residence, maternal age, mode of delivery, maternal history of atopic disorders, and autoimmune disorders.
RESULTS
In total, 67 364 offspring born to 46 352 mothers with AA and 673 640 controls born to 454 085 unaffected mothers were analyzed. The risk of AA (adjusted hazard ratio [aHR], 2.08; 95% CI, 1.88-2.30), AT/AU (aHR, 1.57; 95% CI, 1.18-2.08), vitiligo (aHR, 1.47; 95% CI, 1.32-1.63), atopic disorders (aHR, 1.07; 95% CI, 1.06-1.09), hypothyroidism (aHR, 1.14; 95% CI, 1.03-1.25), and psychiatric disorders (aHR, 1.15; 95% CI, 1.11-1.20) was significantly increased in offspring born to mothers with AA. Among them, 5088 born to mothers with AT/AU were at much greater risk for the development of AT/AU (aHR, 2.98; 95% CI, 1.48-6.00) and psychiatric disorders (aHR, 1.27; 95% CI, 1.12-1.44).
CONCLUSIONS AND RELEVANCE
In this Korean retrospective population-based birth cohort study, maternal AA was associated with the development of autoimmune/inflammatory, atopic, thyroid, and psychiatric disorders in their offspring. Clinicians and parents need to be aware of the potential for these comorbidities to occur.
Topics: Female; Humans; Infant, Newborn; Alopecia Areata; Mothers; Retrospective Studies; Cohort Studies; Vitiligo; Hypothyroidism
PubMed: 37223925
DOI: 10.1001/jamadermatol.2023.1261 -
British Medical Journal Feb 1979
Topics: Alopecia Areata; Autoantibodies; Dapsone; Dinitrochlorobenzene; Glucocorticoids; Humans
PubMed: 87235
DOI: No ID Found -
British Medical Journal Feb 1977
Topics: Alopecia Areata; Autoimmune Diseases; Humans
PubMed: 837086
DOI: No ID Found