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Journal of Drugs in Dermatology : JDD Sep 2023Alopecia areata (AA) is a debilitating autoimmune disease that results in non-scarring hair loss. Baricitinib is the Food and Drug Administration (FDA) approved... (Review)
Review
BACKGROUND
Alopecia areata (AA) is a debilitating autoimmune disease that results in non-scarring hair loss. Baricitinib is the Food and Drug Administration (FDA) approved treatment for AA. Objective: Review the mechanism of action, pharmacokinetics, pharmacodynamics, efficacy, and safety of baricitinib in the treatment of AA. Methods: A literature review was conducted using the MEDLINE (PubMed) and EMBASE databases for articles published between January 2010 to November 2022. Articles in English discussing baricitinib's efficacy and safety in AA, pharmacodynamic, and pharmacokinetic profiles were included.
RESULTS
Two identical phase III trials (BRAVE-AA1 and BRAVE-AA2) were evaluated. A greater percentage of subjects receiving baricitinib 4 mg or 2 mg dose achieved a Severity of Alopecia Tool score equal to or less than 20 vs placebo. In BRAVE-AA1, for 4 mg, 2 mg, and placebo, respectively, these values were 38.8%, 22.8%, and 6.2%; in BRAVE-AA2, these values were 35.9%, 19.4%, and 3.3% (P<0.001).
DISCUSSION
Baricitinib is the first FDA-approved treatment for AA. Other treatments for AA are used off-label with variable efficacy. Baricitinib is associated with black-box warnings due to adverse effects (AEs) associated with other Janus Kinase (JAK) inhibitors or use in other diseases. In the two large AA trials, AEs were considered mild or moderate; those reported more often with baricitinib than placebo included acne, elevations of low- and high-density lipoprotein cholesterol, and elevation of creatinine kinase. Baricitinib is a relatively tolerable and safe therapeutic alternative for severe AA, although additional study is needed to assess its long-term efficacy and safety. Citation: Singh R, Driscoll MS. Review of baricitinib in the treatment of alopecia areata. J Drugs Dermatol. 2023;22(9):935-939. doi:10.36849/JDD.7357.
Topics: United States; Humans; Alopecia Areata; Azetidines; Purines; Janus Kinase Inhibitors
PubMed: 37683061
DOI: 10.36849/JDD.7357 -
Annales de Dermatologie Et de... Dec 2023Although non-scarring alopecia (NSA) is a frequent clinical finding in patients with systemic lupus erythematosus (SLE), it has been poorly described in the literature.... (Review)
Review
BACKGROUND
Although non-scarring alopecia (NSA) is a frequent clinical finding in patients with systemic lupus erythematosus (SLE), it has been poorly described in the literature. It is considered a nonspecific sign in the current classification of skin lesions of LE. The aim of this study was to give an updated overview of the spectrum of NSA in LE patients, with emphasis on the clinical significance thereof.
METHOD
We conducted a review of the English literature using the PubMed-Medline database using the keywords "Alopecia" + "Lupus erythematosus". Publications describing LE patients with NSA were included.
RESULTS
Data for 237 patients from 27 publications were analyzed. Ninety-one patients had diffuse NSA, 43 had patchy NSA, 83 had lupus hair, 3 had alopecia of dermal cutaneous LE, and 17 had alopecia of linear and annular lupus panniculitis of the scalp. Patients with diffuse/patchy NSA and lupus hair shared the following features: strong association with systemic activity of LE, subtle clinical/trichoscopic signs of inflammation, histological aspect consistent with lesions specific to cutaneous LE, high likelihood of response to SLE therapy, and absence of progression to scarring alopecia. Association with SLE was rare in patients with dermal cutaneous LE or linear and annular lupus panniculitis of the scalp, and skin-directed therapies were most often effective. One patient of each subtype progressed to scarring alopecia.
DISCUSSION
Diffuse/patchy NSA and lupus hair may represent a topographic variation of a single entity specific for LE. Prospective studies are warranted to further document the clinical significance of this manifestation.
Topics: Humans; Cicatrix; Panniculitis, Lupus Erythematosus; Alopecia; Skin Diseases; Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous
PubMed: 37598015
DOI: 10.1016/j.annder.2023.04.002 -
Journal of the American Academy of... Nov 2023Alopecia areata (AA) is a CD8+ T cell-mediated autoimmune disease characterized by nonscarring hair loss. Ivarmacitinib, which is a selective oral Janus kinase 1... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized, double-blind, placebo-controlled phase II study to evaluate the efficacy and safety of ivarmacitinib (SHR0302) in adult patients with moderate-to-severe alopecia areata.
BACKGROUND
Alopecia areata (AA) is a CD8+ T cell-mediated autoimmune disease characterized by nonscarring hair loss. Ivarmacitinib, which is a selective oral Janus kinase 1 inhibitor, may interrupt certain cytokine signaling implicated in the pathogenesis of AA.
OBJECTIVE
To evaluate the efficacy and safety of ivarmacitinib in adult patients with AA who have ≥25% scalp hair loss.
METHODS
Eligible patients were randomized 1:1:1:1 to receive ivarmacitinib 2, 4, or 8 mg once daily or placebo for 24 weeks. The primary end point was the percentage change from baseline in the Severity of Alopecia Tool score at week 24.
RESULTS
A total of 94 patients were randomized. At week 24, the least squares mean difference in the percentage change from baseline in the Severity of Alopecia Tool score for ivarmacitinib 2, 4, and 8 mg and placebo groups were -30.51% (90% CI, -45.25, -15.76), -56.11% (90% CI, -70.28, -41.95), -51.01% (90% CI, -65.20, -36.82), and -19.87% (90% CI, -33.99, -5.75), respectively. Two serious adverse events-follicular lymphoma and COVID-19 pneumonia-were reported.
LIMITATIONS
A small sample size limits the generalizability of the results.
CONCLUSION
Treatment with ivarmacitinib 4 and 8 mg doses in patients with moderate and severe AA for 24 weeks was efficacious and generally tolerated.
Topics: Humans; Adult; Alopecia Areata; COVID-19; Janus Kinase Inhibitors
PubMed: 37019385
DOI: 10.1016/j.jaad.2023.02.063 -
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 -
International Journal of Dermatology May 2024While observational studies have suggested a link between gut microbiota diversity and alopecia areata (AA), the causal relationship remains unclear.
BACKGROUND
While observational studies have suggested a link between gut microbiota diversity and alopecia areata (AA), the causal relationship remains unclear.
METHODS
We leveraged data from the MiBioGen and FinnGen consortiums' Genome-wide association studies (GWAS) encompassing gut microbiota (n = 13,266) and AA (n = 211,428) datasets. A comprehensive Mendelian randomization (MR) and reverse MR approach were employed, utilizing five statistical methods to evaluate causality. Sensitivity analyses were also conducted to corroborate the MR results.
RESULTS
Inverse variance weighted (IVW) analysis indicated a protective effect against AA from Butyricimonas (OR = 0.37, 95% CI: 0.18-0.77, P = 0.01), Enterorhabdus (OR = 0.40, 95% CI: 0.16-0.95, P = 0.04), Eubacterium (xylanophilum group) (OR = 0.36, 95% CI: 0.15-0.84, P = 0.02), and Phascolarctobacterium (OR = 0.37, 95% CI: 0.15-0.91, P = 0.03), while Ruminococcaceae UCG003 posed as a risk factor (OR = 2.79, 95% CI: 1.27-6.14, P = 0.01). Reverse MR showed no significant causal link between AA and gut microbiota, with no significant heterogeneity or horizontal pleiotropy.
CONCLUSIONS
Our analysis suggests probable causality between certain gut microbiota and AA, shedding light on its pathogenesis and potential intervention strategies.
Topics: Humans; Mendelian Randomization Analysis; Gastrointestinal Microbiome; Alopecia Areata; Genome-Wide Association Study; Risk Factors
PubMed: 38240406
DOI: 10.1111/ijd.17032 -
Skin Appendage Disorders Apr 2024Alopecia areata (AA) is an autoimmune condition that causes non-scarring hair loss on the scalp or other hair-bearing surfaces. Various signalling molecules regulate the... (Review)
Review
Alopecia areata (AA) is an autoimmune condition that causes non-scarring hair loss on the scalp or other hair-bearing surfaces. Various signalling molecules regulate the hair cycle and hair follicle regeneration. These include genes, growth factors, nuclear receptors, cytokines, and subcellular signalling pathways. Growth factors can cause the vascular endothelium and dermal fibroblasts to proliferate, extend the anagen phase, and delay the initiation of catagen in the hair follicle, thereby promoting hair growth. Microneedling causes the release of growth factors and has been shown to help high-molecular-weight drugs penetrate the stratum corneum and hair follicles. These recent discoveries regarding the pathogenesis of AA have resulted in the development of promising therapies. Herein, this article reviews the use of growth factors and microneedling in the treatment of AA and explores their efficacy and safety. Treatment with growth factors and microneedling appears to be highly effective for AA, with no major adverse effects, and may provide a new option for hair regeneration therapy. To support the efficacy of growth factors and microneedling for AA treatment, additional large-scale studies of patients with AA are needed.
PubMed: 38572186
DOI: 10.1159/000534636 -
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 -
Journal of Cosmetic Dermatology May 2024Alopecia areata (AA) is a recurrent immune-mediated disorder causing hair loss without any scarring being present. It affects hairs on the head or other parts of the... (Review)
Review
BACKGROUND
Alopecia areata (AA) is a recurrent immune-mediated disorder causing hair loss without any scarring being present. It affects hairs on the head or other parts of the body and can occur at any age and in both genders. It seems that AA is associated with a higher rate of psychological disorders resulting from hair loss and the esthetic and social repercussions of it. Common treatments like corticosteroids do not work for every patient and recent treatment options focusing on the immunologic mechanisms like tofacitinib have shown some promising results.
METHODS
It's a retrospective study on patients with AA, AT, AU taking oral tofacitinib as a treatment for at least 6 months. Scalp hair loss was assessed before treatment and at each visit using the Severity of Alopecia Tool (SALT) score.
RESULTS
Of 97 cases, 69.1% demonstrated over 50% SALT score improvement, with 44.3% having 90% or more decrease in SALT score. Patients who suffered from patchy AA were more responsive compared to patients with AT and AU subtypes and had a greater percent change in SALT score. Tofacitinib was tolerated quite well and no significant adverse events were reported.
CONCLUSIONS
Tofacitinib should be taken into consideration as an efficacious treatment option for patients with AA, AT and AU.
PubMed: 38736269
DOI: 10.1111/jocd.16356 -
Journal of Cosmetic Dermatology Sep 2023Janus kinase (JAK) inhibitors, biologics, and phosphodiesterase-4 (PDE-4) inhibitors are recent therapies for alopecia areata (AA)-albeit, knowledge gaps exist for these...
BACKGROUND
Janus kinase (JAK) inhibitors, biologics, and phosphodiesterase-4 (PDE-4) inhibitors are recent therapies for alopecia areata (AA)-albeit, knowledge gaps exist for these agents' relative efficacy.
OBJECTIVES
We determined the relative efficacy and safety of monotherapy with the aforementioned agents in adults with AA.
METHODS
The literature was systematically searched; we used data from randomized trials that investigated the agents' efficacy-as per Severity of Alopecia Tool (SALT) scores. Bayesian network meta-analyses were used to determine relative efficacy and safety. Effect modification was determined using a generalized linear model on aggregate data; evidence quality was evaluated.
RESULTS
Based on the surface under the cumulative ranking curve estimates obtained from multiple efficacy endpoints, regimens with the highest likelihood of achieving percent reduction in SALT scores, as well as a minimum 90%, 75% or 50% reduction in SALT scores are (in alphabetical order) baricitinib 4 mg once daily (QD), brepocitinib 60/30 mg QD, deuruxolitinib (CTP-543) 12 mg twice daily (BID), ritlecitinib 200/50 mg QD, ruxolitinib 20 mg BID and tofacitinib 5 mg BID. In contrast, dupilumab subcutaneous injections administered weekly and apremilast 30 mg BID were less likely to be effective. Discontinuation due to any adverse event was the least likely with oral JAK inhibitors, and more likely with dupilumab and apremilast.
CONCLUSIONS
Our results support the conduct of high-quality comparative trials to determine whether JAK inhibitors are more effective and safer than PDE4 inhibitors.
PubMed: 37452455
DOI: 10.1111/jocd.15903 -
Allergy, Asthma, and Clinical... Apr 2024Alopecia areata (AA), a prevalent form of autoimmune hair loss, has a not well-defined relationship with atopic and allergic disorders, including eczema, hay fever, and...
BACKGROUND
Alopecia areata (AA), a prevalent form of autoimmune hair loss, has a not well-defined relationship with atopic and allergic disorders, including eczema, hay fever, and asthma.
OBJECTIVES
This study aims to elucidate the genetic relationship between atopy, allergies, and alopecia areata (AA) using Mendelian randomization. We hypothesize that atopic and allergic conditions contribute to the genetic predisposition of AA.
METHODS
We analyzed extensive genetic data from Genome-wide Association Studies (GWAS) involving over one million individuals. This analysis focused on assessing the genetic correlation between AA and various allergic conditions, including hay fever, eczema, asthma, and allergies to pollen, dust, and cats. The inverse variance weighted method served as our primary analytical tool, complemented by sensitivity analyses to verify the robustness of our results.
RESULTS
Our findings reveal a significant genetic correlation between atopy/allergies and an increased risk of AA. Notably, strong associations were observed for hay fever, eczema, asthma, and specific allergies (pollen, dust, and cats). The sensitivity analyses corroborated these associations, reinforcing the reliability of our primary results.
CONCLUSIONS
This study provides compelling genetic evidence of an association between atopic and allergic conditions and the development of AA. These findings suggest that individuals with such conditions may benefit from enhanced surveillance for early signs of AA.
PubMed: 38678274
DOI: 10.1186/s13223-024-00892-w