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Journal of the American Academy of... Sep 2023Characterization of upadacitinib use and switching from dupilumab to upadacitinib among patients with moderate-to-severe atopic dermatitis (AD) is needed. (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of switching from dupilumab to upadacitinib versus continuous upadacitinib in moderate-to-severe atopic dermatitis: Results from an open-label extension of the phase 3, randomized, controlled trial (Heads Up).
BACKGROUND
Characterization of upadacitinib use and switching from dupilumab to upadacitinib among patients with moderate-to-severe atopic dermatitis (AD) is needed.
OBJECTIVE
To evaluate the long-term safety and efficacy of continuous upadacitinib 30 mg and switching to upadacitinib after 24 weeks of dupilumab.
METHODS
Adults who completed the phase 3b clinical trial of oral upadacitinib 30 mg vs injectable dupilumab 300 mg (Heads Up) and entered a 52-week open-label extension (OLE) (NCT04195698) were included. All patients received 30-mg upadacitinib during the open-label period. We report results of a prespecified interim OLE 16-week analysis.
RESULTS
Patients (n = 239) continuing upadacitinib maintained high levels of skin and itch response. Patients (n = 245) switching from dupilumab experienced additional incremental improvements in clinical responses within 4 weeks of starting upadacitinib. Most patients who did not achieve adequate clinical responses with dupilumab did so with upadacitinib. The safety profile of upadacitinib up to 40 weeks (week 16 of OLE) was consistent with previous phase 3 AD studies, with no new safety risks observed.
LIMITATIONS
Open-label study design.
CONCLUSIONS
Clinical responses are maintained with continuous upadacitinib through 40 weeks and patients regardless of prior dupilumab response experienced improved outcomes when switched to upadacitinib. No new safety risks were observed.
Topics: Adult; Humans; Dermatitis, Atopic; Treatment Outcome; Double-Blind Method; Severity of Illness Index
PubMed: 37230366
DOI: 10.1016/j.jaad.2023.05.033 -
Nature Genetics Aug 2023Genome-wide association studies have identified many loci associated with hair and skin disease, but identification of causal variants requires deciphering of...
Genome-wide association studies have identified many loci associated with hair and skin disease, but identification of causal variants requires deciphering of gene-regulatory networks in relevant cell types. We generated matched single-cell chromatin profiles and transcriptomes from scalp tissue from healthy controls and patients with alopecia areata, identifying diverse cell types of the hair follicle niche. By interrogating these datasets at multiple levels of cellular resolution, we infer 50-100% more enhancer-gene links than previous approaches and show that aggregate enhancer accessibility for highly regulated genes predicts expression. We use these gene-regulatory maps to prioritize cell types, genes and causal variants implicated in the pathobiology of androgenetic alopecia (AGA), eczema and other complex traits. AGA genome-wide association studies signals are enriched in dermal papilla regulatory regions, supporting the role of these cells as drivers of AGA pathogenesis. Finally, we train machine learning models to nominate single-nucleotide polymorphisms that affect gene expression through disruption of transcription factor binding, predicting candidate functional single-nucleotide polymorphism for AGA and eczema.
Topics: Humans; Scalp; Chromatin; Genome-Wide Association Study; Transcriptome; Alopecia Areata; Hair Follicle; Eczema
PubMed: 37500727
DOI: 10.1038/s41588-023-01445-4 -
International Journal of Medical... 2024Hair loss, or alopecia, is a prevalent condition in modern society that imposes substantial mental and psychological burden on individuals. The types of hair loss,... (Review)
Review
Hair loss, or alopecia, is a prevalent condition in modern society that imposes substantial mental and psychological burden on individuals. The types of hair loss, include androgenetic alopecia, alopecia areata, and telogen effluvium; of them, androgenetic alopecia is the most common condition. Traditional treatment modalities mainly involve medical options, such as minoxidil, finasteride and surgical interventions, such as hair transplantation. However, these treatments still have many limitations. Therefore, exploring the pathogenesis of hair loss, specifically focusing on the development and regeneration of hair follicles (HFs), and developing new strategies for promoting hair regrowth are essential. Some emerging therapies for hair loss have gained prominence; these therapies include low-level laser therapy, micro needling, fractional radio frequency, platelet-rich plasma, and stem cell therapy. The aforementioned therapeutic strategies appear promising for hair loss management. In this review, we investigated the mechanisms underlying HF development and regeneration. For this, we studied the structure, development, cycle, and cellular function of HFs. In addition, we analyzed the symptoms, types, and causes of hair loss as well as its current conventional treatments. Our study provides an overview of the most effective regenerative medicine-based therapies for hair loss.
Topics: Humans; Hair Follicle; Hair; Finasteride; Alopecia Areata; Regeneration
PubMed: 38164355
DOI: 10.7150/ijms.88508 -
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 -
Indian Dermatology Online Journal 2023Alopecia areata (AA) is an immune-mediated condition, clinically manifesting as non-cicatricial patches of alopecia. It is often a self-limiting condition; however,... (Review)
Review
Alopecia areata (AA) is an immune-mediated condition, clinically manifesting as non-cicatricial patches of alopecia. It is often a self-limiting condition; however, regrowth of hair can take a long period of time, resulting in significant psychological comorbidity. With the recent advances in pathomechanisms of AA, the therapeutic approach to the condition has become more specific, and targeted therapy with small molecules is probably the ideal intervention. Many therapies exist for AA, but none of the systemic agents were approved, until recently, when baricitinib (Janus kinase (JAK1 and JAK2 inhibitor) gained FDA approval for the treatment of adult patients with severe AA. JAK inhibitors (JAKibs) target the γc cytokine and interferon-gamma (IFN-γ) signaling pathway, which is critical to the immunopathogenesis of AA and thus can reverse the hair loss in AA. Although JAKibs are emerging as a promising treatment modality for AA, the ideal JAKib is not yet settled, as there is scant data on H-2-H (head-to-head) comparisons of JAK inhibitors in AA. Moreover, the response achieved with JAKibs is not sustained after treatment discontinuation, with many studies showing a high recurrence rate with tofacitinib and ruxolitinib post-treatment. Also, recent studies have hypothesized that JAK2, with its ubiquitous expression, can cause adverse effects, unlike JAK1, which is associated with multiple major cytokine receptor families and JAK3, which is exclusively associated with the γc cytokine receptor. Thus, JAK3ibs may be associated with a better side effect profile and, in conjunction with their specificity, may replace other JAKibs as the treatment of choice for AA. We herein discuss the role of the JAK/STAT (signal transducer and activator of transcription) pathway in AA, the intricacies of various JAKibs in the management of AA, and emphasize the need for studies on tissue JAK and cytokine expression before arriving at the ideal JAKibs for AA.
PubMed: 37521227
DOI: 10.4103/idoj.idoj_452_22 -
Ugeskrift For Laeger Nov 2023Alopecia areata (AA) is an autoimmune disease where inflammation around the lowest part of the hair follicle results in non-scarring hair loss. This review investigates... (Review)
Review
Alopecia areata (AA) is an autoimmune disease where inflammation around the lowest part of the hair follicle results in non-scarring hair loss. This review investigates the course of the disease, its unpredictability and variation from a single patch of scalp hair loss to the loss of all hair on the body. The first drug with AA indication was approved in 2022, the JAK-inhibitor baricitinib. This paves the way for future research that may lead to the development of new effective pathogenesis-specific treatments.
Topics: Humans; Alopecia Areata; Alopecia; Autoimmune Diseases; Janus Kinase Inhibitors
PubMed: 38018739
DOI: No ID Found -
Proceedings of the National Academy of... Jul 2023Alopecia areata (AA) is among the most prevalent autoimmune diseases, but the development of innovative therapeutic strategies has lagged due to an incomplete...
Alopecia areata (AA) is among the most prevalent autoimmune diseases, but the development of innovative therapeutic strategies has lagged due to an incomplete understanding of the immunological underpinnings of disease. Here, we performed single-cell RNA sequencing (scRNAseq) of skin-infiltrating immune cells from the graft-induced C3H/HeJ mouse model of AA, coupled with antibody-based depletion to interrogate the functional role of specific cell types in AA in vivo. Since AA is predominantly T cell-mediated, we focused on dissecting lymphocyte function in AA. Both our scRNAseq and functional studies established CD8+ T cells as the primary disease-driving cell type in AA. Only the depletion of CD8+ T cells, but not CD4+ T cells, NK, B, or γδ T cells, was sufficient to prevent and reverse AA. Selective depletion of regulatory T cells (T) showed that T are protective against AA in C3H/HeJ mice, suggesting that failure of T-mediated immunosuppression is not a major disease mechanism in AA. Focused analyses of CD8+ T cells revealed five subsets, whose heterogeneity is defined by an "effectorness gradient" of interrelated transcriptional states that culminate in increased effector function and tissue residency. scRNAseq of human AA skin showed that CD8+ T cells in human AA follow a similar trajectory, underscoring that shared mechanisms drive disease in both murine and human AA. Our study represents a comprehensive, systematic interrogation of lymphocyte heterogeneity in AA and uncovers a novel framework for AA-associated CD8+ T cells with implications for the design of future therapeutics.
Topics: Mice; Humans; Animals; Alopecia Areata; Mice, Inbred C3H; Lymphocyte Subsets; Sequence Analysis, RNA
PubMed: 37428932
DOI: 10.1073/pnas.2305764120 -
Frontiers in Microbiology 2023Alopecia areata (AA) is a type of dermatological disease characterized by rapid and non-scarring hair loss of the scalp or body skin that may be related to genetic,... (Review)
Review
Alopecia areata (AA) is a type of dermatological disease characterized by rapid and non-scarring hair loss of the scalp or body skin that may be related to genetic, immunological and physiological factors. It is now believed that AA is associated with oxidative stress, autoimmune disease, neuropsychological factors, pathogens, immune checkpoint inhibitors and microecological imbalance under the premise of host genetic susceptibility. In recent years, studies have revealed the significant role of the gut microbiome or metabolome in many aspects of human health. Diverse studies have revealed that the gut microbiome and metabolome have an important influence on skin conditions. This review highlights the relationship between AA and the gut microbiome or metabolome to provide novel directions for the prevention, clinical diagnosis and treatment of AA.
PubMed: 38033589
DOI: 10.3389/fmicb.2023.1281660