Search

IntroductionAs new topical and systemic treatments become available for atopic dermatitis (AD), there is a need to understand how treatments are being used in routine clinical practice, their comparative effectiveness and their long-term safety in diverse clinical settings.Methods and analysisThe TARGET-DERM AD cohort is a longitudinal, observational study of patients with AD of all ages, designed to provide practical information on long-term effectiveness and safety unobtainable in traditional registration trials. Patients with physician-diagnosed AD receiving prescription treatment (topical or systemic) will be enrolled at academic and community clinical centres. Up to 3 years of retrospective medical records, 5 years of prospective medical records, and optional biological samples and patient-reported outcomes will be collected. The primary aims include characterisation of AD treatment regimens, evaluation of response to therapy, and description of adverse events.Ethics and disseminationTARGET-DERM has been approved by a central IRB (Copernicus Group IRB, 5000 Centregreen Way Suite 200, Cary, North Carolina 27513) as well as local and institutional IRBs. No additional Ethics Committee reviews. Results will be reviewed by a publications committee and submitted to peer-reviewed journals.Trial registration numberNCT03661866, pre-results.

This document provides information about a study on the effectiveness of ruxolitinib cream in treating vitiligo, a chronic autoimmune disease that causes depigmentation on the skin. The study found that repigmentation varied across different body regions, with the face, trunk, and proximal extremities showing better response than bony prominences, hands, and feet. Patients treated with ruxolitinib cream showed improvement in repigmentation over a 52-week period, with the head/neck and trunk responding the best. However, repigmentation of the hands and feet was more challenging. The study suggests that longer-term treatment and combination therapies may be helpful for achieving optimal repigmentation in difficult-to-treat areas. The document also provides information about the authors and their affiliations, as well as potential conflicts of interest. It includes a statement about data availability and an ethics statement regarding the trials conducted. [Extracted from the article]

It is well established that Ly6Chi monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6Chi monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6Chi monocytes consist of two distinct subpopulations (CXCR4hi and CXCR4lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4hi subset proliferates and is immobilized in the BM for the replenishment of functionally mature CXCR4lo monocytes. We propose that the CXCR4hi subset represents a transitional premonocyte population, and that this sequential step of maturation from cMoPs serves to maintain a stable pool of BM monocytes. Additionally, reduced CXCR4 expression on monocytes, upon their exit into the circulation, does not reflect its diminished role in monocyte biology. Specifically, CXCR4 regulates monocyte peripheral cellular activities by governing their circadian oscillations and pulmonary margination, which contributes toward lung injury and sepsis mortality. Together, our study demonstrates the multifaceted role of CXCR4 in defining BM monocyte heterogeneity and in regulating their function in peripheral tissues.

Toll-like receptors TLR7 and TLR9 are both implicated in the activation of autoreactive B cells and other cell types associated with systemic lupus erythematosus (SLE) pathogenesis. However, [Tlr9.sup.-/-] autoimmune-prone strains paradoxically develop more severe disease. We have now leveraged the negative regulatory role of TLR9 to develop an inducible rapid-onset murine model of systemic autoimmunity that depends on T cell detection of a membrane-bound OVA fusion protein expressed by MHC class [II.sup.+] cells, expression of TLR7, expression of the type I IFN receptor, and loss of expression of TLR9. These mice are distinguished by a high frequency of OVA-specific [Tbet.sup.+], [IFN-[gamma].sup.+], and FasL-expressing Th1 cells as well as autoantibody-producing B cells. Unexpectedly, contrary to what occurs in most models of SLE, they also developed skin lesions that are very similar to those of human cutaneous lupus erythematosus (CLE) as far as clinical appearance, histological changes, and gene expression. FasL was a key effector mechanism in the skin, as the transfer of FasL-deficient [DO11.sup.gld] T cells completely failed to elicit overt skin lesions. FasL was also upregulated in human CLE biopsies. Overall, our model provides a relevant system for exploring the pathophysiology of CLE as well as the negative regulatory role of TLR9., Introduction Cutaneous lupus erythematosus (CLE) refers to dermatologic features of systemic lupus erythematosus (SLE) that may or may not be associated with more systemic manifestations, such as arthritis, nephritis, or [...]

This article explores the advancements in targeted therapies for vitiligo, a skin condition that causes depigmentation. It emphasizes the importance of equity in drug development, particularly for individuals with skin of color who may experience more severe disfigurement. The US FDA has approved a topical JAK inhibitor called ruxolitinib as a treatment for vitiligo, but there is a lack of diversity in the study populations for these inhibitors. The article highlights the need for more inclusive clinical trials and discusses the racial disparities in these trials. It also suggests a multifaceted approach to address these disparities, including increasing awareness, improving access, and promoting diversity in clinical trial teams. [Extracted from the article]

Introduction/Background Vitiligo is a chronic autoimmune disease characterized by melanocyte destruction, leading to skin depigmentation. Limited data are available regarding the efficacy of long-term topical vitiligo treatment. In 2 randomized, double-blinded, vehicle-controlled phase 3 studies in adults and adolescents (aged ≥12 y) with nonsegmental vitiligo (TRuE-V1 [NCT04052425]; TRuE-V2 [NCT04057573]), ruxolitinib cream application resulted in statistically superior improvements in repigmentation versus vehicle in the primary and all key secondary endpoints at Week 24 and was well tolerated. In the open-label period of TRuE-V1/TRuE-V2 (Weeks 24-52) and the TRuE-V long-term extension (LTE; Weeks 52-104) study (NCT04530344), further improvements in facial and body repigmentation (as assessed by Vitiligo Area Scoring Index [VASI] responses) were observed through Week 104 among patients who continued to apply ruxolitinib cream. Objectives: In this pooled analysis, we evaluated shifts in facial and total body VASI (F-VASI/T-VASI) responses among patients with vitiligo who had limited or no repigmentation at Week 24 and who continued to apply ruxolitinib cream for an additional 80 weeks. Methods: In TRuE-V1/TRuE-V2, patients were randomized 2:1 to apply twice-daily 1.5% ruxolitinib cream or vehicle for 24 weeks, after which all patients could apply 1.5% ruxolitinib cream through Week 52. Patients who completed TRuE-V1/TRuE-V2 were eligible to enroll in the TRuE-V LTE. Patients who did not achieve ≥90% improvement in F-VASI at Week 52 continued to apply open-label 1.5% ruxolitinib cream until Week 104. Patients initially randomized to apply ruxolitinib cream who had <25% improvement from baseline in F-VASI or T-VASI at Week 24 and had non-missing VASI assessments at the evaluated time points were included in this analysis. Shifts in F-VASI and T-VASI were assessed among patients with no facial/body repigmentation or worsening depigmentation (≤0% improvement in F-VASI/T-VASI) and patients with limited facial/body repigmentation (>0%- <25% improvement in F-VASI/T-VASI) at Week 24. Results: Among patients with no facial repigmentation at Week 24, improvements in F-VASI at Weeks 52 and 104 were observed in 77.8% (49/63) and 97.1% (34/35) of patients, respectively. Among patients with limited facial repigmentation at Week 24, F-VASI improvements at Weeks 52 and 104 were observed in 64.0% (32/50) and 83.3% (30/36) of patients, respectively. Across both groups, 54.9% (39/71) of patients achieved =75% improvement from baseline in F-VASI (F-VASI75) at Week 104. Among those with no body repigmentation at Week 24, T-VASI improvements at Weeks 52 and 104 were observed in 79.6% (39/49) and 93.3% (28/30) of patients, respectively. For those with limited body repigmentation at Week 24, T-VASI improvements at Weeks 52 and 104 were observed in 64.5% (80/124) and 81.6% (62/76) of patients, respectively. Across both groups who had <25% improvement in total body repigmentation at Week 24, 50.0% (53/106) of patients achieved ≥50% improvement in T-VASI (T-VASI50) at Week 104. Conclusions: In the TRuE-V studies, ruxolitinib cream application for an additional 80 weeks resulted in improved repigmentation among patients with nonsegmental vitiligo who had limited or no repigmentation at Week 24. These 2-year TRuE-V results highlight the importance of prolonged treatment in patients with vitiligo, even when minimal or no repigmentation is achieved after 6 months of treatment. [ABSTRACT FROM AUTHOR]