Satisfaction with Control of Mild to Moderate Atopic Dermatitis with Ruxolitinib Cream: US Physician and Patient Perspectives.

INTRODUCTION: The 2021 US approval of ruxolitinib cream for treatment of atopic dermatitis (AD) in patients aged ≥ 12 years was based on the results of two pivotal phase 3 studies. Currently, real-world data to describe effectiveness of ruxolitinib cream and physician satisfaction with treatment remain limited. Our objective is to describe disease control among adults with mild to moderate AD prescribed ruxolitinib cream and physician satisfaction with treatment. METHODS: Data were from the Adelphi AD Disease Specific Programme™, a US real-world, cross-sectional survey of physician-reported data, undertaken between August 2022 and March 2023. For patients aged ≥ 18 years, physicians reported patient demographics, clinical characteristics, treatment patterns, and physician satisfaction with disease control. Descriptive analysis of data for patients with mild to moderate AD prior to the initiation of ruxolitinib cream and treated with ruxolitinib cream for ≥ 1 month was undertaken. RESULTS: Among physician-reported data from 1360 patients with AD, 149 patients had received ruxolitinib cream (in combination or as monotherapy) for ≥ 1 month, including 59 patients receiving monotherapy. Prior to treatment with ruxolitinib cream, 84.6% of patients had moderate AD (Investigator's Global Assessment, IGA of 3), whereas after treatment (median duration, 26 weeks), only 21.5% had an IGA of 3, with 48.3% of patients having clear or almost clear skin (IGA of 0/1). For these patients, 81.2% were not currently experiencing a flare, and physicians were satisfied with disease control for 87.3%. Results were similar in patients receiving monotherapy. The most frequent physician-reported reasons for prescribing ruxolitinib cream included relieving itch, improving lesion redness/thickness, achieving disease control, and reducing/controlling flares. CONCLUSIONS: These real-world findings demonstrate effective disease control and physician satisfaction with ruxolitinib cream for the treatment of AD in adults in a clinical practice setting. Outcomes were similar whether ruxolitinib cream was prescribed as monotherapy or in combination regimens, suggesting a role for ruxolitinib cream across the spectrum of disease.

Atopic dermatitis (AD) is a disease in which skin can be itchy, inflamed, and cracked. Traditional therapies for mild to moderate AD can be limited by side effects and long-term safety issues. After US approval of ruxolitinib cream for the treatment of mild to moderate AD in 2021, the goal of this study was to describe disease control and doctor satisfaction with ruxolitinib cream in a real-world setting. The Adelphi AD Disease Specific Programme™ surveyed 159 doctors who treated people with AD between August 2022 and March 2023. Doctors reported records from 1360 patients with mild to moderate AD. In these patients, ruxolitinib cream was used for at least 1 month in 149 patients and was used alone in 59 patients. Before the use of ruxolitinib cream, nearly 85% of the 149 patients had moderate AD. After the use of ruxolitinib cream, about 20% had moderate AD, with half having clear or almost clear skin. About 80% were not currently experiencing flares. Doctors were satisfied with disease control in more than 85% of patients. Patients applying ruxolitinib cream alone had similar results. Doctors most often prescribed ruxolitinib cream for itch relief, disease control, and to reduce or control flares. In summary, when ruxolitinib cream was used by patients, it provided good disease control, and doctors were satisfied with results. Outcomes were similar in patients who applied ruxolitinib cream alone or with another treatment. This suggests that ruxolitinib cream may be useful for patients with AD of differing levels of severity.

Ruxolitinib cream monotherapy demonstrates rapid improvement in the extent and signs of mild to moderate atopic dermatitis across head and neck and other anatomic regions in adolescents and adults: pooled results from 2 phase 3 studies.

Purpose: Ruxolitinib (selective Janus kinase [JAK] 1 and JAK2 inhibitor) cream demonstrated efficacy and safety in patients with atopic dermatitis (AD) in the phase 3 TRuE-AD studies. In TRuE-AD1/TRuE-AD2 (NCT03745638/NCT03745651), adults and adolescents with mild to moderate AD were randomized to apply twice-daily ruxolitinib cream or vehicle for eight weeks. Here, we evaluated the efficacy and tolerability of ruxolitinib cream by anatomic region, focusing on head/neck (HN) lesions that are typically difficult to manage and disproportionately affect quality of life (QoL).Materials and methods: Eczema Area and Severity Index (EASI) responses in anatomic regions were evaluated in the pooled population (N = 1208) and among patients with baseline HN involvement (n = 663). Itch, Investigator's Global Assessment (IGA), QoL, and application site tolerability were also assessed.Results: By Week 2 (earliest assessment), ruxolitinib cream application resulted in significant improvements across all EASI anatomic region subscores and AD signs versus vehicle, with further improvements through Week 8. Significantly more patients with HN involvement who applied ruxolitinib cream versus vehicle achieved clinically meaningful improvements in itch, IGA, and QoL. Application site reactions with ruxolitinib cream were infrequent (<3%), including in patients with HN involvement.Conclusions: These results support the use of ruxolitinib cream for AD treatment across all anatomic regions, including HN.

Clinically relevant improvements in adults and adolescents with atopic dermatitis who did not achieve Investigator's Global Assessment treatment success following 8 weeks of ruxolitinib cream monotherapy.

Ruxolitinib cream is a topical formulation of ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and JAK2. In two phase 3 studies in adults and adolescents (aged ≥12 years) with atopic dermatitis (AD; TRuE-AD1/TRuE-AD2), significantly more patients who applied ruxolitinib cream versus vehicle cream achieved Investigator's Global Assessment treatment success (IGA-TS; IGA score of 0/1 with ≥2-point improvement from baseline) at week 8 (primary endpoint). This post hoc analysis evaluated the efficacy, safety, and disease control of ruxolitinib cream in patients with AD who did not achieve IGA-TS at week 8. Patients in TRuE-AD1/TRuE-AD2 (N = 1249) were randomized 2:2:1 to apply twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 weeks followed by a long-term safety period in which patients applied ruxolitinib cream as needed. In this pooled analysis, clinically meaningful response thresholds included ≥50% improvement in the Eczema Area and Severity Index, ≥2-point reduction in the Itch Numerical Rating Scale, ≥4-point improvement in the Dermatology Life Quality Index (DLQI) or ≥6-point improvement in Children's DLQI, and ≥1-point reduction in IGA from baseline. Among patients who did not achieve IGA-TS at week 8 (n = 584), significantly more patients who applied either strength ruxolitinib cream versus vehicle achieved each response threshold at week 8. A response in ≥1 clinically meaningful endpoint was achieved in significantly more patients who applied ruxolitinib cream (93.4%/90.9% for 0.75%/1.5% ruxolitinib cream, respectively) versus vehicle (69.0%, both P < 0.0001). Progressive improvements in disease control were observed, with many patients achieving IGA-TS by week 52 (55.2%/56.3% for 0.75%/1.5% ruxolitinib cream, respectively). Ruxolitinib cream was well tolerated during the 52-week study in this patient population. Taken together, these results demonstrate that most patients with AD who did not achieve IGA-TS at week 8 have clinically meaningful responses to ruxolitinib cream, and continued therapy beyond 8 weeks could result in additional benefit.

Expression and subcellular localization of USH1C/harmonin in human retina provides insights into pathomechanisms and therapy.

Usher syndrome (USH) is the most common form of hereditary deaf-blindness in humans. USH is a complex genetic disorder, assigned to three clinical subtypes differing in onset, course and severity, with USH1 being the most severe. Rodent USH1 models do not reflect the ocular phenotype observed in human patients to date; hence, little is known about the pathophysiology of USH1 in the human eye. One of the USH1 genes, USH1C, exhibits extensive alternative splicing and encodes numerous harmonin protein isoforms that function as scaffolds for organizing the USH interactome. RNA-seq analysis of human retinae uncovered harmonin_a1 as the most abundant transcript of USH1C. Bulk RNA-seq analysis and immunoblotting showed abundant expression of harmonin in Müller glia cells (MGCs) and retinal neurons. Furthermore, harmonin was localized in the terminal endfeet and apical microvilli of MGCs, presynaptic region (pedicle) of cones and outer segments (OS) of rods as well as at adhesive junctions between MGCs and photoreceptor cells (PRCs) in the outer limiting membrane (OLM). Our data provide evidence for the interaction of harmonin with OLM molecules in PRCs and MGCs and rhodopsin in PRCs. Subcellular expression and colocalization of harmonin correlate with the clinical phenotype observed in USH1C patients. We also demonstrate that primary cilia defects in USH1C patient-derived fibroblasts could be reverted by the delivery of harmonin_a1 transcript isoform. Our studies thus provide novel insights into PRC cell biology, USH1C pathophysiology and development of gene therapy treatment(s).

Origami Microwave Imaging Array: Metasurface Tiles on a Shape-Morphing Surface for Reconfigurable Computational Imaging.

Origami is the art of paper folding that allows a single flat piece of paper to assume different 3D shapes depending on the fold patterns and the sequence of folding. Using the principles of origami along with computation imaging technique the authors demonstrate a versatile shape-morphing microwave imaging array with reconfigurable field-of-view and scene-adaptive imaging capability. Microwave/millimeter-wave based array imaging systems are expected to be the workhorse for sensory perception of future autonomous intelligent systems. The imaging capability of a planar array-based systems operating in complex scattering conditions have limited field-of-view and lack the ability to adaptively reconfigure resolution. To overcome this, here, deviations from planarity and isometry are allowed, and a shape-morphing computational imaging system is demonstrated. Implemented on a reconfigurable Waterbomb origami surface with 22 active metasurface panels that radiate near-orthogonal modes across 17-27 GHz, capability to image complex 3D objects in full details minimizing the effects of specular reflections in diffraction-limited sparse imaging with scene adaptability, reconfigurable cross-range resolution, and field-of-view is demonstrated. Such electromagnetic origami surfaces, through simultaneous surface shape-morphing ability (potentially with shape-shifting electronic materials) and electromagnetic field programmability, opens up new avenues for intelligent and robust sensing and imaging systems for a wide range of applications.

Psychosocial Effects of Vitiligo: A Systematic Literature Review.

BACKGROUND: Patients with vitiligo experience reduced quality of life. OBJECTIVE: To comprehensively describe the available evidence for psychosocial burden in vitiligo. METHODS: A systematic review of observational studies and clinical trials identified using PubMed, EMBASE, Scopus, and the Cochrane databases was performed through 1 March, 2021, to assess psychosocial comorbidities in vitiligo. Two independent reviewers performed an assessment of articles and extracted data for qualitative synthesis. RESULTS: Included studies (N = 168) were published between 1979 and 1 March, 2021; 72.6% were published since 2010. Disorders including or related to depression (41 studies, 0.1-62.3%) and anxiety (20 studies, 1.9-67.9%) were the most commonly reported. The most prevalent psychosocial comorbidities were feelings of stigmatization (eight studies, 17.3-100%), adjustment disorders (12 studies, 4-93.9%), sleep disturbance (seven studies, 4.6-89.0%), relationship difficulties including sexual dysfunction (ten studies, 2.0-81.8%), and avoidance or restriction behavior (12.5-76%). The prevalence of most psychosocial comorbidities was significantly higher vs healthy individuals. Factors associated with a significantly higher burden included female sex, visible or genital lesions, age < 30 years (particularly adolescents), and greater body surface area involvement, among others. The most commonly reported patient coping strategy was lesion concealment. LIMITATIONS: Available studies were heterogeneous and often had limited details; additionally, publication bias is possible. CONCLUSIONS: The results of this systematic review show that vitiligo greatly affects psychosocial well-being. The extent of psychosocial comorbidities supports the use of multidisciplinary treatment strategies and education to address the vitiligo-associated burden of disease. PROTOCOL REGISTRATION: PROSPERO (CRD42020162223).

Multiple sclerosis: a review of the disease and treatment options.

OBJECTIVE: To provide a review of the etiology, epidemiology, clinical features, diagnostic findings, and treatment options for multiple sclerosis (MS). DATA SOURCES: A PubMed search of English language articles using a combination of words: elderly; multiple sclerosis*, late onset multiple sclerosis*, etiology; screening; diagnosis; or treatment to identify original studies, guidelines, and reviews on multiple sclerosis and late-onset multiple sclerosis, published 2002 to 2013. Primary sources were then used to search for additional relevant material. STUDY SELECTION AND DATA EXTRACTION: Original studies, clinical reviews, references, and guidelines were obtained and evaluated for their clinical relevance. DATA SYNTHESIS: The literature included guidelines and considerations for the etiology, diagnosis, screening, and management of MS. CONCLUSION: MS is a chronic autoimmune disease characterized by inflammation, demyelination, and local axonal injury. It typically presents between ages 20 and 40 and largely affects women. However, 2% to 10% of individuals are diagnosed after 50 years of age. Diagnosis is based on presentation of clinical symptoms and the McDonald criteria for diagnosing MS. Management focuses on suppression of the immune system and prevention of relapses.