Effectiveness and Safety of Upadacitinib in Combination with Topical Corticosteroids in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis DOI Creative Commons
Teppei Hagino,

Risa Hamada,

Mai Yoshida

et al.

Clinical Cosmetic and Investigational Dermatology, Journal Year: 2023, Volume and Issue: Volume 16, P. 3201 - 3212

Published: Nov. 1, 2023

To investigate the therapeutic effectiveness and safety of Janus kinase 1 inhibitor upadacitinib in adolescent patients with atopic dermatitis (AD).This study examined for 39 Japanese (aged 12-17 years) diagnosed moderate-to-severe AD from August 2021 to January 2023. The were treated 15 mg/day plus twice daily topical corticosteroids. Total eczema area severity index (EASI) or EASI on head neck, upper limbs, lower trunk erythema, edema/papulation, excoriation, lichenification, control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), laboratory indexes assessed at weeks 0, 4, 12 treatment. Treatment-emergent adverse events recorded.Total 4 anatomical sites rash types, ADCT, PP-NRS significantly reduced week compared 0. achievement rates 64.1% 62.5% 75, 93.5% 73.1% ADCT <7-point, 80.6% 60% ≥4-point improvement, respectively, indicating their slight decrease 12. percent reduction excoriation was higher than that lichenification edema/papulation 12, respectively. reductions erythema neck those limbs eosinophil counts (TEC) IgE 0 while TARC, IgE, TEC, LDH increased 4.These results suggest tolerability support its usefulness patients.

Language: Английский

The JAK/STAT signaling pathway: from bench to clinic DOI Creative Commons
Xiaoyi Hu, Jing Li,

Maorong Fu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 26, 2021

Abstract The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As fulcrum many vital cellular processes, the JAK/STAT constitutes rapid membrane-to-nucleus module induces expression various critical mediators cancer inflammation. Growing evidence suggests that dysregulation is associated with cancers autoimmune diseases. In this review, we discuss current knowledge about composition, activation, regulation pathway. Moreover, highlight role its inhibitors in

Language: Английский

Citations

1450
Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials DOI
Emma Guttman‐Yassky, Henrique D. Teixeira, Eric L. Simpson

et al.

The Lancet, Journal Year: 2021, Volume and Issue: 397(10290), P. 2151 - 2168

Published: May 21, 2021

Language: Английский

Citations

402
Cancer multidrug-resistance reversal by ABCB1 inhibition: A recent update DOI
Kritika Engle, Gautam Kumar

European Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 239, P. 114542 - 114542

Published: June 17, 2022

Language: Английский

Citations

117
Classification of human chronic inflammatory skin disease based on single-cell immune profiling DOI Open Access
Yale Liu, Hao Wang, Mark A. Taylor

et al.

Science Immunology, Journal Year: 2022, Volume and Issue: 7(70)

Published: April 15, 2022

Inflammatory conditions represent the largest class of chronic skin disease, but molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting complex mixture immune and stromal cell perturbations inflammatory disease states. We single-cell–profiled CD45 + transcriptomes from samples 31 patients (7 atopic dermatitis, 8 psoriasis vulgaris, 2 lichen planus (LP), 1 bullous pemphigoid (BP), 6 clinical/histopathologically indeterminate rashes, 7 healthy controls). Our data revealed active proliferative expansion T reg Trm components universal exhaustion human with a relative attenuation antigen-presenting cells. Skin-resident memory cells showed greatest transcriptional both dermatitis psoriasis, whereas also demonstrated recurrent abnormalities ILC CD8 cytotoxic lymphocytes. Transcript signatures differentiating these rash types included genes previously implicated helper (T H 2)/T 17 diatheses, segregated unbiased functional networks, accurately identified untrained validation sets. These gene were able to classify clinicopathologically ambiguous rashes diagnoses consistent therapeutic response. Thus, we have defined major classes at level described quantitative method instances pathologic inflammation. To make this approach accessible scientific community, created proof-of-principle web interface (RashX), where scientists clinicians can visualize their patient-level scRNA-seq–derived context our 2/T framework.

Language: Английский

Citations

98
Targeted Systemic Therapies for Adults with Atopic Dermatitis: Selecting from Biologics and JAK Inhibitors DOI
Richard W. Kim, Megan Lam, Katrina Abuabara

et al.

American Journal of Clinical Dermatology, Journal Year: 2024, Volume and Issue: 25(2), P. 179 - 193

Published: Jan. 12, 2024

Language: Английский

Citations

19
Colonization With Staphylococcus aureus in Atopic Dermatitis Patients: Attempts to Reveal the Unknown DOI Creative Commons

Patrycja Ogonowska,

Yolanda Gilaberte, Wioletta Barańska‐Rybak

et al.

Frontiers in Microbiology, Journal Year: 2021, Volume and Issue: 11

Published: Jan. 11, 2021

Atopic dermatitis (AD) patients are massively colonized with

Language: Английский

Citations

98
Abrocitinib: First Approval DOI Creative Commons

Emma D. Deeks,

Sean T. Duggan

Drugs, Journal Year: 2021, Volume and Issue: 81(18), P. 2149 - 2157

Published: Nov. 22, 2021

Abrocitinib (Cibinqo®) is an oral small-molecule inhibitor of Janus kinase 1 (JAK1) being developed by Pfizer for the treatment moderate-to-severe atopic dermatitis (AD). In September 2021, abrocitinib was approved in UK and Japan AD adults adolescents 12 years older who are candidates systemic therapy. has also received a positive CHMP opinion EU Regulatory applications drug have been submitted review to several other countries, including USA Australia. This article summarizes milestones development leading this first approval AD.

Language: Английский

Citations

88
Current Insights into Immunology and Novel Therapeutics of Atopic Dermatitis DOI Creative Commons

Hidaya A. Kader,

Muhammad Azeem,

Suhib A. Jwayed

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1392 - 1392

Published: June 4, 2021

Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to fifth population in developed countries. AD characterized by recurrent pruritic and localized eczema with seasonal fluctuations. initializes phenomenon atopic march, during which infant patients are predisposed progressive secondary allergies such as allergic rhinitis, asthma, food allergies. The pathophysiology complex; onset caused several factors, including strong genetic predisposition, disrupted epidermal barrier, immune dysregulation. was initially defects innate system a vigorous skewed adaptive Th2 response environmental agents; there compelling evidences that disorder involves multiple pathways. Symptomatic palliative treatment only strategy manage restore integrity. Researchers trying more precisely define contribution different genotypes elucidate role various axes. In this review, we have summarized current knowledge about roles responsive cells AD. addition, novel strategies for management comprehensively described, some ongoing clinical trials promising therapeutic agents. This information will provide an asset towards identifying personalized targets better outcomes.

Language: Английский

Citations

66
From Emollients to Biologicals: Targeting Atopic Dermatitis DOI Open Access
Lorenzo Salvati, Lorenzo Cosmi, Francesco Annunziato

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(19), P. 10381 - 10381

Published: Sept. 26, 2021

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and significantly impacts patients’ lives, particularly in its severe forms. AD clinical presentation varies over course of disease, throughout different age groups, across ethnicities. characterized by a spectrum phenotypes as well endotypes. Starting from current description pathogenesis, this review explores rationale approved therapies emollients to biologicals introduces novel promising drugs.

Language: Английский

Citations

56
Atopic dermatitis: pathomechanisms and lessons learned from novel systemic therapeutic options DOI Creative Commons
Thomas Bieber, Amy S. Paller, Kenji Kabashima

et al.

Journal of the European Academy of Dermatology and Venereology, Journal Year: 2022, Volume and Issue: 36(9), P. 1432 - 1449

Published: May 16, 2022

Atopic dermatitis (AD) is a chronic, heterogenous, inflammatory skin disorder associated with high skin-related health burden, typically starting in childhood and often persisting into adulthood. AD characterized by wide range of clinical phenotypes, reflecting multiple underlying pathophysiological mechanisms interactions between genetics, immune system dysregulation environmental factors. In this review, we describe the diverse cellular molecular involved AD, including critical role T-cell-driven inflammation, primarily via T helper (Th) 2- Th17-derived cytokines, many which are mediated Janus kinase (JAK) signaling pathway. These local processes interact sensory neuronal pathways, contributing to manifestations itch, pain sleep disturbance. The recent elucidation pathways has allowed treatment strategies evolve from broad-acting systemic immunosuppressive therapies more targeted agents, JAK inhibitors cytokine-specific biologic agents. Evidence development these reinforced expanded our understanding holds promise for individualized tailored specific subtypes.

Language: Английский

Citations

55