Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial

The Lancet, Год журнала: 2021, Номер 397(10290), С. 2169 - 2181

Опубликована: Май 21, 2021

Язык: Английский

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European guideline (EuroGuiDerm) on atopic eczema: part I – systemic therapy

Journal of the European Academy of Dermatology and Venereology, Год журнала: 2022, Номер 36(9), С. 1409 - 1431

Опубликована: Авг. 18, 2022

Abstract The evidence‐ and consensus‐based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline Consensus Statement Development Manual. Four consensus conferences were held between December 2020 July 2021. Twenty‐nine experts (including clinicians patient representatives) from 12 European countries participated. This first part of includes general information its scope purpose, health questions covered, target users a methods section. It also provides guidance which patients should be treated systemic therapies, as well recommendations detailed each drug. treatment options discussed comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab tralokinumab) janus kinase inhibitors (abrocitinib, baricitinib upadacitinib). Part two will address avoidance provocation factors, dietary interventions, immunotherapy, complementary medicine, educational occupational psychodermatological aspects, perspective considerations for paediatric, adolescent, pregnant breastfeeding patients.

Язык: Английский

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JAK inhibitors in the treatment of atopic dermatitis

Journal of Allergy and Clinical Immunology, Год журнала: 2021, Номер 148(4), С. 927 - 940

Опубликована: Авг. 24, 2021

Язык: Английский

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Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 19, 2023

Abstract The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism transmembrane transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, other specific molecules activate JAK-STAT signaling drive a series physiological pathological processes, including proliferation, metabolism, immune response, inflammation, malignancy. Dysregulated related genetic mutations are strongly associated activation cancer progression. Insights into structures functions have led development approval diverse drugs for clinical treatment diseases. Currently, been developed mainly target commonly divided three subtypes: cytokine or receptor antibodies, JAK inhibitors, STAT inhibitors. And novel agents also continue be tested in preclinical studies. effectiveness safety each kind drug warrant further scientific trials before put being applications. Here, we review current understanding fundamental composition function pathway. We discuss advancements JAK-STAT–related pathogenic mechanisms; targeted therapies various diseases, especially disorders, cancers; newly inhibitors; challenges directions field.

Язык: Английский

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JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Дек. 8, 2022

Atopic dermatitis (AD) is a chronic, inflammatory, pruritic form of dermatosis with heterogeneous manifestations that can substantially affect patients' quality life. AD has complex pathogenesis, making treatment challenging for dermatologists. The Janus kinase (JAK)–signal transducer and activator transcription (STAT) pathway plays central role in modulating multiple immune axes involved the immunopathogenesis AD. In particular, Th2 cytokines, including interleukin (IL)-4, IL-5, IL-13, IL-31, thymic stromal lymphopoietin, which contribute to symptoms chronic inflammation pruritus AD, are mediated by JAK–STAT signal transduction. Furthermore, regulation epidermal barrier modulation peripheral nerves related transduction pruritus. Targeting may attenuate these signals show clinical efficacy through suppression various pathways associated Topical oral JAK inhibitors variable selectivity have emerged as promising therapeutic options Notably, topical ruxolitinib, upadacitinib, abrocitinib were approved U.S. Food Drug Administration treating patients Accordingly, present study reviewed pathogenesis explored updated applications

Язык: Английский

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Innovation in the treatment of atopic dermatitis: Emerging topical and oral Janus kinase inhibitors

Allergology International, Год журнала: 2021, Номер 71(1), С. 40 - 46

Опубликована: Ноя. 21, 2021

Atopic dermatitis (AD) is characterized by chronic, eczematous, severe pruritic skin lesions. The knowledge on the pathogenesis of AD driving development new drugs. From research results, it has been revealed that Th2 cell-mediated immunity, barrier dysfunction, and pruritus cause a vicious cycle AD. On other hand, Janus kinase (JAK)/signal transducers activators transcription (STAT) pathway are one essential signaling pathways in various inflammatory diseases including In particular, TSLP, IL-4, IL-13 IL-22 occupy an important position for immune reaction. Moreover, experimentally pan-JAK inhibitor suppress STAT3 activation improved function. Furthermore IL-31 contribute lot to chronic AD, transmitted via JAK-STAT pathway. Therefore, JAK inhibitors promising candidates treatment Here we review clinical trials topical dergocitinib; inhibitor, ruxolitinib; JAK1 JAK2 tofacitinib; JAK1, JAK2, JAK3 oral baricitinib; abrocitinib upadacitinib; inhibitor. Significant improvements symptoms were obtained each drug with low frequency adverse events. have ability improve quickly. emergence these would be regarded as innovation atopic dermatitis.

Язык: Английский

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Systemic Immunomodulatory Treatments for Atopic Dermatitis

JAMA Dermatology, Год журнала: 2022, Номер 158(5), С. 523 - 523

Опубликована: Март 16, 2022

Importance

Systemic treatments for atopic dermatitis are being evaluated primarily in placebo-controlled trials; network meta-analysis can provide relative efficacy and safety estimates that have not been compared head to head.

Objective

To compare reported measures of assessments clinical trials systemic a living systematic review meta-analysis.

Data Sources

The Cochrane Central Register Controlled Trials, MEDLINE, Embase, Latin American Caribbean Health Science Information database, Global Resource EczemA Trials trial registries were searched through June 15, 2021.

Study Selection

Randomized examining 8 or more weeks treatment with immunomodulatory medications moderate-to-severe included after screening titles, abstracts, papers duplicate. Extraction Synthesis Data abstracted Bayesian meta-analyses assessed Grading Recommendations Assessment, Development Evaluation certainty evidence performed. updated analysis was completed from December

Main Outcomes Measures

include change Eczema Area Severity Index (EASI), Patient Oriented Measure (POEM), Dermatology Life Quality (DLQI), Peak Pruritus Numeric Rating Scales (PP-NRS).

Results

Since October 2019, 21 new studies added, total 60 16 579 patients. Up adults, abrocitinib, 200 mg daily (mean difference [MD], 2.2; 95% credible interval [CrI], 0.2-4.0; high certainty) upadacitinib, 30 (MD, 2.7; CrI, 0.6-4.7; associated reduced EASI slightly than dupilumab, 600 then 300 every 2 weeks. Abrocitinib, 100 −2.1; −4.1 −0.3; certainty), baricitinib, 4 −3.2; −5.7 −0.8; −5.2; −7.5 −2.9; tralokinumab, −3.5; −5.8 −1.3; less dupilumab. There little no between 15 daily, dupilumab 0.2; −1.9 certainty). pattern results similar POEM, DLQI, PP-NRS.

Conclusions Relevance

In this meta-analysis, mg; better scores mg, worse scores.

Язык: Английский

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Baricitinib in patients with moderate-to-severe atopic dermatitis: Results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5)

Journal of the American Academy of Dermatology, Год журнала: 2021, Номер 85(1), С. 62 - 70

Опубликована: Фев. 17, 2021

Язык: Английский

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Targeted Immunotherapy for Autoimmune Disease

Immune Network, Год журнала: 2022, Номер 22(1)

Опубликована: Янв. 1, 2022

In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, intracellular kinases have become standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, IL-23 has revolutionized treatment diseases, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis. B cell depletion therapy using anti-CD20 mAbs shown promising results in patients with neuroinflammatory inhibition survival factors is approved for systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells T also expected therapeutic potential diseases by modulating function. Recently, kinase JAK family, which responsible signal transduction from multiple receptors, garnered great interest field hematologic However, there are still unmet medical needs terms efficacy safety profiles. Emerging therapies aim induce tolerance without compromising function, advanced molecular engineering techniques.

Язык: Английский

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The translational revolution in atopic dermatitis: the paradigm shift from pathogenesis to treatment

Cellular and Molecular Immunology, Год журнала: 2023, Номер 20(5), С. 448 - 474

Опубликована: Март 16, 2023

Atopic dermatitis (AD) is the most common inflammatory skin disease, and it considered a complex heterogeneous condition. Different phenotypes of AD, defined according to patient age at onset, race, ethnic background; disease duration; other characteristics, have been recently described, underlying need for personalized treatment approach. Recent advancements in understanding AD pathogenesis resulted real translational revolution led exponential expansion therapeutic pipeline. The study biomarkers clinical studies emerging treatments helping clarify role each cytokine immune pathway will allow addressing unique fingerprints subset. Personalized medicine be ultimate goal this targeted research. In review, we discuss changes concepts both approach highlight scientific rationale behind report recent efficacy data.

Язык: Английский

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