Type 2 chronic inflammatory diseases: targets, therapies and unmet needs

Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(9), С. 743 - 767

Опубликована: Авг. 1, 2023

Язык: Английский

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Treatment of atopic dermatitis: Recently approved drugs and advanced clinical development programs

Allergy, Год журнала: 2024, Номер 79(6), С. 1501 - 1515

Опубликована: Янв. 8, 2024

Atopic dermatitis (AD) represents the most common skin disease characterized by heterogeneous endophenotypes and a high burden. In Europe, six new systemic therapies for AD have been approved: biologics dupilumab (anti-interleukin-4 receptor (IL-4R) α in 2017), tralokinumab (anti-IL-13 2021), lebrikizumab 2023), oral janus kinase (JAK) inhibitors (JAKi) targeting JAK1/2 (baricitinib 2020 EU) or JAK1 (upadacitinib 2021 abrocitinib 2022). Herein, we give an update on approvals, long-term safety, efficacy. Upadacitinib highest short-term efficacy among approved therapies. responders, catch up regarding incremental clinical benefit within continuous use. Recently, European Medicines Agency has released recommendations use of JAKi patients at risk (cardiovascular thromboembolic diseases, malignancies, (former) smoking, age ≥65 years). Furthermore, overview emerging currently Phase III trials. Among topical therapies, tapinarof (aryl hydrocarbon receptor), ruxolitinib (JAK1/2i), delgocitinib (pan-JAKi), asivatrep (anti-transient potential vanilloid), phosphodiesterase-4-inhibitors (roflumilast, difamilast) are discussed. current data cord-blood-derived mesenchymal stem cells, CM310 (anti IL-4Rα), nemolizumab (anti-IL-31RA), anti-OX40/OX40L-antibodies, neurokinin-receptor-1-antagonists, difelikefalin (κ-opioid-R) reported.

Язык: Английский

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OX40 in the Pathogenesis of Atopic Dermatitis—A New Therapeutic Target

American Journal of Clinical Dermatology, Год журнала: 2024, Номер 25(3), С. 447 - 461

Опубликована: Янв. 18, 2024

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified unpredictable flares, often have comorbidities secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay immune dysregulation barrier disruption drives pathogenesis, T-cell-dependent inflammation plays critical role patients AD. Despite new targeted therapies, many fail to achieve or sustain their individual treatment goals and/or may not be suitable for tolerate these therapies. There remains need novel, efficacious, well-tolerated therapeutic option deliver durable benefits across heterogeneous patient population. Expression OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], prominent T-cell co-stimulatory molecule, its ligand [OX40L; tumor (TNFSF4)] increased As pathway expansion, differentiation, survival effector memory T cells, targeting might promising approach provide sustained inhibition pathogenic cells associated broad control. Antibodies against [rocatinlimab (AMG 451/KHK4083) telazorlimab (GBR 830)] OX40L [amlitelimab (KY1005)] shown results early-phase studies AD, highlighting importance signaling as target

Язык: Английский

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Management of Patients Affected by Moderate-to-Severe Atopic Dermatitis with JAK Inhibitors in Real-World Clinical Practice: An Italian Delphi Consensus

Dermatology and Therapy, Год журнала: 2024, Номер 14(4), С. 919 - 932

Опубликована: Март 21, 2024

Several systemic therapies have been approved for the treatment of severe AD. In particular, Janus kinase inhibitors (JAKi), including abrocitinib, baricitinib, and upadacitinib, recently received approval patients with AD after being evaluated in several clinical trials. However, a few concerns raised regarding their long-term safety management these drugs real-world practice. this article we described results Delphi consensus aimed at describing knowledge on JAKi focusing, providing recommendations dermatologists daily practice use drugs. Twelve Italian reviewed most recent literature efficacy profiles proposed 24 statements. Agreement was reached statements focusing three main topics: (1) place therapy moderate-to-severe AD; (2) effectiveness JAK different phenotypes; (3) approaches to treated The panel all Given wide practice, it is crucial establish specific follow-up each patient's phenotype order achieve best possible outcome minimize potential adverse events.

Язык: Английский

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Overview of Atopic Dermatitis in Different Ethnic Groups

Journal of Clinical Medicine, Год журнала: 2023, Номер 12(7), С. 2701 - 2701

Опубликована: Апрель 4, 2023

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high prevalence worldwide, including countries from Asia, Africa, and Latin America, in different ethnic groups. In recent years, more attention has been placed on the heterogeneity of AD associated multiple factors, patient’s background, resulting an increasing body clinical, genetic, epidemiologic, immune-phenotypic evidence that delineates differences among racial Filaggrin (FLG) mutations, strongest genetic risk factor for development AD, are detected up to 50% European 27% Asian patients, but very rarely Africans. Th2 hyperactivation attribute all groups, though endotype also characterized by increased Th17-mediated signal, whereas African Americans show strong Th2/Th22 signature absence Th1/Th17 skewing. addition, may hold important therapeutic implications as predisposition affect treatment response and, thereby, tailored strategy better targets dominant immunologic pathways each subgroup be envisaged. Nevertheless, white patients represent largest ethnicity enrolled tested clinical trials most treated real-world setting, limiting investigations about safety efficacy across ethnicities. The purpose this review describe pathophysiology ethnicities its potential implications.

Язык: Английский

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Atopic dermatitis in children and adults

Deutsches Ärzteblatt international, Год журнала: 2023, Номер unknown

Опубликована: Март 22, 2023

Atopic dermatitis is a common, chronically recurring inflammatory skin disease. It gives rise to high disease burden and of major importance in social medicine.This review based on pertinent publications retrieved by selective search PubMed, including the current German European guidelines.Basic therapy with drug-free topical agents markedly improves barrier function skin. Adults should apply at least 250 g per week. Patient-specific trigger factors such as allergens, stress, microbial pathogens, or irritants be eliminated avoided. In mild moderately severe forms, external treatment glucocorticosteroids calcineurin inhibitors usually suffices; proactive given patients frequent recurrences long course Systemic anti-inflammatory biological dupilumab tralokinumab, Janus kinase baricitinib, upadacitinib, abrocitinib, conventional immunosuppressant drugs indicated particularly cases. The patient actively involved choice planning treatment; patient's age cutaneous findings taken into account. Interdisciplinary education yields sustained benefit.A combination baseline therapy, reactive systemic needed foundation successful interdisciplinary for atopic dermatitis.

Язык: Английский

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Is Atopic Dermatitis Only a Skin Disease?

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(1), С. 837 - 837

Опубликована: Янв. 3, 2023

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that imposes significant patient and population burdens. In addition to the cutaneous signs symptoms, growing evidence suggests AD systemic in nature. Certain diseases can possibly co-occur with as result of coincidental exposure similar environmental factors. However, it also suspected they are linked pathogenesis through more complex genetic immunological mechanisms, but these correlations remain less understood. It great need seek explanations for higher frequency number cardiovascular, autoimmune, neurological, psychiatric, metabolic disorders have been observed epidemiologic investigations among patients. Moreover, analysing immunology chronic inflammation its correction, activation, or suppression may prevent development variety comorbidities. As comorbid patients diagnosed potentially go undetected, physicians should be aware them.

Язык: Английский

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Treatment of severe atopic dermatitis with tralokinumab in clinical practice: short-term effectiveness and safety results

Clinical and Experimental Dermatology, Год журнала: 2023, Номер 48(9), С. 991 - 997

Опубликована: Апрель 25, 2023

Abstract Background Tralokinumab was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) and is first selective interleukin (IL)-13 inhibitor that specifically neutralizes IL-13 with high affinity. Objectives To determine real-life short-term effectiveness safety tralokinumab in patients AD. Methods A multicentre retrospective study conducted including adult AD who started from 1 April to 30 June 2022 16 Spanish hospitals. Demographic disease characteristics, severity quality life scales were collected at baseline visit weeks 4 16. Results Eighty-five included. Twenty-seven (32%) non-naive advanced therapy (biological or Janus kinase inhibitors inhibitors). All included had severe Eczema Area Severity Index (EASI) scores 25.4 (SD 8.1), Dermatology Life Quality (DLQI) 15.8 (5.4) peak pruritus numerical rating scale (PP-NRS) 8.1 (1.8) 65% an Investigator’s Global Assessment (IGA) 4. At week 16, there improvement on all scales. The mean EASI decreased 7.5 6.9, 70% improvement), SCORing Atopic Dermatitis improved 64% PP-NRS, 57%. Also, 82%, 58% 21% achieved 50, 75 90, respectively. percentage responders significantly higher among naive vs. groups (67% 41%). profile acceptable. Conclusions Patients, a long history prior multidrug failure, showed good response tralokinumab, confirming clinical trial results.

Язык: Английский

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Treatable Traits in Asthma: The Importance of Extrapulmonary Traits—GERD, CRSwNP, Atopic Dermatitis, and Depression/Anxiety

The Journal of Allergy and Clinical Immunology In Practice, Год журнала: 2024, Номер 12(4), С. 824 - 837

Опубликована: Янв. 24, 2024

Язык: Английский

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Dupilumab provides sustained effectiveness on patient-reported outcomes and favorable safety in patients with moderate-to-severe atopic dermatitis: Up to 5-year results from the daily practice BioDay registry

Journal of the American Academy of Dermatology, Год журнала: 2024, Номер 91(2), С. 300 - 311

Опубликована: Апрель 21, 2024

Background Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. Objective To evaluate outcome measures (PROMs) and the safety in patients with moderate-to-severe AD over a follow-up period up to 5 years. Methods Data were extracted from prospective, multicenter BioDay registry (October 2017 - 2022) treated practice. Results In total 1223 patients, 1108 adults 115 pediatric included. After ≥1 year treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8-8.7, 3.5-4.2, 2.9-3.1 adults, respectively, whilst these PROMs 8.9-10.9, 4.4-6.4, 3.0-3.7 respectively. At follow-up, overall work impairment decreased 40.1% 13.3-16.3% adults. Furthermore, class I obesity itch-dominant generally had less favorable treatment response. Of all 66.8% reported adverse event, conjunctivitis being most common(33.7%). Limitations The percentage missing values selected was 26% 46% patients. Conclusion addition safety, has demonstrated sustained effectiveness across various PROMs, underscoring patients' perspectives.

Язык: Английский

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