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https://www.readbyqxmd.com/read/29036019/targeting-the-interleukin-4-and-interleukin-13-pathways-in-severe-asthma-current-knowledge-and-future-needs
#1
Amit D Parulekar, Christina C Kao, Zuzana Diamant, Nicola A Hanania
PURPOSE OF REVIEW: Severe asthma is a heterogeneous disease that can be classified into phenotypes and endotypes based upon clinical or biological characteristics. Interleukin (IL)-4 and IL-13 play a key role in type 2 (T2) asthma. This article reviews the signaling pathway of IL-4 and IL-13 and highlights its targeted therapy in severe asthma. RECENT FINDINGS: Several clinical trials of biologics targeting the IL-4/IL-13 pathway have recently been completed. In patients with severe, uncontrolled asthma, targeting IL-13 alone with biologics including lebrikizumab and tralokinumab has not shown consistent reduction in asthma exacerbations...
October 13, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29017221/-biologicals-in-the-treatment-of-bronchial-asthma
#2
I Haasler, C Taube
Biologicals are a therapeutic option for patients with severe asthma. Difficult asthma in patients with untreated comorbidities or persistent trigger factors is much more common than severe refractory asthma. Optimized medical treatment, adherence to medication, elimination of trigger factors and treatment of comorbidities are essential before escalating the therapy with a biological. A careful phenotyping of patient with severe asthma is necessary because all available biological are only effective in certain phenotypes of the disease...
October 2017: Pneumologie
https://www.readbyqxmd.com/read/28990423/dupilumab-for-the-treatment-of-asthma
#3
Corrado Pelaia, Alessandro Vatrella, Luca Gallelli, Rosa Terracciano, Paolo Navalesi, Rosario Maselli, Girolamo Pelaia
Dupilumab is a fully human IgG4 monoclonal antibody directed against the α subunit of the interleukin (IL)-4 receptor (IL-4Rα). Since the activation of IL-4Rα is utilized by both IL-4 and IL-13 to mediate their pathophysiological effects, dupilumab behaves as a dual antagonist of these two sister cytokines, which blocks IL-4/IL-13-dependent signal transduction. Areas covered: Herein, the authors review the cellular and molecular pathways activated by IL-4 and IL-13, which are relevant to asthma pathobiology...
October 8, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28987493/risk-of-infection-in-patients-with-atopic-dermatitis-treated-with-dupilumab-a-meta-analysis-of-randomized-controlled-trials
#4
Patrick Fleming, Aaron M Drucker
BACKGROUND: Atopic dermatitis (AD) is characterized by skin barrier defects, Th2 activation, and increased risk for cutaneous and extracutaneous infections. In clinical trials, dupilumab appeared to decrease rates of skin infections in AD. OBJECTIVE: We aimed to determine the impact of dupilumab on rates of skin and other infections in patients with moderate-to-severe AD. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of dupilumab for AD...
October 4, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28979129/dupilumab-in-the-management-of-moderate-to-severe-asthma-the-data-so-far
#5
REVIEW
Pilar Barranco, Elsa Phillips-Angles, Javier Dominguez-Ortega, Santiago Quirce
Severe asthma constitutes illness in a relatively small proportion of all patients with asthma, but it is a major public health problem - with considerable effect on morbidity, mortality, as well as a high burden on health care resources. Regardless of effective treatments being widely available and the existence of treatment guidelines, a large population of severe asthma cases remain uncontrolled. Achieving and maintaining asthma control in this group of patients is, therefore, of utmost importance. The recognition of distinct inflammatory phenotypes within this population has driven the development of targeted biological therapies - particularly, selective targeted monoclonal antibodies (mAbs)...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28971769/new-therapeutic-targets-and-drugs-for-the-treatment-of-asthma
#6
Mateus Feitosa Alves, Diogo Vilar da Fonsec, Sílvia Adelaide Linhares de Melo, Marcus Tullius Scotti, Luciana Scotti, Sócrates Golzio Dos Santos, Margareth de Fátima Formiga Melo Diniz
Asthma is an inflammatory disease which affects millions of people worldwide. Therefore, it is necessary search for new sources of therapies for the treatment of these patients in order to improve their quality of life. From content analysis of new therapeutic targets literature, there are various targets and drugs reported as promising for treatment asthma. Interleukins involved in inflammatory processes are often presented as candidate targets for new drugs. The action of such therapeutics would not only affect interleukins, but also in their receptors...
September 27, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28970084/expert-perspectives-on-management-of-moderate-to-severe-atopic-dermatitis-a-multidisciplinary-consensus-addressing-current-and-emerging-therapies
#7
REVIEW
Mark Boguniewicz, Andrew F Alexis, Lisa A Beck, Julie Block, Lawrence F Eichenfield, Luz Fonacier, Emma Guttman-Yassky, Amy S Paller, David Pariser, Jonathan I Silverberg, Mark Lebwohl
Atopic dermatitis (AD) is a common, chronic, relapsing, inflammatory skin disease that affects children and adults. Until recently, the only Food and Drug Administration-approved systemic treatment option for patients with moderate-to-severe AD was systemic steroids, which are not recommended by current guidelines and are commonly associated with disease rebound. Instead, clinicians choose from several off-label immunosuppressants, which can have serious adverse effects. A significant number of these patients go untreated...
September 29, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28948572/overlapping-effects-of-new-monoclonal-antibodies-for-severe-asthma
#8
REVIEW
Christian Domingo
Among the monoclonal antibodies (mAbs) developed for severe asthma treatment, three have already been marketed. Omalizumab was the first, more than 10 years ago; today, mepolizumab and reslizumab are also available in the European Union and the US. Omalizumab blocks free immunoglobulin E (IgE), mepolizumab and reslizumab block an interleukin (IL-5). In the near future, dupilumab and benralizumab are expected to emerge as two new alternatives. Benralizumab blocks the receptor for IL-5 (IL5-Rα) and has a direct cytotoxic effect on eosinophils, and dupilumab blocks the α-unit of the heterodimeric receptor for IL-4 and IL-13 (IL-4Rα); as a result, dupilumab can block both IL-4 and IL-13...
September 25, 2017: Drugs
https://www.readbyqxmd.com/read/28933010/economic-evaluation-of-dupilumab-for-the-treatment-of-moderate-to-severe-atopic-dermatitis-in-adults
#9
Andreas Kuznik, Gaëlle Bégo-Le-Bagousse, Laurent Eckert, Abhijit Gadkari, Eric Simpson, Christopher N Graham, LaStella Miles, Vera Mastey, Puneet Mahajan, Sean D Sullivan
INTRODUCTION: Dupilumab significantly improves signs and symptoms of atopic dermatitis (AD), including pruritus, symptoms of anxiety and depression, and health-related quality of life versus placebo in adults with moderate-to-severe AD. Since the cost-effectiveness of dupilumab has not been evaluated, the objective of this analysis was to estimate a value-based price range in which dupilumab would be considered cost-effective compared with supportive care (SC) for treatment of moderate-to-severe AD in an adult population...
September 20, 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/28919788/innovative-treatments-for-severe-refractory-asthma-how-to-choose-the-right-option-for-the-right-patient
#10
REVIEW
Francesco Menzella, Carla Galeone, Francesca Bertolini, Claudia Castagnetti, Nicola Facciolongo
The increasing understanding of the molecular biology and the etiopathogenetic mechanisms of asthma helps in identification of numerous phenotypes and endotypes, particularly for severe refractory asthma. For a decade, the only available biologic therapy that met the unmet needs of a specific group of patients with severe uncontrolled allergic asthma has been omalizumab. Recently, new biologic therapies with different mechanisms of action and targets have been approved for marketing, such as mepolizumab. Other promising drugs will be available in the coming years, such as reslizumab, benralizumab, dupilumab and lebrikizumab...
2017: Journal of Asthma and Allergy
https://www.readbyqxmd.com/read/28895959/atopic-dermatitis-emerging-therapies
#11
Eric Simpson, Jeremy Udkoff, Jenna Borok, Wynnis Tom, Lisa Beck, Lawrence F Eichenfield
Crisaborole and dupilumab represent the first 2 Food and Drug Administration (FDA)-approved therapies for atopic dermatitis (AD) in more than 15 years, and there are many promising drugs currently in development. This new wave of therapeutics capitalizes on the large body of work clarifying the pathogenesis of AD over the last several decades. In particular, type 2 cytokine-driven inflammation and skin barrier dysfunction are key processes underlying AD pathogenesis.
September 2017: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28887947/therapeutic-pipeline-for-atopic-dermatitis-end-of-the-drought
#12
REVIEW
Amy S Paller, Kenji Kabashima, Thomas Bieber
Until the past year, our therapeutic armamentarium for treating atopic dermatitis (AD) was still primarily topical corticosteroids and, for more severe disease, systemic immunosuppressants. The pipeline of more targeted topical and systemic therapies is expanding based on our growing understanding of the mechanism for AD and is particularly focused on suppressing the skewed immune activation. Most agents are in phase 2 clinical trials. Crisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor, became available in late 2016 in the United States for mild-to-moderate AD, with other PDE4 inhibitors, an agonist of the aryl hydrocarbon receptor, Janus kinase inhibitors, and commensal organisms also in trials for topical application...
September 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28882252/crisaborole-dupilumab-and-sarilumab
#13
Daniel A Hussar, Yunju Faith Lee
No abstract text is available yet for this article.
September 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28861617/novel-therapeutic-approaches-to-atopic-dermatitis
#14
REVIEW
Katarzyna Osinka, Karolina Dumycz, Bartłomiej Kwiek, Wojciech Feleszko
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. The number of people affected by AD is relatively high and seems to be rising. Although mild and moderate forms of the disease can be well controlled by the use of emollients, topical corticosteroids, and topical calcineurin inhibitors, treatment of severe is still a huge challenge. The new hope is biologic drugs, magic bullets in allergy, targeted at different points of the complex pathomechanism of inflammation in AD. In this review, novel biologic therapies are discussed, including recombinant monoclonal antibodies directed against various interleukin pathways (such as IL-4, IL-13, TSLP, IL-31, and IL-12/23), on immunoglobulin E, molecules acting as T cells, B cells, etc...
August 31, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28853956/new-and-emerging-targeted-systemic-therapies-a-new-era-for-atopic-dermatitis
#15
Dylan E Lee, Ashley K Clark, Khiem A Tran, Vivian Y Shi
PURPOSE: This is a review of emerging targeted, systemic therapies for atopic dermatitis (AD). The information presented aims to provide dermatologists with updated therapeutic options, stimulate academic interest, and spark future research. MATERIALS AND METHODS: Extensive search of ClinicalTrials.gov, the National Eczema Association, and PubMed was performed for clinical trials examining the effect of emerging targeted, systemic therapies in patients with AD. Results were included if they demonstrated efficacy in reversing AD symptoms...
August 30, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28845523/dupilumab-treatment-improves-quality-of-life-in-adult-patients-with-moderate-to-severe-atopic-dermatitis-results-from-a-randomized-placebo-controlled-clinical-trial
#16
A Tsianakas, T A Luger, A Radin
BACKGROUND: Dupilumab, a human anti-interleukin-4 receptor α monoclonal antibody, significantly improved clinical signs and symptoms in adults with moderate-to-severe atopic dermatitis (AD) in a randomized, double-blind, placebo-controlled, phase 2a trial. OBJECTIVES: We evaluate health-related quality of life (HRQoL) and correlation of HRQoL with secondary clinical and patient-reported outcomes in a subset of patients from this trial of dupilumab. METHODS: Patients were randomized to 300 mg weekly subcutaneous dupilumab or placebo for 12 weeks (NCT01548404)...
August 27, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28708993/il-4r%C3%AE-inhibitor-for-atopic-disease
#17
Howard Y Chang, Kari C Nadeau
Dupilumab is a fully human IgG4 monoclonal antibody directed against the IL-4Rα subunit of IL-4 and IL-13 receptors. It blocks the signaling pathways of IL-4 and IL-13, key cytokines that drive type 2 inflammatory response. In March 2017, dupilumab was approved for use in the treatment of atopic dermatitis (eczema). To view this Bench to Bedside, open or download the PDF.
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28674469/pharmaceutical-approval-update
#18
Mary Choy
Niraparib (Zejula) for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer; ocrelizumab (Ocrevus) for relapsing or primary progressive multiple sclerosis; and dupilumab (Dupixent) for moderate-to-severe atopic dermatitis.
July 2017: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/28668106/atopic-dermatitis-treatment-current-state-of-the-art-and-emerging-therapies
#19
Jonathan I Silverberg
BACKGROUND: Atopic dermatitis (AD) can be debilitating and often requires the use of combination topical and systemic therapy to achieve adequate disease control. METHODS: A non-systematic review was performed of current state of the art and emerging therapies for AD. RESULTS: There are a number of topical agents approved by the U.S. Food and Drug Administration (FDA) for the treatment of AD and multiple nonapproved systemic agents that are used off label for the treatment of AD...
July 1, 2017: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/28658541/the-interplay-between-genetic-and-environmental-factors-in-the-pathogenesis-of-atopic-dermatitis
#20
REVIEW
Atsushi Otsuka, Takashi Nomura, Pawinee Rerknimitr, Judith A Seidel, Tetsuya Honda, Kenji Kabashima
Atopic dermatitis (AD) is a chronic skin disorder characterized by pruritus and recurrent eczematous lesions that are accompanied by T-helper (Th)2-dominated inflammation. AD Etiology is not yet completely understood, but it is multifactorial. Moreover, the disease is characterized by complex interactions between genetic and environmental factors, such as skin barrier dysfunctions, allergy/immunity, and pruritus. For example, filaggrin is a key protein involved in skin barrier function. Th2 cells produce interleukin (IL)-31, which provokes pruritus, and other Th2 cytokines decrease filaggrin expression by keratinocytes...
July 2017: Immunological Reviews
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