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https://www.readbyqxmd.com/read/27906698/ige-and-eosinophils-as-therapeutic-targets-in-asthma
#1
Tanvi R Patel, Sanjiv Sur
PURPOSE OF REVIEW: Asthma is a chronic inflammatory disorder characterized by reversible airflow obstruction, which is being more widely recognized as a broad-spectrum disease that encompasses multiple patient characteristics and pathophysiologic mechanisms. Suboptimal asthma control leads to increasing burden of healthcare costs and loss of productivity to society. Biologic therapies targeted at IgE and eosinophils can be used in poorly controlled allergic and eosinophilic asthma, respectively...
November 30, 2016: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27778477/exploratory-population-pk-analysis-of-dupilumab-a-fully-human-monoclonal-antibody-against-il-4r%C3%AE-in-atopic-dermatitis-patients-and-normal-volunteers
#2
P Kovalenko, A T DiCioccio, J D Davis, M Li, M Ardeleanu, Nmh Graham, R Soltys
An exploratory population pharmacokinetic model for functional dupilumab was developed. Data from healthy volunteers and patients with atopic dermatitis (AD) receiving intravenous or subcutaneous doses were integrated. The data included 197 participants (2,518 measurements of dupilumab in serum) from six phase I and II studies. The data were analyzed using stochastic approximation expectation-maximization and importance sampling methods. The best structural model was a two-compartment model with parallel linear and Michaelis-Menten elimination from the central compartment...
October 25, 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27690741/two-phase-3-trials-of-dupilumab-versus-placebo-in-atopic-dermatitis
#3
Eric L Simpson, Thomas Bieber, Emma Guttman-Yassky, Lisa A Beck, Andrew Blauvelt, Michael J Cork, Jonathan I Silverberg, Mette Deleuran, Yoko Kataoka, Jean-Philippe Lacour, Külli Kingo, Margitta Worm, Yves Poulin, Andreas Wollenberg, Yuhwen Soo, Neil M H Graham, Gianluca Pirozzi, Bolanle Akinlade, Heribert Staudinger, Vera Mastey, Laurent Eckert, Abhijit Gadkari, Neil Stahl, George D Yancopoulos, Marius Ardeleanu
Background Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. Methods In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo...
September 30, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27637004/a-critical-evaluation-of-anti-il-13-and-anti-il-4-strategies-in-severe-asthma
#4
Diego Bagnasco, Matteo Ferrando, Gilda Varricchi, Giovanni Passalacqua, Giorgio Walter Canonica
Asthma is a high-prevalence disease, still accounting for mortality and high direct and indirect costs. It is now recognized that, despite the implementation of guidelines, a large proportion of cases remain not controlled. Certainly, adherence to therapy and the education of patients remain the primary objective, but the increasingly detailed knowledge about the pathogenic mechanisms and new biotechnologies offer the opportunity to better address and treat the disease. Interleukin (IL)-13 and IL-4 appear as the most suitable targets to treat the T helper 2 (TH2)-mediated forms (endotypes) of asthma...
2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27578076/itch-in-atopic-dermatitis-management
#5
Yayoi Kamata, Mitsutoshi Tominaga, Kenji Takamori
Patients with atopic dermatitis (AD) suffer from chronic inflammatory dermatitis and antihistamine-resistant itch. The management of intractable pruritus in AD is important, requiring the development of new therapeutic approaches. At present, the standard treatments for AD include topical anti-inflammatory drugs such as calcineurin inhibitors and corticosteroids. Topical emollient treatment is recommended to moisten the skin and to restore and maintain barrier function. Phototherapy is also effective in reducing the number of epidermal nerve fibers, normalizing imbalances in the levels of expression of axon guidance molecules, and inhibiting pruritus...
2016: Current Problems in Dermatology
https://www.readbyqxmd.com/read/27525671/assessing-the-new-and-emerging-treatments-for-atopic-dermatitis
#6
Lawrence F Eichenfield, Sheila F Friedlander, Eric L Simpson, Alan D Irvine
The newer and emerging treatments for atopic dermatitis (AD) focus on blockade of inflammatory cytokines, especially those that derive from T helper cell type 2 (TH2) and are associated with a pathway of immunoglobulin E (IgE) sensitization. Among the proinflammatory cytokines that have been identified as promising therapeutic targets are chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2), IgE, thymic stromal lymphopoietin (TSLP), and several monoclonal antibodies that block key cytokine pathways in the innate immune response...
June 2016: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/27497276/cellular-and-molecular-immunologic-mechanisms-in-patients-with-atopic-dermatitis
#7
REVIEW
Thomas Werfel, Jean-Pierre Allam, Tilo Biedermann, Kilian Eyerich, Stefanie Gilles, Emma Guttman-Yassky, Wolfram Hoetzenecker, Edward Knol, Hans-Uwe Simon, Andreas Wollenberg, Thomas Bieber, Roger Lauener, Peter Schmid-Grendelmeier, Claudia Traidl-Hoffmann, Cezmi A Akdis
Atopic dermatitis (AD) is a complex skin disease frequently associated with other diseases of the atopic diathesis. Recent evidence supports the concept that AD can also recognize other comorbidities, such as chronic inflammatory bowel or cardiovascular diseases. These comorbidities might result from chronic cutaneous inflammation or from a common, yet-to-be-defined immunologic background leading to immune deviations. The activation of immune cells and their migration to the skin play an essential role in the pathogenesis of AD...
August 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27453494/molecularly-targeted-therapies-for-asthma-current-development-challenges-and-potential-clinical-translation
#8
REVIEW
Ibrahim Sulaiman, Jonathan Chee Woei Lim, Hon Liong Soo, Johnson Stanslas
Extensive research into the therapeutics of asthma has yielded numerous effective interventions over the past few decades. However, adverse effects and ineffectiveness of most of these medications especially in the management of steroid resistant severe asthma necessitate the development of better medications. Numerous drug targets with inherent airway smooth muscle tone modulatory role have been identified for asthma therapy. This article reviews the latest understanding of underlying molecular aetiology of asthma towards design and development of better antiasthma drugs...
October 2016: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27334730/monoclonal-antibodies-for-the-management-of-severe-asthma
#9
Renata Rubinsztajn, Ryszarda Chazan
Asthma is a heterogeneous inflammatory disease. Most patients respond to current standard of care, i.e., bronchodilators, inhaled glucocorticosteroids and other anti-inflammatory drugs, but in some adequate asthma control cannot be achieved with standard treatments. These difficult-to-treat patients would be the target population for new biological therapies. At present, omalizumab is the only biological agent approved for the treatment of early-onset, severe IgE-dependent asthma. It is safe, effective, and well tolerated...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27268421/dupilumab-therapy-provides-clinically-meaningful-improvement-in-patient-reported-outcomes-pros-a-phase-iib-randomized-placebo-controlled-clinical-trial-in-adult-patients-with-moderate-to-severe-atopic-dermatitis-ad
#10
Eric L Simpson, Abhijit Gadkari, Margitta Worm, Weily Soong, Andrew Blauvelt, Laurent Eckert, Richard Wu, Marius Ardeleanu, Neil M H Graham, Gianluca Pirozzi, E Rand Sutherland, Vera Mastey
BACKGROUND: Moderate to severe atopic dermatitis (AD) is associated with substantial patient burden despite current therapies. OBJECTIVE: We sought to evaluate dupilumab treatment on patient-reported outcomes in adults with moderate to severe AD. METHODS: Adults (N = 380) with moderate to severe AD inadequately controlled by topical medications were randomized to 16 weeks of double-blind, subcutaneous treatment with dupilumab 100 mg every 4 weeks, 200 mg every 2 weeks, 300 mg every 2 weeks, 300 mg once weekly, or placebo...
September 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27258602/subcutaneous-dupilumab-and-mometasone-furoate-nasal-spray-for-chronic-rhinosinusitis-with-polyps
#11
John S Schneider
No abstract text is available yet for this article.
July 1, 2016: JAMA Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/27254629/-treatment-of-refractory-asthma-with-antibodies
#12
Marek Lommatzsch
Current guidelines of the global initiative for asthma (GINA) recommend the addition of biologics in step 5 of the stepwise asthma treatment approach. This review gives an overview on the effects and the clinical role of antibodies targeting immunoglobulin E, IgE (Omalizumab), Interleukin-5, IL-5 (Mepolizumab, Reslizumab) or the IL-5 receptor (Benralizumab). In addition, potential future treatment options of refractory asthma with antibodies (for instance Dupilumab) are discussed.
June 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27223113/dupilumab-a-monoclonal-antibody-for-atopic-dermatitis-a-review-of-current-literature
#13
K Blakely, M Gooderham, K Papp
Atopic dermatitis results when aberrant barrier function and immune activation occur within the skin. Standard therapies for atopic dermatitis have fallen short, prompting efforts to discover novel therapeutics for this disease. Of these, dupilumab, a fully human monoclonal antibody that inhibits the actions of both IL-4 and IL-13, has shown the greatest promise. Clinical trials of systemic dupilumab in moderate-to-severe atopic dermatitis have demonstrated marked improvement in patient symptoms, including pruritus and clinically visible disease...
March 2016: Skin Therapy Letter
https://www.readbyqxmd.com/read/27130691/dupilumab-efficacy-and-safety-in-adults-with-uncontrolled-persistent-asthma-despite-use-of-medium-to-high-dose-inhaled-corticosteroids-plus-a-long-acting-%C3%AE-2-agonist-a-randomised-double-blind-placebo-controlled-pivotal-phase-2b-dose-ranging-trial
#14
RANDOMIZED CONTROLLED TRIAL
Sally Wenzel, Mario Castro, Jonathan Corren, Jorge Maspero, Lin Wang, Bingzhi Zhang, Gianluca Pirozzi, E Rand Sutherland, Robert R Evans, Vijay N Joish, Laurent Eckert, Neil M H Graham, Neil Stahl, George D Yancopoulos, Mariana Louis-Tisserand, Ariel Teper
BACKGROUND: Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. Adults with uncontrolled persistent asthma who are receiving medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist require additional treatment options as add-on therapy. We aimed to assess the efficacy and safety of dupilumab as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist, irrespective of baseline eosinophil count...
July 2, 2016: Lancet
https://www.readbyqxmd.com/read/27130690/dupilumab-a-potential-new-treatment-for-severe-asthma
#15
COMMENT
Kian Fan Chung
No abstract text is available yet for this article.
July 2, 2016: Lancet
https://www.readbyqxmd.com/read/26967382/the-adaptive-immune-system-in-atopic-dermatitis-and-implications-on-therapy
#16
Lennart M Roesner, Thomas Werfel, Annice Heratizadeh
In atopic dermatitis (AD), the skin inflammation is believed to occur due to a misdirected immune reaction against harmless antigens on the one hand, and to a disturbed skin barrier on the other. In recent years, vast efforts have been made to investigate the relevance and details of the immune response to allergens. Clinically, it was demonstrated for the first time that aeroallergen exposure leads to worsening of AD symptoms. An overexpression of Th2 cytokines has been observed in acute and subacute lesions of AD...
July 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/26836729/effect-of-subcutaneous-dupilumab-on-nasal-polyp-burden-in-patients-with-chronic-sinusitis-and-nasal-polyposis-a-randomized-clinical-trial
#17
RANDOMIZED CONTROLLED TRIAL
Claus Bachert, Leda Mannent, Robert M Naclerio, Joaquim Mullol, Berrylin J Ferguson, Philippe Gevaert, Peter Hellings, Lixia Jiao, Lin Wang, Robert R Evans, Gianluca Pirozzi, Neil M Graham, Brian Swanson, Jennifer D Hamilton, Allen Radin, Namita A Gandhi, Neil Stahl, George D Yancopoulos, E Rand Sutherland
IMPORTANCE: Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases. OBJECTIVE: To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up...
February 2, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/26808004/target-oriented-therapy-emerging-drugs-for-atopic-dermatitis
#18
Felix Lauffer, Johannes Ring
INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a life-time prevalence of 10 - 20% in western countries. Patients suffer from stigmatizing eczematous skin lesions, persisting itch and sleep disorders. Starting usually in early childhood the course of AD is heterogeneous. While most frequently AD disappears before adolescence, about 30% of patients show a chronic persisting course. There is an urgent need for new therapeutic options as until now, specific drugs are missing...
2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/26800435/dupilumab-a-revolutionary-emerging-drug-in-atopic-dermatitis-and-its-possible-role-in-pemphigus
#19
Soheil Tavakolpour
No abstract text is available yet for this article.
September 2016: Dermatologic Therapy
https://www.readbyqxmd.com/read/26792414/-what-s-new-in-dermatological-therapy
#20
REVIEW
H Bachelez
During the ongoing year were published results from clinical trials opening new perspectives in the treatment of chronic inflammatory and dysimmune skin diseases. If this therapeutic development still predominantly on moderate-to- severe forms of plaque psoriasis, it tends to be more diversified towards moderate-to- severe forms of other diseases heavily impacting on patients'lives such as atopic dermatitis in adulthood, and hidradenitis suppurativa. Likewise, the development of IL-17 and IL-23 biological inhibitors, but also of small molecules such as tofacitinib in psoriasis, and the achievement of dupilumab phase 2 studies in atopic dermatitis provide evidence for the high efficacy of these therapies, while adalimumab is the first drug to be approved for the treatment of hidradenitis suppurativa...
December 2015: Annales de Dermatologie et de Vénéréologie
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