Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma.
Klaus F. Rabe,Parameswaran Nair,Guy Brusselle,Jorge Maspero,Mario Castro,Lawrence Sher,Hongjie Zhu,Jennifer D. Hamilton,Brian N. Swanson,Asif Khan,Asif Khan,Jingdong Chao,Heribert Staudinger,Gianluca Pirozzi,Christian Antoni,Nikhil Amin,Marcella Ruddy,Bolanle Akinlade,Neil M.H. Graham,Neil Stahl,George D. Yancopoulos,Ariel Teper +21 more
TLDR
In patients with glucocorticoid‐dependent severe asthma, dupilumab treatment reduced oral glucoc Corticoid use while decreasing the rate of severe exacerbations and increasing the FEV1.Abstract:
Background Dupilumab is a fully human anti–interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. Its effectiveness in reducing oral glucocorticoid use in patients with severe asthma while maintaining asthma control is unknown. Methods We randomly assigned 210 patients with oral glucocorticoid–treated asthma to receive add-on dupilumab (at a dose of 300 mg) or placebo every 2 weeks for 24 weeks. After a glucocorticoid dose-adjustment period before randomization, glucocorticoid doses were adjusted in a downward trend from week 4 to week 20 and then maintained at a stable dose for 4 weeks. The primary end point was the percentage reduction in the glucocorticoid dose at week 24. Key secondary end points were the proportion of patients at week 24 with a reduction of at least 50% in the glucocorticoid dose and the proportion of patients with a reduction to a glucocorticoid dose of less than 5 mg per day. Severe exacerbation rates and the forced expira...read more
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Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma
Mario Castro,Jonathan Corren,Ian D. Pavord,Jorge Maspero,Sally E. Wenzel,Klaus F. Rabe,William W. Busse,Linda B. Ford,Lawrence Sher,J. Mark FitzGerald,Constance H. Katelaris,Yuji Tohda,Bingzhi Zhang,Heribert Staudinger,Gianluca Pirozzi,Nikhil Amin,Marcella Ruddy,Bolanle Akinlade,Asif Khan,Jingdong Chao,Renata Martincova,Neil M.H. Graham,Jennifer D. Hamilton,Brian N. Swanson,Neil Stahl,George D. Yancopoulos,Ariel Teper +26 more
TL;DR: Patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control.
Journal ArticleDOI
Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials
Claus Bachert,Claus Bachert,Joseph K. Han,Martin Desrosiers,Peter Hellings,Nikhil Amin,Stella E. Lee,Joaquim Mullol,Leon S. Greos,John V. Bosso,Tanya M. Laidlaw,Anders Cervin,Jorge Maspero,Claire Hopkins,Heidi Olze,G. Walter Canonica,Pierluigi Paggiaro,Seong H. Cho,Wytske Fokkens,Shigeharu Fujieda,M. Zhang,Xin Lu,Chunpeng Fan,Steven Draikiwicz,Siddhesh Kamat,Asif Khan,Gianluca Pirozzi,Naimish Patel,Neil M.H. Graham,Marcella Ruddy,Heribert Staudinger,David M. Weinreich,Neil Stahl,George D. Yancopoulos,Leda Mannent +34 more
TL;DR: Dupilumab significantly improved the coprimary endpoints in both studies and was added to standard of care in adults with severe CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both.
Journal ArticleDOI
The Cytokines of Asthma
TL;DR: The cytokine networks driving asthma are reviewed, placing these in cellular context and incorporating insights from cytokine-targeting therapies in the clinic, to argue that the development of new and improved therapeutics will require understanding the diverse mechanisms underlying the spectrum of asthma pathologies.
Journal ArticleDOI
Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis
Emma Guttman-Yassky,Emma Guttman-Yassky,Robert Bissonnette,Benjamin Ungar,Benjamin Ungar,Mayte Suárez-Fariñas,Marius Ardeleanu,Hitokazu Esaki,Maria Suprun,Yeriel Estrada,Hui Xu,Xiangyu Peng,Jonathan I. Silverberg,Alan Menter,James G. Krueger,Rick Zhang,Usman Chaudhry,Brian N. Swanson,Neil M.H. Graham,Gianluca Pirozzi,George D. Yancopoulos,Jennifer D. Hamilton +21 more
TL;DR: Dupilumab significantly improved clinical signs and symptoms of AD, was well tolerated, and progressively shifted the lesional transcriptome toward a nonlesional phenotype, as well as suppressing cellular/molecular cutaneous markers of inflammation and systemic measures of type 2 inflammation.
Journal ArticleDOI
Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline
Fernando Holguin,Juan Carlos Cardet,Kian Fan Chung,Sarah Diver,Diogenes S. Ferreira,Diogenes S. Ferreira,Anne M. Fitzpatrick,Mina Gaga,Liz Kellermeyer,Sandhya Khurana,Shandra L Knight,Vanessa M. McDonald,Rebecca L. Morgan,Victor E. Ortega,David Rigau,Padmaja Subbarao,Thomy Tonia,Ian M. Adcock,Eugene R. Bleecker,Christopher E. Brightling,Louis-Philippe Boulet,Michael D. Cabana,Mario Castro,Pascal Chanez,Adnan Custovic,Ratko Djukanovic,Urs Frey,Betty Frankemölle,Peter G. Gibson,Dominique Hamerlijnck,Nizar N. Jarjour,Satoshi Konno,Huahao Shen,Cathy Vitary,Andrew Bush +34 more
TL;DR: Clinical recommendations for the management of severe asthma are provided and the use of novel therapies for severe asthma, specifically biologicals for type 2 high asthma, and antimuscarinic agents and macrolides, as well as on biomarkers for predicting treatment response are made.
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Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma
Elisabeth H. Bel,Sally E. Wenzel,Philip J. Thompson,Charlene M. Prazma,Oliver N. Keene,Steven W. Yancey,Hector Ortega,Ian D. Pavord +7 more
TL;DR: In this paper, a randomized, double-blind trial involving 135 patients with severe eosinophilic asthma, compared the glucocorticoid-sparing effect of mepolizumab (at a dose of 100 mg) with that of placebo administered subcutaneously every 4 weeks for 20 weeks.
Journal ArticleDOI
Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma
Mario Castro,Jonathan Corren,Ian D. Pavord,Jorge Maspero,Sally E. Wenzel,Klaus F. Rabe,William W. Busse,Linda B. Ford,Lawrence Sher,J. Mark FitzGerald,Constance H. Katelaris,Yuji Tohda,Bingzhi Zhang,Heribert Staudinger,Gianluca Pirozzi,Nikhil Amin,Marcella Ruddy,Bolanle Akinlade,Asif Khan,Jingdong Chao,Renata Martincova,Neil M.H. Graham,Jennifer D. Hamilton,Brian N. Swanson,Neil Stahl,George D. Yancopoulos,Ariel Teper +26 more
TL;DR: Patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control.
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