Read by QxMD icon Read


Elisabeth H Bel, Anneke Ten Brinke
Asthma and COPD are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and they are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade, several monoclonal antibodies and small molecule therapies have been developed to target this trait...
June 2, 2017: Chest
Tracy L Staton, Joseph R Arron, Julie Olsson, Cécile T J Holweg, John G Matthews, David F Choy
No abstract text is available yet for this article.
May 2017: Journal of Allergy and Clinical Immunology
T Karelina, V Voronova, O Demin, G Colice, B M Agoram
Emerging T-helper type 2 (Th2 ) cytokine-based asthma therapies, such as tralokinumab, lebrikizumab (anti-interleukin (IL)-13), and mepolizumab (anti-IL-5), have shown differences in their blood eosinophil (EOS) response. To better understand these effects, we developed a mathematical model of EOS dynamics. For the anti-IL-13 therapies, lebrikizumab and tralokinumab, the model predicted an increase of 30% and 10% in total and activated EOS in the blood, respectively, and a decrease in the total and activated EOS in the airways...
November 2016: CPT: Pharmacometrics & Systems Pharmacology
Saloumeh Kadkhodayan Fischer, Melissa Cheu, Kun Peng, John Lowe, James Araujo, Elaine Murray, Dana McClintock, John Matthews, Patricia Siguenza, An Song
Host cell proteins are manufacturing process-related impurities that may co-purify with the product despite extensive efforts to optimize the purification process. The risks associated with these impurities can vary and may be patient and/or therapeutic dependent. Therefore, it is critical to monitor and control the levels of these impurities in products and their potential impact on safety and efficacy. Lebrikizumab is a humanized immunoglobulin G4 monoclonal antibody (mAb) that binds specifically to soluble interleukin 13...
January 2017: AAPS Journal
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
Nicola A Hanania, Phillip Korenblat, Kenneth R Chapman, Eric D Bateman, Petr Kopecky, Pierluigi Paggiaro, Akihito Yokoyama, Julie Olsson, Sarah Gray, Cecile T J Holweg, Mark Eisner, Charles Asare, Saloumeh K Fischer, Kun Peng, Wendy S Putnam, John G Matthews
BACKGROUND: In phase 2 trials, lebrikizumab, an anti-interleukin-13 monoclonal antibody, reduced exacerbation rates and improved FEV1 in patients with uncontrolled asthma, particularly in those with high concentrations of type 2 biomarkers (eg, periostin or blood eosinophils). We undertook replicate phase 3 studies to assess the efficacy and safety of lebrikizumab in patients with uncontrolled asthma despite inhaled corticosteroids and at least one second controller medication. METHODS: Adult patients with uncontrolled asthma, pre-bronchodilator FEV1 40-80% predicted, and stable background therapy were randomly assigned (1:1:1) with an interactive voice-web-based response system to receive lebrikizumab 37·5 mg or 125 mg, or placebo subcutaneously, once every 4 weeks...
October 2016: Lancet Respiratory Medicine
Kenji Izuhara, Shoichiro Ohta, Junya Ono
Periostin acts both as an extracellular matrix protein belonging to the fasciclin family and as a matricellular protein functioning in cell activation by binding to its receptors on the cell surface. It has been established that periostin is a downstream molecule of interleukin (IL)-13, a signature type 2 cytokine, and that periostin plays an important role in the pathogenesis of allergic diseases, including asthma. Based on these findings, much attention has been paid to periostin as a biomarker useful in the treatment of asthma...
November 2016: Allergy, Asthma & Immunology Research
Sabina Antonela Antoniu
INTRODUCTION: In asthma, most commonly, 'conventional' anti-inflammatory medications represented by inhaled corticosteroids and leukotriene inhibitors are effective. In some patients however additional inhibition of the airways inflammation is necessary. Such compounds might be molecules inhibiting specifically certain inflammation pathways and lebrikizumab an anti IL-13 molecule might represent a relevant example as a potential asthma therapy. AREAS COVERED: Discussion of the rationale for the use of lebrikizumab in asthma...
October 2016: Expert Opinion on Investigational Drugs
Isao Suzaki, Shuichi Kawano, Kosaku Komiya, Tsuyoshi Tanabe, Tomohiro Akaba, Kazuhito Asano, Harumi Suzaki, Kenji Izuhara, Bruce K Rubin
BACKGROUND AND OBJECTIVE: Serum periostin is increased in asthma and serves as a surrogate marker for IL-13 activity in the lung. Serum levels of periostin are the most robust biomarker predicting a favourable response to the anti-IL-13 drug, lebrikizumab. We investigated the mechanisms of IL-13 stimulation of periostin, the polarized secretion of periostin and whether periostin would have a direct effect on mucin secretion by airway cells. METHODS: Normal human bronchial epithelial (NHBE) cells were cultured at air-liquid interface (ALI) in the presence of IL-13, and we evaluated the effect of the specific inhibitors, leflunomide (Janus kinase (JAK)/signal transducer and activator of transcription factor 6 (STAT6) inhibitor) or PD98059 (MEK/extracellular regulated protein kinase (ERK) inhibitor), on periostin production...
January 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
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
Stephen Bujarski, Amit D Parulekar, Nicola A Hanania
Severe asthma continues to be a major clinical problem despite the availability of effective asthma medications such as inhaled corticosteroids. Several targeted biologic therapies are emerging to treat patients with severe asthma. Areas Covered: This review provides an update of information on lebrikizumab, a novel monoclonal antibody that targets IL-13 and is currently in advanced stages of development. It describes the role of IL-13, a key effector cytokine in Type 2 (T2) airway inflammation in asthma and discusses the results of recent phase 2 trials investigating lebrikizumab's efficacy and safety in patients with severe asthma...
May 10, 2016: Expert Opinion on Biological Therapy
Kenji Izuhara, Simon J Conway, Bethany B Moore, Hisako Matsumoto, Cecile T J Holweg, John G Matthews, Joseph R Arron
Periostin is a matricellular protein that has been implicated in many disease states. It interacts with multiple signaling cascades to modulate the expression of downstream genes that regulate cellular interactions within the extracellular matrix. This review focuses on the role of periostin in respiratory diseases, including asthma and idiopathic pulmonary fibrosis, and its potential to help guide treatment or assess prognosis. Epithelial injury is a common feature of many respiratory diseases, resulting in the secretion, among others, of periostin, which is subsequently involved in airway remodeling and other aspects of pulmonary pathophysiology...
May 1, 2016: American Journal of Respiratory and Critical Care Medicine
Janice M Reichert
The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, are projected to gain first approvals in 2016...
2016: MAbs
Diego Jose Maselli, Holly Keyt, Linda Rogers
Interleukin (IL)-13 has been associated with multiple inflammatory features of asthma. It affects multiple cellular lines in asthma and is a key mediator in airway hyperreactivity and remodeling. Periostin, an extracellular protein, has been used as a surrogate marker of IL-13 activity and has been linked to airway remodeling by inducing subepithelial fibrosis. Lebrikizumab is a humanized monoclonal antibody that targets IL-13. Studies have demonstrated promising results with lebrikizumab therapy in asthma with regard to pulmonary function and exacerbation rates, especially on those patients with surrogate markers of T helper cell type 2-driven inflammation (ie, elevated immunoglobulin E levels, eosinophil counts, periostin levels)...
2015: Journal of Asthma and Allergy
R Andrew McIvor
OBJECTIVE: Asthma is a chronic inflammatory disorder of the airways with increasing worldwide prevalence. Despite treatment according to guidelines, a considerable proportion of patients with asthma remain symptomatic. Different potential therapeutic options for the treatment of these patients are currently in development and undergoing clinical trials, and it is important to regularly review their status. DATA SOURCES: A search of was performed and supported by a PubMed literature search and restricted to the previous 10 years to ensure currency of data...
October 2015: Annals of Allergy, Asthma & Immunology
Nicola A Hanania, Michael Noonan, Jonathan Corren, Phillip Korenblat, Yanan Zheng, Saloumeh K Fischer, Melissa Cheu, Wendy S Putnam, Elaine Murray, Heleen Scheerens, Cecile T J Holweg, Romeo Maciuca, Sarah Gray, Ramona Doyle, Dana McClintock, Julie Olsson, John G Matthews, Karl Yen
INTRODUCTION: In a subset of patients with asthma, standard-of-care treatment does not achieve disease control, highlighting the need for novel therapeutic approaches. Lebrikizumab is a humanised, monoclonal antibody that binds to and blocks interleukin-13 activity. METHODS: LUTE and VERSE were replicate, randomised, double-blind, placebo-controlled studies, evaluating multiple doses of lebrikizumab in patients with uncontrolled asthma despite the use of medium-to-high-dose inhaled corticosteroid and a second controller...
August 2015: Thorax
Francesco Menzella, Mirco Lusuardi, Carla Galeone, Luigi Zucchi
Patients with severe asthma or COPD have often a suboptimal symptom control due to inadequate treatment. A better understanding of pathogenetic mechanisms, phenotypes, endotypes and the new technologies available in the fields of molecular biology and immunogenetics have made it possible to synthesize specific monoclonal antibodies virtually able to interact with any target antigen, or to open a way for new therapeutic target options. At the moment, the only biologic drug available in clinical practice is omalizumab...
2015: Multidisciplinary Respiratory Medicine
David B Peden, Robert K Bush
In this review of articles published in the Journal in 2013, we report on the significant advances in environmental and occupational disorders. Research advances have led to the identification and defined the structure and function of several major allergens. A meta-analysis confirmed the importance of mold exposure in patients with allergic rhinitis, and a new immunologic classification of aspergillosis emerged. Insights into the role of diesel exhaust particles in patients with severe asthma were clarified...
May 2014: Journal of Allergy and Clinical Immunology
Santiago Quirce, Irina Bobolea, Javier Domínguez-Ortega, Pilar Barranco
Despite the administration of appropriate treatment, a high number of patients with asthma remain uncontrolled. This suggests the need for alternative treatments that are effective, safe and selective for the established asthma phenotypes, especially in patients with uncontrolled severe asthma. The most promising options among the new asthma treatments in development are biological therapies, particularly those monoclonal antibodies directed at selective targets. It should be noted that the different drugs, and especially the new biologics, act on very specific pathogenic pathways...
August 2014: Archivos de Bronconeumología
Mi-Ae Kim, Yoo Seob Shin, Le Duy Pham, Hae-Sim Park
PURPOSE OF REVIEW: A variety of novel asthma treatments have been developed based on phenotypes, and the clinical trial results show promising responses. This review summarizes the current knowledge of biomarkers for the determination of asthma phenotypes. RECENT FINDINGS: Eosinophilic inflammation is the most focused phenotype because most novel asthma treatments have targeted T-helper type 2 (Th2) pathway. Fractional-exhaled nitric oxide (FeNO) is a new method that represents an eosinophilic airway inflammation with a significant correlation with sputum eosinophilia and asthma severity instead of sputum eosinophil count that easily influenced by corticosteroid therapy...
February 2014: Current Opinion in Allergy and Clinical Immunology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"