Patient stratification and the unmet need in asthma

详细信息    查看全文

• 作者：Linda Swedin¹ ; Tiiu Saarne¹ ; Maria Rehnberg ; Pernilla Glader ; Magdalena Niedzielska ; Gustav Johansson ; Petra Hazon ; Matthew C. Catley ; ^{matthew.catley@astrazeneca.com}
• 关键词：ACOS ; asthma and chronic obstructive pulmonary disease overlap syndrome ; ACQ ; Asthma Control Questionnaire ; AHR ; airway hyperresponsiveness ; ASM ; airway smooth muscle ; BAL ; bronchoalveolar lavage ; BHR ; bronchial hyperresponsiveness ; CLCA1 ; chloride channel ; calcium activated family member 1 ; COPD ; chronic obstructive pulmonary disease ; CRTh2 ; chemoattractant receptor-homologous molecule expressed on Th2 cells ; cysLTs ; cysteinyl leukotrienes ; DCs ; dendritic cells ; DPP-4 ; dipeptidyl peptidase-4 ; F
• 刊名：Pharmacology & Therapeutics
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：169
• 期：Complete
• 页码：13-34
• 全文大小：887 K
• 卷排序：169

文摘

Asthma is often described as an inflammatory disease of the lungs and in most patients symptomatic treatment with bronchodilators or inhaled corticosteroids is sufficient to control disease. Unfortunately there are a proportion of patients who fail to achieve control despite treatment with the best current treatment. These severe asthma patients have been considered a homogeneous group of patients that represent the unmet therapeutic need in asthma. Many novel therapies have been tested in unselected asthma patients and the effects have often been disappointing, particularly for the highly specific monoclonal antibody-based drugs such as anti-IL-13 and anti-IL-5. More recently, it has become clear that asthma is a syndrome with many different disease drivers. Clinical trials of anti-IL-13 and anti-IL-5 have focused on biomarker-defined patient groups and these trials have driven the clinical progression of these drugs. Work on asthma phenotyping indicates that there is a group of asthma patients where T helper cell type 2 (Th2) cytokines and inflammation predominate and these type 2 high (T2-high) patients can be defined by biomarkers and response to therapies targeting this type of immunity, including anti-IL-5 and anti-IL-13. However, there is still a subset of T2-low patients that do not respond to these new therapies. This T2-low group will represent the new unmet medical need now that the T2-high-targeting therapies have made it to the market. This review will examine the current thinking on patient stratification in asthma and the identification of the T2-high subset. It will also look at the T2-low patients and examine what may be the drivers of disease in these patients.