National Jewish Health and University of Colorado, Denver, Colorado.
Ann Allergy Asthma Immunol. 2016 Dec;117(6):577-581. doi: 10.1016/j.anai.2016.05.028.
Despite evidence demonstrating generally excellent therapeutic ratios for inhaled corticosteroids (ICSs) in asthma treatment, many clinicians and patients have ongoing concerns regarding their safety. To frame discussions of ICS safety, it is important to understand how safety is measured.
To discuss how ICS safety is and should be measured.
Discussion is augmented by relevant articles from the literature.
The therapeutic value of corticosteroids depends on the activation and repression of thousands of genes. However, it is not fully known which genes cause the desirable, therapeutic effects and which cause the adverse effects. The drug development process attempts to elucidate the clinically significant therapeutic effects and adverse effects of a candidate molecule and then compare them to those of currently available corticosteroids. Approaches to monitoring safety include clinical trials, retrospective comparison to historical efficacy and safety data, surrogate markers, animal models, and in vitro assays. Both preclinical and clinical data are used to compare safety among corticosteroids; however, no specific pathway or model that can robustly predict therapeutic ratios has been identified. Furthermore, variation in adverse effects is influenced by isoforms of the glucocorticoid receptor, differences in corticosteroid characteristics, differences among patients, and environmental variation.
Although some preclinical and patient-based metrics have predictive value, there is a clear need for improved biomarkers of corticosteroid adverse effects. Integrated analysis of preclinical and clinical data, including long-term safety data, could be used to address this important unmet need.
尽管有证据表明吸入性皮质类固醇（ICS）在哮喘治疗中通常具有出色的治疗效果比，但许多临床医生和患者仍然对其安全性存在持续担忧。为了说明 ICS 安全性问题，了解如何衡量安全性非常重要。
讨论如何衡量和应该衡量 ICS 的安全性。
讨论内容通过相关文献中的文章进行补充。
皮质类固醇的治疗价值取决于数千个基因的激活和抑制。然而，目前尚不完全清楚哪些基因会产生理想的治疗效果，哪些会产生不良反应。药物开发过程试图阐明候选分子的临床显著治疗效果和不良反应，然后将其与现有的皮质类固醇进行比较。监测安全性的方法包括临床试验、与历史疗效和安全性数据的回顾性比较、替代标志物、动物模型和体外检测。皮质类固醇的安全性评估既使用临床前数据，也使用临床数据；然而，尚未确定能够可靠预测治疗效果比的特定途径或模型。此外，不良反应的变异受糖皮质激素受体的同工型、皮质类固醇特性的差异、患者之间的差异以及环境变化的影响。
尽管一些临床前和基于患者的指标具有预测价值，但显然需要改进皮质类固醇不良反应的生物标志物。对包括长期安全性数据在内的临床前和临床数据进行综合分析，可用于解决这一重要的未满足需求。
