Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States.
Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States.
Semin Arthritis Rheum. 2022 Aug;55:152010. doi: 10.1016/j.semarthrit.2022.152010. Epub 2022 Apr 15.
Glucocorticoids (GCs) have been the cornerstone of treating dozens of inflammatory conditions for more than seven decades. GC toxicity is ubiquitous in both clinical trials and clinical practice, and toxicities associated with GC use are central to the experience of most patients being treated for immune-mediated conditions. These conditions span the full range of medical specialties, including rheumatology, nephrology, gastroenterology, neurology, pulmonology, ophthalmology, and others. One of the goals of novel therapies for inflammatory disease must be to diminish the effects of GC toxicity in clinically important ways, thereby differentiating these new treatments from existing approaches. Despite the importance of glucocorticoids in the treatment of inflammatory disease for more than 70 years, no reliable means of calculating the degree to which GC toxicity has worsened or improved over the course of treatment has been available. The Glucocorticoid Toxicity Index (GTI), developed by an international group of subspecialty physician experts as a clinician-facing clinical trials outcome measure, is a standardized, validated measure of the phenomenon known as GC toxicity. The purpose of the instrument is to measure change in GC toxicity between two points in time: for example, between the baseline visit and the time of the primary efficacy outcome assessment. The instrument is designed to quantify both worsening and improvement in GC toxicity. The GTI has been validated in both real-world experiences and clinical trials, including a phase 3, label-enabling trial in ANCA associated vasculitis. This article reviews the history and rationale for the development of the GTI, describes key data from validation studies, considers the minimum clinically important difference, and provides instructions for use of the instrument.
糖皮质激素（GCs）在过去七十多年中一直是治疗数十种炎症性疾病的基石。GC 毒性在临床试验和临床实践中普遍存在，与 GC 使用相关的毒性是大多数接受免疫介导性疾病治疗的患者体验的核心。这些疾病涵盖了从风湿病学、肾脏病学、胃肠病学、神经病学、肺病学、眼科学到其他医学专业的所有领域。炎症性疾病新疗法的目标之一必须是在临床上以重要方式减轻 GC 毒性的影响，从而使这些新疗法与现有方法区分开来。尽管糖皮质激素在炎症性疾病的治疗中已有 70 多年的历史，但在治疗过程中，仍缺乏可靠的方法来计算 GC 毒性恶化或改善的程度。由国际专家组成的亚专科医生团队开发的糖皮质激素毒性指数（GTI）是一种面向临床医生的临床试验结局衡量标准，是一种标准化、经过验证的 GC 毒性现象的衡量标准。该工具的目的是衡量两个时间点之间 GC 毒性的变化：例如，从基线就诊到主要疗效评估时间。该仪器旨在量化 GC 毒性的恶化和改善。GTI 已在真实世界的经验和临床试验中得到验证，包括在抗中性粒细胞胞浆抗体相关性血管炎的 3 期、标签启用试验中。本文回顾了 GTI 的发展历史和原理，描述了验证研究中的关键数据，考虑了最小临床重要差异，并提供了该仪器的使用说明。
