Department of Internal Medicine, Rheumatology, Pneumology, Nephrology and Diabetology, Medius Klinik Kirchheim/Teck, University of Tübingen, Kirchheim unter Teck, Germany.
Institute of Clinical Epidemiology and Applied Biometrics, University of Tübingen, Tubingen, Germany.
RMD Open. 2024 Feb 29;10(1):e003956. doi: 10.1136/rmdopen-2023-003956.
Glucocorticoids (GC) are a cornerstone in treating antineutrophil cytoplasmic antibodies-associated vasculitides (AAV), however, they add to morbidity and mortality. To date, GC toxicity in AAV has rarely been systematically investigated.
Patients with a confirmed AAV were included in this monocentric prospective study. GC toxicity was assessed by structured interviews, clinical examination and electronic medical record analysis. The Glucocorticoid Toxicity Index (GTI) consisting of the Aggregate Improvement Score (GTI-AIS) and the Cumulative Worsening Score (GTI-CWS) was assessed at two time points (t1 baseline, t2 6 months later). We used regression analyses to assess the relationship between GTI and GC exposure, toxicity, and disease activity, and a receiver operating characteristic analysis to calculate a GC threshold dose beyond which toxicity is expected to occur.
We included 138 patients with AAV. The median cumulative GC dose was 9014.0 mg. The most frequent adverse events were skin atrophy, osteoporosis and myopathy. GC exposure and toxicity were significantly correlated (p<0.001). GTI-AIS was significantly higher in active disease compared with patients in remission (p<0.001). GTI-CWS scored significantly higher in long-standing diseases (p=0.013) with high cumulative GC doses (p=0.003). Patients with a cumulative GC dose of 935 mg or more showed an 80% likelihood for a clinically meaningful change in GTI scoring.
The GTI is capable of capturing GC toxicity in AAV and identifies patients at increased risk for GC side effects. Our data support efforts to limit GC exposure in patients with AAV.
糖皮质激素（GC）是治疗抗中性粒细胞胞质抗体相关性血管炎（AAV）的基石，但会增加发病率和死亡率。迄今为止，AAV 中的 GC 毒性很少被系统研究。
本单中心前瞻性研究纳入了确诊的 AAV 患者。通过结构化访谈、临床检查和电子病历分析评估 GC 毒性。在两个时间点（t1 基线，t2 6 个月后）评估包含总改善评分（GTI-AIS）和累积恶化评分（GTI-CWS）的糖皮质激素毒性指数（GTI）。我们使用回归分析评估 GTI 与 GC 暴露、毒性和疾病活动之间的关系，并进行接收者操作特征分析以计算预计会发生毒性的 GC 阈值剂量。
我们纳入了 138 例 AAV 患者。GC 的累积剂量中位数为 9014.0mg。最常见的不良反应是皮肤萎缩、骨质疏松和肌病。GC 暴露和毒性呈显著相关（p<0.001）。与缓解期患者相比，活动期疾病患者的 GTI-AIS 显著升高（p<0.001）。长期疾病患者的 GTI-CWS 评分显著升高（p=0.013），且累积 GC 剂量较高（p=0.003）。累积 GC 剂量达到 935mg 或更高的患者，其 GTI 评分出现有临床意义变化的可能性为 80%。
GTI 能够捕捉 AAV 中的 GC 毒性，并识别出 GC 副作用风险增加的患者。我们的数据支持在 AAV 患者中限制 GC 暴露的努力。
