Upadacitinib 在拉丁美洲类风湿关节炎患者中的安全性：SELECT 阶段 3 临床项目的综合安全性分析。
Safety of upadacitinib in Latin American patients with rheumatoid arthritis: an integrated safety analysis of the SELECT phase 3 clinical program.
机构信息
Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Universidade Federal Do Paraná, Curitiba, PR, Brazil.
出版信息
Clin Rheumatol. 2023 May;42(5):1249-1258. doi: 10.1007/s10067-023-06513-y. Epub 2023 Jan 30.
INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by ongoing inflammation and degradation of synovial joints. The oral JAK inhibitor, upadacitinib, is approved for RA. We conducted an integrated safety analysis of upadacitinib 15 mg once daily (QD) in patients from Latin America (LATAM) versus the rest of the world (RoW).
METHODS
Treatment-emergent adverse events (AEs) and laboratory data from six phase 3, randomized controlled trials, adjusted for upadacitinib 15 mg QD use in RA, were analyzed.
RESULTS
Overall, 3209 patients received upadacitinib 15 mg QD for 7024 patient-years (PY). LATAM patients (n = 725) had a mean upadacitinib exposure of 1518 PY. Baseline characteristics were generally similar between LATAM and RoW populations. AE rates (including serious/opportunistic infections, tuberculosis, and herpes zoster) and deaths were comparable between populations. LATAM patients had lower serious AE rates per 100 PY (9.4 vs 14.0 E/100 PY) and discontinuation-related AEs (3.9 vs 6.0 E/100 PY) versus RoW. Rates of cardiovascular events were low (≤ 0.5 E/100 PY) and similar between populations. Malignancies, excluding non-melanoma skin cancer, were less common in the LATAM population versus RoW (0.2 vs 1.0 E/100 PY). Laboratory abnormalities were similar between populations, with decreases in hemoglobin, lymphocyte, and neutrophil counts, and elevations in liver enzymes and creatine phosphokinase. Mean change from baseline in low- and high-density lipoprotein cholesterol was generally comparable between LATAM and RoW populations.
CONCLUSION
Upadacitinib 15 mg QD demonstrated a consistent safety profile across LATAM and RoW patient populations, with no new safety risks observed.
TRIAL REGISTRATION NUMBERS
SELECT-EARLY, NCT02706873; SELECT-NEXT, NCT02675426; SELECT-COMPARE, NCT02629159; SELECT-MONOTHERAPY, NCT02706951; SELECT-BEYOND, NCT02706847; SELECT-CHOICE, NCT03086343.
介绍/目的：类风湿关节炎（RA）是一种慢性自身免疫性疾病，其特征为持续的炎症和滑膜关节的退化。口服 JAK 抑制剂乌帕替尼（upadacitinib）已获批用于 RA 治疗。我们对拉丁美洲（LATAM）与世界其他地区（RoW）接受乌帕替尼 15mg 每日一次（QD）治疗的患者进行了综合安全性分析。
方法
对六项 3 期、随机对照试验中调整乌帕替尼 15mg QD 治疗 RA 的使用后出现的治疗期不良事件（AE）和实验室数据进行分析。
结果
共有 3209 例患者接受乌帕替尼 15mg QD 治疗，共 7024 患者-年（PY）。LATAM 患者（n=725）的乌帕替尼暴露平均为 1518 PY。LATAM 和 RoW 人群的基线特征一般相似。AE 发生率（包括严重/机会性感染、结核病和带状疱疹）和死亡率在人群之间相当。与 RoW 相比，LATAM 患者的严重 AE 发生率更低（每 100 PY 为 9.4 vs 14.0 E/100 PY），且与停药相关的 AE 发生率更低（每 100 PY 为 3.9 vs 6.0 E/100 PY）。心血管事件发生率较低（≤0.5 E/100 PY），且在人群之间相似。LATAM 人群的恶性肿瘤（不包括非黑色素瘤皮肤癌）发生率低于 RoW（每 100 PY 为 0.2 vs 1.0 E/100 PY）。人群之间的实验室异常情况相似，血红蛋白、淋巴细胞和中性粒细胞计数降低，肝酶和肌酸磷酸激酶升高。LATAM 和 RoW 人群的低密度脂蛋白胆固醇和高密度脂蛋白胆固醇的平均基线变化基本相当。
结论
乌帕替尼 15mg QD 在 LATAM 和 RoW 患者人群中表现出一致的安全性特征，未观察到新的安全性风险。
试验注册编号
SELECT-EARLY，NCT02706873；SELECT-NEXT，NCT02675426；SELECT-COMPARE，NCT02629159；SELECT-MONOTHERAPY，NCT02706951；SELECT-BEYOND，NCT02706847；SELECT-CHOICE，NCT03086343。
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