在类风湿关节炎、银屑病关节炎和强直性脊柱炎的 upadacitinib 临床试验项目中，MACE 和 VTE 事件。

MACE and VTE across upadacitinib clinical trial programmes in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

机构信息

Division of Rheumatology, University of California Los Angeles, Los Angeles, California, USA

Division of Infection and Immunity, CREATE Centre, Cardiff University, Cardiff, UK.

出版信息

RMD Open. 2023 Nov;9(4). doi: 10.1136/rmdopen-2023-003392.

OBJECTIVES

To provide an integrated analysis of major adverse cardiovascular events (MACEs) and events of venous thromboembolism (VTE) and associated risk factors across rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) phase 2b/3 upadacitinib clinical programmes.

METHODS

Data were analysed and summarised from clinical trials of RA, PsA and AS treated with upadacitinib 15 mg once daily (QD) and 30 mg QD (as of 30 June 2021). Data from adalimumab (RA and PsA) and methotrexate (RA) arms were included as comparators. Adjudicated MACEs and VTE events were presented as exposure-adjusted rates per 100 patient-years (E/100 PY). Univariable Cox proportional hazard regression analyses assessed potential associations of risk factors for MACE and VTE.

RESULTS

In total, 4298 patients received upadacitinib 15 mg (RA n=3209, PsA n=907 and AS n=182) and 2125 patients received upadacitinib 30 mg (RA n=1204 and PsA n=921). In patients with RA and PsA, rates of MACE (0.3-0.6 E/100 PY) and VTE (0.2-0.4 E/100 PY) were similar across upadacitinib doses; in patients with AS, no MACEs and one VTE event occurred. Most patients experiencing MACEs or VTE events had two or more baseline cardiovascular risk factors. Across RA and PsA groups, rates of MACEs and VTE events were similar.

CONCLUSIONS

Rates of MACEs and VTE events with upadacitinib were consistent with previously reported data for patients receiving conventional synthetic and biologic disease-modifying anti-rheumatic drugs and comparable with active comparators adalimumab and methotrexate. Associated patient characteristics are known risk factors for MACEs and VTE events.

TRIAL REGISTRATION NUMBERS

RA (SELECT-NEXT: NCT02675426; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847; SELECT-COMPARE: NCT02629159; SELECT-EARLY: NCT02706873, SELECT-CHOICE: NCT03086343), PsA (SELECT-PsA 2: NCT03104374; SELECT-PsA 1: NCT03104400), and AS (SELECT-AXIS 1: NCT03178487).

目的

对接受巴瑞替尼治疗的类风湿关节炎（RA）、银屑病关节炎（PsA）和强直性脊柱炎（AS）患者的主要不良心血管事件（MACE）和静脉血栓栓塞（VTE）事件以及相关风险因素进行综合分析。

方法

对截至 2021 年 6 月 30 日接受巴瑞替尼 15mg 每日一次（QD）和 30mg QD 治疗的 RA、PsA 和 AS 的临床研究数据进行分析和总结。阿达木单抗（RA 和 PsA）和甲氨蝶呤（RA）臂的数据被用作对照。经裁决的 MACE 和 VTE 事件以每 100 患者-年（E/100PY）的暴露调整发生率（E/100PY）呈现。单变量 Cox 比例风险回归分析评估了 MACE 和 VTE 的风险因素的潜在关联。

结果

共有 4298 例患者接受了巴瑞替尼 15mg（RA n=3209，PsA n=907，AS n=182），2125 例患者接受了巴瑞替尼 30mg（RA n=1204，PsA n=921）。在 RA 和 PsA 患者中，巴瑞替尼的 MACE（0.3-0.6 E/100PY）和 VTE（0.2-0.4 E/100PY）发生率相似；在 AS 患者中，没有发生 MACE 事件，但有一例 VTE 事件。大多数发生 MACE 或 VTE 事件的患者有两个或更多的基线心血管风险因素。在 RA 和 PsA 组中，MACE 和 VTE 事件的发生率相似。

结论

巴瑞替尼的 MACE 和 VTE 事件发生率与接受传统合成和生物疾病修饰抗风湿药物治疗的患者的先前报告数据一致，且与阿达木单抗和甲氨蝶呤等活性对照药物相当。相关患者特征是 MACE 和 VTE 事件的已知危险因素。

试验注册编号

RA（SELECT-NEXT：NCT02675426；SELECT-MONOTHERAPY：NCT02706951；SELECT-BEYOND：NCT02706847；SELECT-COMPARE：NCT02629159；SELECT-EARLY：NCT02706873，SELECT-CHOICE：NCT03086343），PsA（SELECT-PsA 2：NCT03104374；SELECT-PsA 1：NCT03104400）和 AS（SELECT-AXIS 1：NCT03178487）。