University of California Los Angeles, Los Angeles, California.
Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, Texas.
Arthritis Rheumatol. 2024 Aug;76(8):1218-1229. doi: 10.1002/art.42846. Epub 2024 Apr 19.
The ORAL Surveillance trial found a dose-dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance.
Patients with rheumatoid arthritis (RA) aged 50 years or older with at least one additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (patients with first events/100 patient-years) by 6-month intervals were estimated for adjudicated VTE, deep vein thrombosis, and PE. Cox regression models identified risk factors. Clinical Disease Activity Index leading up to the event was explored in patients with VTE.
Cumulative probabilities for VTE and PE were higher with tofacitinib 10 mg BID, but not 5 mg BID, versus TNFi. Incidence rates were consistent across 6-month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index greater than or equal to 35 kg/m, older age, and history of chronic lung disease. At the time of the event, most patients with VTE had active disease as defined by Clinical Disease Activity Index.
Incidences of VTE and PE were higher with tofacitinib (10 > 5 mg BID) versus TNFi and were generally consistent over time. Across treatments, VTE risk factors were aligned with previous studies in the general RA population. These data highlight the importance of assessing VTE risk factors, including age, body mass index, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA.
ORAL Surveillance 试验发现与肿瘤坏死因子抑制剂（TNFi）相比，托法替布与剂量呈依赖性增加静脉血栓栓塞症（VTE）和肺栓塞（PE）事件。我们旨在评估 ORAL Surveillance 中随时间推移的 VTE 发生率，并探讨 VTE 的危险因素，包括疾病活动度。
年龄≥50 岁且至少有一个额外心血管危险因素的类风湿关节炎（RA）患者接受托法替布 5 或 10mg 每日两次（BID）或 TNFi 治疗。事后，按 6 个月间隔估算了经裁决的 VTE、深静脉血栓形成和 PE 的累积概率和发生率（每 100 名患者-年的首次发病例数）。Cox 回归模型确定了危险因素。对 VTE 患者的事件前临床疾病活动度指数进行了探讨。
与 TNFi 相比，托法替布 10mg BID 而非 5mg BID 的 VTE 和 PE 累积概率更高。各治疗组内 6 个月间隔的发生率一致。在各治疗组中，VTE 的危险因素包括既往 VTE、体重指数（BMI）≥35kg/m²、年龄较大和慢性肺部疾病史。在 VTE 发生时，大多数 VTE 患者的疾病活动度按临床疾病活动度指数定义为活跃。
与 TNFi 相比，托法替布（10mg BID＞5mg BID）的 VTE 和 PE 发生率更高，且随时间推移基本一致。在各治疗组中，VTE 的危险因素与一般 RA 人群中的既往研究一致。这些数据突出了在考虑启动托法替布或 TNFi 治疗活跃性 RA 患者时，评估 VTE 危险因素（包括年龄、BMI 和 VTE 史）的重要性。
