Team Pharmacoepidemiology, Univ. Bordeaux, INSERM, CHU de Bordeaux, Pôle de santé publique, Service de Pharmacologie Médicale, U1219F-33000, Bordeaux, BPH, France.
Service de Rhumatologie, Université de Paris, Hôpital Cochin, AP-HP.CUP, Paris, France.
Eur J Clin Pharmacol. 2022 Dec;78(12):1981-1990. doi: 10.1007/s00228-022-03402-2. Epub 2022 Oct 26.
JAK-inhibitors (JAK-i) might be associated with venous (VTE) and arterial thromboembolic events (ATE). To evaluate the association between JAK-i and the risk of VTE and ATE.
A self-controlled case series was performed using data from the nationwide French healthcare insurance system database SNDS. We included all patients treated with JAK-i (baricitinib or tofacitinib), and having presented at least one VTE or ATE between November 1, 2017 and June 30, 2019. Associations were estimated using the incident rate ratio (IRR). Two post-exposure periods (until day 30 and until day 60) were individualized.
Among 5870 patients with JAK-i dispensing, 92 had an incident VTE or ATE within the study period. Their median age at JAK-i initiation was 65.7 years [IQR: 56.1-75.8] and 65.2% were female (n = 60). Before event incidence, 65.2% (n = 60) received baricitinib, 32.6% (n = 30) tofacitinib and 2.2% (n = 2) had both medications. Moreover, 41.3% (n = 38) presented a VTE and 58.7% (n = 54) an ATE. The median time-to-onset after JAK-i initiation was 4.6 months [IQR: 2.5-9.2] for VTE and 6.1 months [IQR: 3.0-8.5] for ATE. An IRR of 8.27 (95% CI 3.41-20.04) for VTE was detected during JAK-i treatment and remained increased over the 30-day period of post-exposure (6.52 [2.02-21.11]). An IRR of 9.27 (3.68-23.34) was also found for ATE, which remained increased over the 30-day period of post-exposure (10.12 [3.27-31.37]). No increased risk was detected during long-term post-exposure for either VTE or ATE.
This study shows evidence of an increased risk of VTE and ATE associated with the use of baricitinib and tofacitinib.
JAK 抑制剂（JAK-i）可能与静脉血栓栓塞症（VTE）和动脉血栓栓塞事件（ATE）相关。本研究旨在评估 JAK-i 与 VTE 和 ATE 风险之间的关联。
本研究采用来自法国全国性医疗保险系统数据库 SNDS 的数据开展了一项自我对照病例系列研究。我们纳入了所有接受 JAK-i（巴瑞替尼或托法替布）治疗且在 2017 年 11 月 1 日至 2019 年 6 月 30 日期间至少发生过一次 VTE 或 ATE 的患者。采用发病率比值比（IRR）评估关联。针对两种暴露后时期（暴露后 30 天和暴露后 60 天）进行个体化分析。
在 5870 名接受 JAK-i 治疗的患者中，92 名患者在研究期间发生了 VTE 或 ATE。他们接受 JAK-i 治疗时的中位年龄为 65.7 岁[四分位距（IQR）：56.1-75.8]，65.2%为女性（n=60）。在事件发生之前，65.2%（n=60）接受了巴瑞替尼治疗，32.6%（n=30）接受了托法替布治疗，2.2%（n=2）同时接受了这两种药物治疗。此外，41.3%（n=38）发生 VTE，58.7%（n=54）发生 ATE。VTE 的中位发病时间为 JAK-i 治疗后 4.6 个月[IQR：2.5-9.2]，ATE 的中位发病时间为 6.1 个月[IQR：3.0-8.5]。在 JAK-i 治疗期间，VTE 的发病率比值比（IRR）为 8.27（95%CI 3.41-20.04），且在暴露后 30 天内仍呈上升趋势（6.52[2.02-21.11]）。ATE 的 IRR 也为 9.27（3.68-23.34），在暴露后 30 天内仍呈上升趋势（10.12[3.27-31.37]）。在暴露后长期随访期间，VTE 或 ATE 均未检测到风险增加。
本研究结果表明，巴瑞替尼和托法替布的使用与 VTE 和 ATE 风险增加相关。
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