Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois.
Center for Pharmacoepidemiology & Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, Illinois.
Pharmacotherapy. 2019 Sep;39(9):921-928. doi: 10.1002/phar.2310. Epub 2019 Aug 6.
Bevacizumab is used in the treatment of recurrent glioblastoma, but evidence is limited on the incidence of thromboembolic complications regarding the use of this drug in real-world settings. We evaluated the risk of arterial thromboembolism (ATE) and venous thromboembolism (VTE) associated with the use of bevacizumab among adults diagnosed with high-grade gliomas in a commercially insured U.S.
Nested case-control study.
Truven Health MarketScan Commercial and Medicare Supplemental health claims databases (2009-2015).
A total of 2157 patients with high-grade gliomas who underwent incident (first-time) craniotomy, radiation, and concurrent temozolomide treatment between 2009 and 2015 were identified. Overall, 25 cases of ATE and 99 cases of VTE were each identified in this cohort, and each case was matched to up to 10 controls (170 for ATE and 819 for VTE) based on sex, age, quarter year of index time, and follow-up duration by using incidence density sampling without replacement from the overall cohort. Controls were at risk for the outcome of interest (ATE or VTE) at the time of case occurrence and survived at least as long as their referent case.
Exposure to bevacizumab was determined during inpatient or outpatient encounters between the index date (date of the incident craniotomy) and the ATE or VTE event or corresponding matched control date. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of ATE and VTE separately. A higher proportion of patients with ATE received bevacizumab compared with controls (28% vs 17%; adjusted OR 1.51, 95% CI 0.54-4.24), but this excess in odds was not statistically significant. Similarly, bevacizumab was not significantly associated with VTE (13% vs 9%; adjusted OR 1.40, 95% CI 0.71-2.75).
We found no significant association between the use of bevacizumab and the occurrence of thromboembolic events in patients with high-grade gliomas, although our study was limited by the small number of ATE events. Because the potential for complications from arterial thrombosis cannot be completely ruled out, further research is needed to confirm the thromboembolic safety of bevacizumab in a larger sample of patients with high-grade gliomas.
贝伐单抗用于复发性胶质母细胞瘤的治疗，但在真实环境中使用该药的血栓栓塞并发症发生率方面，证据有限。我们评估了在接受高等级脑胶质瘤治疗的成年人中使用贝伐单抗与动脉血栓栓塞（ATE）和静脉血栓栓塞（VTE）相关的风险。
巢式病例对照研究。
Truven Health MarketScan 商业和医疗保险补充健康索赔数据库（2009-2015 年）。
共确定了 2157 名接受高等级脑胶质瘤初次（首次）开颅手术、放疗和同期替莫唑胺治疗的患者，这些患者均在 2009 年至 2015 年期间进行了手术。在该队列中，共发现 25 例 ATE 和 99 例 VTE，根据性别、年龄、指数时间季度、采用无替换的发生率密度抽样，为每个病例匹配了多达 10 个对照（ATE 为 170 例，VTE 为 819 例），并从整个队列中进行匹配。对照组在发生病例时存在感兴趣的结局（ATE 或 VTE）的风险，且至少与参考病例存活时间一样长。
贝伐单抗的暴露情况是根据索引日期（开颅手术日期）和 ATE 或 VTE 事件或相应匹配对照日期之间的住院或门诊就诊情况确定的。采用多变量条件逻辑回归模型分别估计 ATE 和 VTE 风险的比值比（OR）和 95%置信区间（CI）。与对照组相比，ATE 患者接受贝伐单抗治疗的比例更高（28% vs. 17%；调整后的 OR 1.51，95%CI 0.54-4.24），但这一优势在统计学上并不显著。同样，贝伐单抗与 VTE 无显著相关性（13% vs. 9%；调整后的 OR 1.40，95%CI 0.71-2.75）。
我们发现，在接受高等级脑胶质瘤治疗的患者中，贝伐单抗的使用与血栓栓塞事件的发生之间无显著关联，尽管我们的研究受到 ATE 事件数量较少的限制。由于不能完全排除动脉血栓形成并发症的风险，因此需要进一步的研究来确认在更大样本量的高等级脑胶质瘤患者中贝伐单抗的血栓栓塞安全性。
