Abstract：
Data regarding the safety of co-administration of ibrutinib with anticoagulants in real-life settings are scarce. Using a nationwide database, we conducted a nested case-control study in a cohort of new users of ibrutinib to assess the risk of clinically relevant bleeding (CRB) associated with anticoagulation. Cases were patients with a diagnosis of CRB, defined as hospitalization with a diagnosis of bleeding. The date of CRB constituted the index date. Up to four controls were matched on sex, age at index date and duration of follow-up. The risk of CRB associated with anticoagulation in patients receiving ibrutinib was estimated using conditional logistic regression models, providing odds ratios (OR) adjusted for risk factors of bleeding. Among 614 cases and 2407 matched controls, the risk of CRB was significantly higher in patients receiving both ibrutinib and anticoagulants (adjusted OR [aOR] 2.54, confidence interval [CI] 95% [1.94; 3.32]). When considering anticoagulant class, aOR was 1.99 (CI 95% [1.19; 3.33]) for VKA, 2.48 (CI 95% [1.76; 3.47]) for direct oral anticoagulants and 3.40 (CI 95% [2.01; 5.75]) for parenteral anticoagulants. In conclusion, this study found a 2.5-fold increased risk of CRB in patients receiving both ibrutinib and anticoagulants in real-life settings, and similar aOR among oral anticoagulants.
摘要：
在现实生活中，伊布替尼与抗凝剂联合给药的安全性数据很少。使用全国性的数据库，我们在依鲁替尼的新使用者队列中进行了巢式病例对照研究,以评估与抗凝相关的临床相关出血(CRB)的风险.病例为诊断为CRB的患者，定义为诊断为出血的住院。CRB的日期构成索引日期。多达四个对照在性别上匹配，索引日期的年龄和随访时间。使用条件逻辑回归模型估计接受依鲁替尼治疗的患者与抗凝相关的CRB风险，提供根据出血危险因素调整的比值比(OR).在614例病例和2407例匹配的对照中，同时接受依鲁替尼和抗凝药的患者的CRB风险显著较高(校正OR[aOR]2.54,置信区间[CI]95%[1.94;3.32]).当考虑抗凝剂类别时，对于VKA，OR为1.99(CI95%[1.19;3.33])，直接口服抗凝剂为2.48（CI95%[1.76;3.47]），肠胃外抗凝剂为3.40（CI95%[2.01;5.75]）。总之,这项研究发现，在现实生活中同时接受依鲁替尼和抗凝剂的患者中，CRB的风险增加了2.5倍，和类似的aOR在口服抗凝剂。
