Abstract：
OBJECTIVE: Evaluating cardiovascular safety of sphingosine 1-phosphate (S1P) receptor modulators is warranted due to S1P receptor expression on cardiomyocytes and vascular endothelial cells. This analysis reports the cardiovascular safety of ozanimod, an S1P receptor modulator, in patients with moderately to severely active ulcerative colitis from the phase 3 True North (TN) and open-label extension (OLE).
METHODS: All patients who received ozanimod in TN (n = 796) and all eligible TN patients who entered the OLE (n = 823) were included. Cardiovascular-related adverse events were evaluated in patients with up to 146 weeks of ozanimod exposure (2219 patient-years), which included 52 weeks during TN.
RESULTS: On TN day 1, first-dose ozanimod resulted in a 0.2 beats per minute mean decrease in heart rate from pretreatment to hour 6; 2 patients experienced bradycardia, which resolved without treatment modification. Mean systolic and diastolic blood pressure increases of 5.1 and 2.2 mm Hg, respectively, were observed at TN week 52. No second-degree Mobitz type II atrioventricular block events were reported; 1 third-degree atrioventricular block unrelated to ozanimod occurred in the OLE. Cardiac and vascular treatment-emergent adverse events were infrequent (3.8% [31 of 823] and 8.5% [70 of 823]); no ozanimod-related cardiovascular deaths occurred. The incidences of deep-vein thrombosis (0.2%; 2 of 823), pulmonary embolism (0.2%; 2 of 823), and ischemic stroke (0.4%; 3 of 823) in the OLE were low.
CONCLUSIONS: No new cardiovascular safety signals were identified, consistent with findings from previous ozanimod studies. There were few major adverse cardiovascular events or thromboembolic events, which were unrelated or unlikely related to ozanimod. Ozanimod has a well-tolerated cardiovascular safety profile when prescribed in accordance with the label. Clinical trial registry website and trial numbers: ClinicalTrials.gov numbers: NCT02435992 and NCT02531126.
METHODS: All patients who received ozanimod in TN (n = 796) and all eligible TN patients who entered the OLE (n = 823) were included. Cardiovascular-related adverse events were evaluated in patients with up to 146 weeks of ozanimod exposure (2219 patient-years), which included 52 weeks during TN.
RESULTS: On TN day 1, first-dose ozanimod resulted in a 0.2 beats per minute mean decrease in heart rate from pretreatment to hour 6; 2 patients experienced bradycardia, which resolved without treatment modification. Mean systolic and diastolic blood pressure increases of 5.1 and 2.2 mm Hg, respectively, were observed at TN week 52. No second-degree Mobitz type II atrioventricular block events were reported; 1 third-degree atrioventricular block unrelated to ozanimod occurred in the OLE. Cardiac and vascular treatment-emergent adverse events were infrequent (3.8% [31 of 823] and 8.5% [70 of 823]); no ozanimod-related cardiovascular deaths occurred. The incidences of deep-vein thrombosis (0.2%; 2 of 823), pulmonary embolism (0.2%; 2 of 823), and ischemic stroke (0.4%; 3 of 823) in the OLE were low.
CONCLUSIONS: No new cardiovascular safety signals were identified, consistent with findings from previous ozanimod studies. There were few major adverse cardiovascular events or thromboembolic events, which were unrelated or unlikely related to ozanimod. Ozanimod has a well-tolerated cardiovascular safety profile when prescribed in accordance with the label. Clinical trial registry website and trial numbers: ClinicalTrials.gov numbers: NCT02435992 and NCT02531126.
摘要：
目的：由于S1P受体在心肌细胞和血管内皮细胞上的表达，因此有必要评估1-磷酸鞘氨醇（S1P）受体调节剂的心血管安全性。这项分析报告了奥扎马德的心血管安全性，S1P受体调节剂，从3期真北（TN）和开放标签延伸（OLE）患有中度至重度活动性溃疡性结肠炎的患者。
方法：纳入所有在TN中接受ozanimod的患者（n=796）和所有进入OLE的合格TN患者（n=823）。心血管相关不良事件（AEs）在奥扎马德暴露达146周（2219患者-年）的患者中进行评估，其中包括TN期间的52周。
结果：在TN第1天，第一剂奥扎马德导致心率从预处理到6小时平均下降0.2bpm；2例患者出现心动过缓，在没有修改治疗的情况下解决了。平均收缩压和舒张压分别增加5.1和2.2mmHg，分别,在TN第52周观察到。未报告二度MobitzII型房室传导阻滞事件；在OLE中发生了1例与奥扎马德无关的三度房室传导阻滞。心脏和血管治疗引起的AE很少发生（3.8％[31/823]和8.5％[70/823]）；没有发生与奥扎尼德相关的心血管死亡。深静脉血栓的发生率(0.2%[2/823]),肺栓塞(0.2%[2/823]),OLE患者的缺血性卒中(0.4%[3/823])较低。
结论：没有发现新的心血管安全信号，与以前的奥扎马德研究结果一致。很少有重大不良心血管事件或血栓栓塞事件。与奥扎马德无关或不太可能有关。根据标签规定，Ozanimod具有良好的耐受性心血管安全性。
方法：纳入所有在TN中接受ozanimod的患者（n=796）和所有进入OLE的合格TN患者（n=823）。心血管相关不良事件（AEs）在奥扎马德暴露达146周（2219患者-年）的患者中进行评估，其中包括TN期间的52周。
结果：在TN第1天，第一剂奥扎马德导致心率从预处理到6小时平均下降0.2bpm；2例患者出现心动过缓，在没有修改治疗的情况下解决了。平均收缩压和舒张压分别增加5.1和2.2mmHg，分别,在TN第52周观察到。未报告二度MobitzII型房室传导阻滞事件；在OLE中发生了1例与奥扎马德无关的三度房室传导阻滞。心脏和血管治疗引起的AE很少发生（3.8％[31/823]和8.5％[70/823]）；没有发生与奥扎尼德相关的心血管死亡。深静脉血栓的发生率(0.2%[2/823]),肺栓塞(0.2%[2/823]),OLE患者的缺血性卒中(0.4%[3/823])较低。
结论：没有发现新的心血管安全信号，与以前的奥扎马德研究结果一致。很少有重大不良心血管事件或血栓栓塞事件。与奥扎马德无关或不太可能有关。根据标签规定，Ozanimod具有良好的耐受性心血管安全性。
