Alexander Veronica J, Prohaska Thomas A, Karwatowska-Prokopczuk Ewa, Xia Shuting, Tsimikas Sotirios
Ionis Pharmaceuticals, Inc., USA (Drs Alexander, Prohaska, Karwatowska-Prokopczuk, Xia, and Tsimikas).
Ionis Pharmaceuticals, Inc., USA (Drs Alexander, Prohaska, Karwatowska-Prokopczuk, Xia, and Tsimikas); University of California San Diego, USA (Dr Tsimikas).
J Clin Lipidol. 2025 May 20. doi: 10.1016/j.jacl.2025.05.007.
Olezarsen reduces acute pancreatitis events in patients with familial chylomicronemia syndrome (FCS). Lipase and amylase are biomarkers of acute pancreatitis released by the pancreas.
To assess whether routinely measured plasma levels of lipase and amylase are modified by treatment with olezarsen in patients with FCS.
Lipase and amylase were measured at baseline, and days 85, 169, 253, and 365 in patients randomly assigned to placebo, olezarsen 50 mg and 80 mg monthly for 365 days in the Balance trial.
Compared to placebo, significant differences were present in lipase levels in olezarsen 80 mg at days 85 (P = .026), 169 (P = .036) and 253 (P = .036) with a trend at day 365 (P = .096). Average percent change from baseline from day 1 to 365 revealed a mean (SD) percent increase in lipase of 12.6% (32.4) in placebo, a 6.7% (45.4) increase in olezarsen 50 mg (P = .26 vs placebo) and a reduction of -10.4% (22.7) in olezarsen 80 mg (P = .035 vs placebo) groups. In patients without a reported adverse event of abdominal pain, the placebo group showed a mean percent increase in lipase ranging from 7.91% to 39.1% from day 1 to day 365, olezarsen 50 mg -8.47% to 24.0%, and olezarsen 80 mg -15.4% to -29.6%, leading to significant differences at day 85 (P = .014), day 169 (P = .028), day 253 (P = .008), and day 365 (P = .045) (P-values vs placebo). Changes in amylase mirrored changes in lipase but did not reach statistical significance.
Changes in routinely measured lipase levels may reflect subclinical pancreatic injury. Olezarsen favorably modifies changes in lipase in patients with FCS.
奥莱扎森可减少家族性乳糜微粒血症综合征（FCS）患者的急性胰腺炎事件。脂肪酶和淀粉酶是胰腺释放的急性胰腺炎生物标志物。
评估FCS患者接受奥莱扎森治疗后，常规检测的血浆脂肪酶和淀粉酶水平是否会发生改变。
在平衡试验中，对随机分配接受安慰剂、每月50 mg和80 mg奥莱扎森治疗365天的患者，在基线以及第85、169、253和365天测量脂肪酶和淀粉酶水平。
与安慰剂相比，80 mg奥莱扎森组在第85天（P = 0.026）、169天（P = 0.036）和253天（P = 0.036）时脂肪酶水平存在显著差异，第365天有差异趋势（P = 0.096）。从第1天到365天相对于基线的平均百分比变化显示安慰剂组脂肪酶平均（标准差）增加12.6%（32.4），50 mg奥莱扎森组增加6.7%（45.4）（与安慰剂相比P = 0.26），80 mg奥莱扎森组降低-10.4%（22.7）（与安慰剂相比P = 0.035）。在未报告腹痛不良事件的患者中，安慰剂组从第1天到第365天脂肪酶平均百分比增加范围为7.91%至39.1%，50 mg奥莱扎森组为-8.47%至24.0%，80 mg奥莱扎森组为-15.4%至-29.6%，在第85天（P = 0.014）、169天（P = 0.028）、253天（P = 0.008）和365天（P = 0.045）导致显著差异（与安慰剂相比的P值）。淀粉酶的变化与脂肪酶的变化相似，但未达到统计学意义。
常规检测的脂肪酶水平变化可能反映亚临床胰腺损伤。奥莱扎森可改善FCS患者脂肪酶的变化。
