Abstract：
UNASSIGNED: Longitudinal changes in neurofilament light chain (NfL) levels were evaluated alongside prespecified clinical assessments 24 months into the patisiran Global open-label extension (OLE) study in patients with ATTRv amyloidosis with polyneuropathy.
UNASSIGNED: All patients enrolled in the Global OLE, from phase III APOLLO and phase II OLE parent studies, received patisiran. Assessments included measures of polyneuropathy (modified Neuropathy Impairment Score+7 (mNIS+7)), quality of life (QOL; Norfolk QOL-Diabetic Neuropathy questionnaire (Norfolk QOL-DN)), and plasma NfL.
UNASSIGNED: Patients receiving patisiran in the parent study (APOLLO-patisiran, n = 137; phase II OLE-patisiran, n = 25) demonstrated sustained improvements in mNIS+7 (mean change from parent study baseline (95% confidence interval): APOLLO-patisiran -4.8 (-8.9, -0.6); phase II OLE-patisiran -5.8 (-10.5, -1.2)) and Norfolk QOL-DN (APOLLO-patisiran -2.4 (-7.2, 2.3)), and maintained reduced NfL levels at Global OLE 24 months. After initiating patisiran in the Global OLE, APOLLO-placebo patients (n = 49) demonstrated stabilized mNIS+7, improved Norfolk QOL-DN, and significantly reduced NfL levels. Patisiran continued to demonstrate an acceptable safety profile. Earlier patisiran initiation was associated with a lower exposure-adjusted mortality rate.
UNASSIGNED: Long-term patisiran treatment led to sustained improvements in neuropathy and QOL, with NfL demonstrating potential as a biomarker for disease progression and treatment response in ATTRv amyloidosis with polyneuropathy.
UNASSIGNED: All patients enrolled in the Global OLE, from phase III APOLLO and phase II OLE parent studies, received patisiran. Assessments included measures of polyneuropathy (modified Neuropathy Impairment Score+7 (mNIS+7)), quality of life (QOL; Norfolk QOL-Diabetic Neuropathy questionnaire (Norfolk QOL-DN)), and plasma NfL.
UNASSIGNED: Patients receiving patisiran in the parent study (APOLLO-patisiran, n = 137; phase II OLE-patisiran, n = 25) demonstrated sustained improvements in mNIS+7 (mean change from parent study baseline (95% confidence interval): APOLLO-patisiran -4.8 (-8.9, -0.6); phase II OLE-patisiran -5.8 (-10.5, -1.2)) and Norfolk QOL-DN (APOLLO-patisiran -2.4 (-7.2, 2.3)), and maintained reduced NfL levels at Global OLE 24 months. After initiating patisiran in the Global OLE, APOLLO-placebo patients (n = 49) demonstrated stabilized mNIS+7, improved Norfolk QOL-DN, and significantly reduced NfL levels. Patisiran continued to demonstrate an acceptable safety profile. Earlier patisiran initiation was associated with a lower exposure-adjusted mortality rate.
UNASSIGNED: Long-term patisiran treatment led to sustained improvements in neuropathy and QOL, with NfL demonstrating potential as a biomarker for disease progression and treatment response in ATTRv amyloidosis with polyneuropathy.
摘要：
■在ATTRv淀粉样变伴多发性神经病变患者的patisiranGlobalOpen-labelextension(OLE)研究24个月后，与预先指定的临床评估一起评估神经丝轻链(NfL)水平的纵向变化。
■所有参加全球OLE的患者，来自III期APOLLO和II期OLE父母研究，收到patisiran。评估包括多发性神经病（改良神经病变损害评分+7（mNIS+7）），生活质量（QOL；诺福克QOL-糖尿病神经病变问卷（诺福克QOL-DN）），和血浆NfL。
■在母体研究中接受patisiran的患者（APOLLO-patisiran，n=137；II期OLE-patisiran，n=25）显示mNIS7的持续改善（与父母研究基线的平均变化（95％置信区间）：APOLLO-patisiran-4.8（-8.9，-0.6）；II期OLE-patisiran-5.8（-10.5，-1.2））和NorfolkQOL-DN（APOLLO-patisiran-2.4（-7.2，2.3））），并在全球OLE24个月保持降低的NfL水平。在全局OLE中启动patisiran后，APOLLO-安慰剂患者（n=49）表现出稳定的mNIS7，改善的诺福克QOL-DN，并显著降低NfL水平。Patisiran继续证明可接受的安全性。早期开始patisiran与较低的暴露校正死亡率相关。
■长期患者治疗可持续改善神经病变和生活质量，在ATTRv淀粉样变性伴多发性神经病中，NfL显示出作为疾病进展和治疗反应的生物标志物的潜力。
■所有参加全球OLE的患者，来自III期APOLLO和II期OLE父母研究，收到patisiran。评估包括多发性神经病（改良神经病变损害评分+7（mNIS+7）），生活质量（QOL；诺福克QOL-糖尿病神经病变问卷（诺福克QOL-DN）），和血浆NfL。
■在母体研究中接受patisiran的患者（APOLLO-patisiran，n=137；II期OLE-patisiran，n=25）显示mNIS7的持续改善（与父母研究基线的平均变化（95％置信区间）：APOLLO-patisiran-4.8（-8.9，-0.6）；II期OLE-patisiran-5.8（-10.5，-1.2））和NorfolkQOL-DN（APOLLO-patisiran-2.4（-7.2，2.3））），并在全球OLE24个月保持降低的NfL水平。在全局OLE中启动patisiran后，APOLLO-安慰剂患者（n=49）表现出稳定的mNIS7，改善的诺福克QOL-DN，并显著降低NfL水平。Patisiran继续证明可接受的安全性。早期开始patisiran与较低的暴露校正死亡率相关。
■长期患者治疗可持续改善神经病变和生活质量，在ATTRv淀粉样变性伴多发性神经病中，NfL显示出作为疾病进展和治疗反应的生物标志物的潜力。
