Abstract

Introduction: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, fatal, multisystem disease leading to deteriorating quality of life (QOL). The impact of patisiran on QOL in patients with hATTR amyloidosis with polyneuropathy from the phase 3 APOLLO study (NCT01960348) is evaluated.

Methods: Patients received either patisiran 0.3 mg/kg (n = 148) or placebo (n = 77) intravenously once every three weeks for 18 months. Multiple measures were used to assess varying aspects of QOL.

Results: At 18 months, compared with placebo, patisiran improved Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) score; (least squares [LS] mean difference: −21.1; p = 1.10 × 10⁻¹⁰; improved across all domains), EuroQoL 5-dimensions 5-levels (LS mean difference: 0.2; p = 1.4 × 10⁻¹²), EuroQoL-visual analog scale (LS mean difference: 9.5; p=.0004), Rasch-built Overall Disability Scale (LS mean difference: 9.0; p = 4.07 × 10⁻¹⁶) and Composite Autonomic Symptom Score-31(COMPASS-31; LS mean difference: −7.5; p=.0008). Placebo-treated patients experienced rapid QOL deterioration; treatment effects for patisiran were observed as early as 9 months. At 18 months, patisiran improved Norfolk QOL-DN total score and three individual domains as well as COMPASS-31 total scores relative to baseline. Consistent benefits were also observed in the cardiac subpopulation.

Conclusion: The benefits of patisiran across all QOL measures and the rapid deterioration observed with placebo, highlight the urgency in early treatment for patients with hATTR amyloidosis with polyneuropathy.

摘要

简介：遗传性甲状腺素介导的（hATTR）淀粉样变性病是一种罕见的致命性多系统疾病，可导致生活质量（QOL）下降。通过3期APOLLO研究（NCT01960348），评估了patisiran对患有多发性神经病的hATTR淀粉样变性病患者的QOL的影响。

方法：患者 每三个星期静脉注射一次patisiran 0.3 mg / kg（n  = 148）或安慰剂（n = 77），共18个月。使用多种方法来评估QOL的各个方面。

结果：与安慰剂相比，在18个月时，patisiran改善了诺福克糖尿病生活质量神经病（Norfolk QOL-DN）评分；（最小二乘[LS]平均差：−21.1；p  = 1.10×10 ^-10；在所有领域均得到改善），EuroQoL 5维5级（LS平均差：0.2；p  = 1.4×10 ^-12），EuroQoL -视觉模拟量表（LS平均差异：9.5; p = .0004），Rasch建立的总体残疾量表（LS平均差异：9.0; p  = 4.07×10 ^-16）和复合自主神经症状评分-31（COMPASS-31; LS平均差：−7.5; p= .0008）。接受安慰剂治疗的患者的生活质量迅速恶化；早在9个月就观察到了patisiran的治疗效果。在18个月时，patisiran相对于基线改善了Norfolk QOL-DN总得分和三个独立领域以及COMPASS-31总得分。在心脏亚群中也观察到一致的益处。

结论： patisiran在所有QOL措施中的益处以及使用安慰剂观察到的快速恶化，突显了hATTR淀粉样变性伴多发性神经病患者早期治疗的紧迫性。