Impact of baseline polyneuropathy severity on patisiran treatment outcomes in the APOLLO trial
Impact of baseline polyneuropathy severity on patisiran treatment outcomes in the APOLLO trial
复制标题
APOLLO 试验中基线多发性神经病严重程度对 patisiran 治疗结果的影响
DOI：
10.1080/13506129.2022.2118043
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发表时间：
2023
期刊：
影响因子：
5.5
通讯作者：
Adams D.
中科院分区：
文献类型：
--
作者：
Quan D;Obici L;Berk JL;Ando Y;Aldinc E;White MT;Adams D.
目的评估遗传性转甲状腺素介导淀粉样变性（ATTRv淀粉样变性）患者的基线多神经病变严重程度如何影响帕西兰对神经功能损害和生活质量（QOL）的反应。方法：本后期分析将3期APOLLO研究的患者（n= 225）按基线神经病变损害评分（NIS）分为四分位数：6 - <31；31 - < 57;57 - < 85.5;85.5 - -141.6。评估神经功能障碍（改良NIS+7 [mNIS+7]， NIS总分）、残疾（Rasch-built Overall disability Scale [R-ODS]）、步速（10米步行测试[10-MWT]）、握力、QOL （Norfolk生活质量-糖尿病神经病变[Norfolk QOL- dn]问卷）。结果在所有基线NIS四分位数中，与安慰剂相比，patisiran在18个月时改善了几种疾病的临床标志物。较低NIS四分位数的患者，在病程早期接受帕西兰治疗，与较高NIS四分位数的患者相比，在mNIS+7、NIS总分、R-ODS、10-MWT、握力和Norfolk QOL-DN方面保持了更好的评分，而安慰剂治疗的患者在18个月后所有四分位数的所有功能测量都出现了恶化。结论：与安慰剂相比，spatisiran治疗改善了大范围基线多神经病变严重程度的神经功能和生活质量。对于ATTRv淀粉样变患者，开始治疗的时机仍然是维持功能的关键。
ObjectiveAssess how baseline polyneuropathy severity impacts response to patisiran regarding neurologic impairment and quality of life (QOL) in patients with hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis).MethodsThispost hocanalysis grouped patients from the Phase 3 APOLLO study (n= 225) by baseline Neuropathy Impairment Score (NIS) into quartiles: 6–<31; 31–<57; 57–<85.5; 85.5–141.6. Neurologic impairment (modified NIS+7 [mNIS+7], NIS total score), disability (Rasch-built Overall Disability Scale [R-ODS]), gait speed (10-meter walk test [10-MWT]), grip strength, and QOL (Norfolk Quality of Life-Diabetic Neuropathy [Norfolk QOL-DN] questionnaire) were assessed.ResultsAcross all baseline NIS quartiles, patisiran improved several clinical markers of disease compared with placebo at 18 months. Patients in lower NIS quartiles, treated with patisiran earlier in the disease course, maintained better scores in mNIS+7, NIS total score, R-ODS, 10-MWT, grip strength, and Norfolk QOL-DN versus those in higher NIS quartiles, while placebo-treated patients experienced worsening of all functional measures after 18 months across all quartiles.ConclusionsPatisiran treatment improved neurologic function and QOL across a wide range of baseline polyneuropathy severities versus placebo. Timing of treatment initiation in patients with ATTRv amyloidosis remains critical for the preservation of function.(ClinicalTrials.gov number, NCT01960348)