PDF(Pubmed)
Abstract：
BACKGROUND: Transthyretin amyloidosis (ATTR) is a progressive, heterogeneous rare disease manifesting as ATTR polyneuropathy (ATTR-PN), ATTR cardiomyopathy (ATTR-CM), or a mixed phenotype. Tafamidis meglumine (20 mg po qd) is approved in some markets to delay neurologic progression in ATTR-PN, while high-dose tafamidis (80/61 mg po qd) is approved worldwide to reduce cardiovascular mortality and cardiovascular-related hospitalization in ATTR-CM. The objective of this study was to assess the real-world benefit of high-dose tafamidis for delaying neurologic progression in patients with mixed-phenotype variant ATTR-CM (ATTRv-CM).
METHODS: This exploratory, retrospective, observational cohort study evaluated anonymized electronic medical records and included adult patients with mixed-phenotype ATTRv-CM treated with high-dose tafamidis for at least 6 months. Neurologic assessments included the Medical Research Council (MRC) Scale for Muscle Strength, Neuropathy Impairment Score (NIS) muscle weakness subscale, and Polyneuropathy Disability (PND) instrument. Modified body mass index (mBMI) was also assessed.
RESULTS: Patients (N = 10) started tafamidis treatment an average of 3.8 months after diagnosis, with an average treatment duration of 20.8 months. Seven of 10 patients demonstrated normal muscle strength on the MRC scale throughout the study, and 9 of 10 patients had no decline in muscle strength during the post-treatment period. The NIS muscle weakness subscale score was ≤ 60 for all patients in the study at all time points, suggesting normal function to mild impairment. Six of 10 patients had no change in walking capacity as measured by the PND instrument at pre- and post-assessments, while one-third of patients had a decrease in PND stage (signaling improvement) from pre- to post-assessment. mBMI remained relatively stable throughout the study.
CONCLUSIONS: This is the first real-world study to demonstrate the potential value of high-dose tafamidis for delaying neurologic disease progression in patients with mixed-phenotype ATTRv-CM. The findings underscore the importance of multidisciplinary assessment for patients with ATTR amyloidosis.
BACKGROUND: ClinicalTrials.gov: NCT05139680.
METHODS: This exploratory, retrospective, observational cohort study evaluated anonymized electronic medical records and included adult patients with mixed-phenotype ATTRv-CM treated with high-dose tafamidis for at least 6 months. Neurologic assessments included the Medical Research Council (MRC) Scale for Muscle Strength, Neuropathy Impairment Score (NIS) muscle weakness subscale, and Polyneuropathy Disability (PND) instrument. Modified body mass index (mBMI) was also assessed.
RESULTS: Patients (N = 10) started tafamidis treatment an average of 3.8 months after diagnosis, with an average treatment duration of 20.8 months. Seven of 10 patients demonstrated normal muscle strength on the MRC scale throughout the study, and 9 of 10 patients had no decline in muscle strength during the post-treatment period. The NIS muscle weakness subscale score was ≤ 60 for all patients in the study at all time points, suggesting normal function to mild impairment. Six of 10 patients had no change in walking capacity as measured by the PND instrument at pre- and post-assessments, while one-third of patients had a decrease in PND stage (signaling improvement) from pre- to post-assessment. mBMI remained relatively stable throughout the study.
CONCLUSIONS: This is the first real-world study to demonstrate the potential value of high-dose tafamidis for delaying neurologic disease progression in patients with mixed-phenotype ATTRv-CM. The findings underscore the importance of multidisciplinary assessment for patients with ATTR amyloidosis.
BACKGROUND: ClinicalTrials.gov: NCT05139680.
摘要：
背景：转甲状腺素蛋白淀粉样变性（ATTR）是一种进行性，表现为ATTR多发性神经病（ATTR-PN）的异质性罕见疾病，ATTR心肌病（ATTR-CM），或混合表型。Tafamidis葡甲胺（20mgpoqd）在某些市场被批准用于延迟ATTR-PN的神经系统进展，而在ATTR-CM中，高剂量tafamidis（80/61mgpoqd）被批准用于降低心血管死亡率和心血管相关住院率。这项研究的目的是评估高剂量tafamidis对延迟混合表型变异ATTR-CM（ATTRv-CM）患者神经系统进展的现实益处。
方法：这是探索性的，回顾性,观察性队列研究评估了匿名的电子病历,纳入了ATTRv-CM混合表型的成年患者,这些患者接受了至少6个月的高剂量tafamidis治疗.神经系统评估包括医学研究理事会（MRC）肌肉力量量表，神经病变损伤评分（NIS）肌无力分量表，和多发性神经病残疾（PND）仪器。还评估了改良的体重指数（mBMI）。
结果：患者（N=10）在诊断后平均3.8个月开始塔法米米治疗，平均治疗时间为20.8个月。在整个研究中，10名患者中有7名在MRC量表上表现出正常的肌肉力量，10名患者中有9名在治疗后期间肌肉力量没有下降。研究中所有患者在所有时间点的NIS肌无力分量表评分均≤60，提示功能正常至轻度损害。10名患者中有6名患者在评估前和评估后通过PND仪器测量的步行能力没有变化。而三分之一的患者从评估前到评估后的PND分期(信号改善)降低.mBMI在整个研究过程中保持相对稳定。
结论：这是第一个真实的研究，以证明高剂量的他达米对延迟混合表型ATTRv-CM患者神经系统疾病进展的潜在价值。研究结果强调了多学科评估对ATTR淀粉样变性患者的重要性。
背景：ClinicalTrials.gov：NCT05139680。
方法：这是探索性的，回顾性,观察性队列研究评估了匿名的电子病历,纳入了ATTRv-CM混合表型的成年患者,这些患者接受了至少6个月的高剂量tafamidis治疗.神经系统评估包括医学研究理事会（MRC）肌肉力量量表，神经病变损伤评分（NIS）肌无力分量表，和多发性神经病残疾（PND）仪器。还评估了改良的体重指数（mBMI）。
结果：患者（N=10）在诊断后平均3.8个月开始塔法米米治疗，平均治疗时间为20.8个月。在整个研究中，10名患者中有7名在MRC量表上表现出正常的肌肉力量，10名患者中有9名在治疗后期间肌肉力量没有下降。研究中所有患者在所有时间点的NIS肌无力分量表评分均≤60，提示功能正常至轻度损害。10名患者中有6名患者在评估前和评估后通过PND仪器测量的步行能力没有变化。而三分之一的患者从评估前到评估后的PND分期(信号改善)降低.mBMI在整个研究过程中保持相对稳定。
结论：这是第一个真实的研究，以证明高剂量的他达米对延迟混合表型ATTRv-CM患者神经系统疾病进展的潜在价值。研究结果强调了多学科评估对ATTR淀粉样变性患者的重要性。
背景：ClinicalTrials.gov：NCT05139680。
