Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy.
Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy.
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DOI：
10.1007/s00415-013-7051-7
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发表时间：
2013-11
影响因子：
6
通讯作者：
Grogan DR
中科院分区：
文献类型：
--
作者：
Coelho T;Maia LF;da Silva AM;Cruz MW;Planté-Bordeneuve V;Suhr OB;Conceiçao I;Schmidt HH;Trigo P;Kelly JW;Labaudinière R;Chan J;Packman J;Grogan DR
在一项为期18个月的随机对照试验（研究Fx-005）中，Tafamidis是一种甲状腺素运载蛋白（TTR）动力学稳定剂，可延迟Val 30 Met TTR家族性淀粉样多发性神经病（TTR-FAP）患者的神经病变进展。这项为期12个月的开放标签扩展研究在86名早期接受过tafamlitazone或安慰剂盲法治疗的患者中评估了tafamlitazone 20 mg每日一次的长期安全性、耐受性和疗效。疗效指标包括下肢神经病变损伤评分（NIS-LL）、诺福克生活质量-糖尿病神经病变总生活质量（TQOL）评分以及神经功能和营养状态的变化。我们量化了疗效指标和TTR稳定性的每月变化率，并监测了不良事件（AE）。继续接受他伐他汀治疗的患者的NIS-LL（从0.08至0.11/月; p = 0.60）和TQOL（从-0.03至0.25; p = 0.16）变化率稳定。在从安慰剂转换的患者中，NIS-LL的月变化率下降（从0.34降至0.16/月; p = 0.01），TQOL评分也是如此（从0.61降至-0.16; p < 0.001）。通过NIS-LL测量，接受他伐他汀治疗30个月的患者的神经功能保留率比随后开始接受他伐他汀治疗的患者高55.9%。在接受他伐他汀治疗30个月的患者中，94.1%的患者的血浆TTR稳定。两组间AE相似;无患者因AE而停药。长期使用他伐他汀耐受性良好，神经功能恶化率降低持续超过30个月。Tafamidis也减缓了以前服用安慰剂的患者的神经功能损害，但当tafamidis开始更早时，治疗效果更好。
Tafamidis, a transthyretin (TTR) kinetic stabilizer, delayed neuropathic progression in patients with Val30Met TTR familial amyloid polyneuropathy (TTR-FAP) in an 18-month randomized controlled trial (study Fx-005). This 12-month, open-label extension study evaluated the long-term safety, tolerability, and efficacy of tafamidis 20 mg once daily in 86 patients who earlier received blinded treatment with tafamidis or placebo. Efficacy measures included the Neuropathy Impairment Score in the Lower Limbs (NIS-LL), Norfolk Quality of Life-Diabetic Neuropathy total quality of life (TQOL) score, and changes in neurologic function and nutritional status. We quantified the monthly rates of change in efficacy measures, and TTR stabilization, and monitored adverse events (AEs). Patients who continued on tafamidis had stable rates of change in NIS-LL (from 0.08 to 0.11/month; p = 0.60) and TQOL (from −0.03 to 0.25; p = 0.16). In patients switched from placebo, the monthly rate of change in NIS-LL declined (from 0.34 to 0.16/month; p = 0.01), as did TQOL score (from 0.61 to −0.16; p < 0.001). Patients treated with tafamidis for 30 months had 55.9 % greater preservation of neurologic function as measured by the NIS-LL than patients in whom tafamidis was initiated later. Plasma TTR was stabilized in 94.1 % of patients treated with tafamidis for 30 months. AEs were similar between groups; no patients discontinued because of an AE. Long-term tafamidis was well tolerated, with the reduced rate of neurologic deterioration sustained over 30 months. Tafamidis also slowed neurologic impairment in patients previously given placebo, but treatment benefits were greater when tafamidis was begun earlier.
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DOI：
10.1073/pnas.1121005109
发表时间：
2012-06-12
影响因子：
11.1
作者：
Bulawa, Christine E.;Connelly, Stephen;Labaudiniere, Richard
通讯作者：
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