Unidade Clinica de Paramiloidose, Hospital de Santo António, Largo Prof Abel Salazar, 4099-001, Porto, Portugal,
J Neurol. 2013 Nov;260(11):2802-14. doi: 10.1007/s00415-013-7051-7. Epub 2013 Aug 22.
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.
他替昔单抗是一种转甲状腺素蛋白（TTR）的动力学稳定剂，在一项为期 18 个月的随机对照试验（研究 Fx-005）中，延缓了 Val30Met 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评估了替昔单抗 20mg 每日一次的长期安全性、耐受性和疗效，共纳入 86 例先前接受替昔单抗或安慰剂治疗的患者。疗效评估包括下肢神经病损伤评分（NIS-LL）、诺福克生活质量-糖尿病神经病总体生活质量（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 稳定的每月变化率，并监测了不良事件（AE）。继续使用替昔单抗的患者的 NIS-LL（从 0.08 到 0.11/月；p=0.60）和 TQOL（从-0.03 到 0.25；p=0.16）的变化率保持稳定。从安慰剂转换的患者的 NIS-LL 每月变化率下降（从 0.34 到 0.16/月；p=0.01），TQOL 评分也下降（从 0.61 到-0.16；p<0.001）。接受替昔单抗治疗 30 个月的患者，其神经功能的保存率比后期开始替昔单抗治疗的患者高 55.9%，这一结果通过 NIS-LL 进行评估。接受替昔单抗治疗 30 个月的患者中有 94.1%的血浆 TTR 得到稳定。两组的不良事件相似；没有患者因不良事件而停药。长期替昔单抗治疗耐受性良好，30 个月内神经功能恶化的速度得以持续减缓。替昔单抗还减缓了先前接受安慰剂治疗的患者的神经损伤，但当替昔单抗更早开始使用时，治疗益处更大。
