Long-term treatment with leuprorelin for spinal and bulbar muscular atrophy: natural history-controlled study
Long-term treatment with leuprorelin for spinal and bulbar muscular atrophy: natural history-controlled study
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DOI：
10.1136/jnnp-2017-316015
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发表时间：
2017-12-01
影响因子：
11
通讯作者：
Sobue, Gen
中科院分区：
文献类型：
--
作者：
Hashizume, Atsushi;Katsuno, Masahisa;Sobue, Gen
目的 评估脊髓和延髓性肌萎缩症 (SBMA) 的预后和进展，这是一种罕见的 X 连锁运动神经元疾病，由 AR（雄激素受体）基因中的三核苷酸重复扩增引起，经醋酸亮丙瑞林治疗长期雄激素抑制后。 方法 在本自然史对照研究中，36 例 SBMA 患者接受醋酸亮丙瑞林治疗长达 84 个月（醋酸亮丙瑞林治疗组；LT 组）和对 29 名未接受特殊治疗的 SBMA 患者（未治疗组；NT 组）进行了分析。使用修订版肌萎缩侧索硬化症功能评定量表（ALSFRS-R）和修订版 Norris 评分，通过运动功能的纵向定量评估来评估疾病进展。此外，我们选择了两个主要的临床终点事件，即需要住院治疗的肺炎和死亡的发生，来评估长期醋酸亮丙瑞林治疗后的疾病预后。结果在我们使用随机斜率模型对纵向疾病进展进行分析时，我们观察到 ALSFRS-R 总分、Limb Norris 评分和 Norris Bulbar 评分与 LT 组存在显着差异（分别为 p=0.005、0.026 和 0.020）。与 NT 组相比，每 12 个月的下降速度较慢。就事件分析而言，就无事件生存期而言，LT 组的预后优于 NT 组 (p=0.021)。 结论 长期使用醋酸亮丙瑞林治疗似乎可以延缓 SBMA 受试者的功能衰退并抑制肺炎和死亡的发生率。
Objective To evaluate the prognosis and progression of spinal and bulbar muscular atrophy (SBMA), a rare X-linked motor neuron disorder caused by trinucleotide repeat expansion in the AR (androgen receptor) gene, after long-term androgen suppression with leuprorelin acetate treatment.Methods In the present natural history-controlled study, 36 patients with SBMA treated with leuprorelin acetate for up to 84 months (leuprorelin acetate-treated group; LT group) and 29 patients with SBMA with no specific treatment (non-treated group; NT group) were analysed. Disease progression was evaluated by longitudinal quantitative assessment of motor functioning using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and the modified Norris score. In addition, we selected two major clinical endpoint events, namely the occurrence of pneumonia requiring hospitalisation and death, to evaluate disease prognosis following long-term leuprorelin acetate treatment.Results In our analysis of the longitudinal disease progression using the random slope model, we observed a significant difference in the ALSFRS-R total score, the Limb Norris Score, and the Norris Bulbar Score (p=0.005, 0.026 and 0.020, respectively), with the LT group exhibiting a slower per-12-months decline compared with the NT group. As for the event analysis, the prognosis of the LT group was better in comparison to the NT group as for the event-free survival period (p=0.021).Conclusion Long-term treatment with leuprorelin acetate appears to delay the functional decline and suppress the incidence of pneumonia and death in subjects with SBMA.