背景:改善和维持延髓功能是脊髓性肌萎缩症(SMA)疾病改善治疗的目标。缺乏标准化措施和广泛接受的球功能定义代表了SMA护理中的差距。
目标:一个多学科小组对一个阶段I(START)和两个阶段III(STR1VE-US,STR1VE-EU)研究,以定义和评估接受一次性基因替代疗法后1型SMA婴儿的球功能,阿贝帕沃维奇。
方法:我们将延髓功能定义为满足营养需求,同时保持气道保护和口头交流的能力。四个终点代表足够的球功能:(1)没有临床医生确定的生理性吞咽障碍,(2)接受充分的口服营养,(3)无表明肺不稳定的不良事件,以及(4)发声至少两种不同的能力,不同的元音。我们描述性地评估了达到每个终点和所有四个终点的患者的数量/百分比。患者随访至18个月大(STR1VE-US和STR1VE-EU)或输注后24个月(START)。
结果:总体而言,65例患者进行吞咽分析,营养摄入,和不良事件,和20个进行了沟通分析。在研究结束时,92%(60/65)的患者吞咽正常,75%(49/65)实现了完全的口服营养,92%(60/65)没有肺部不稳定的证据,95%(19/20)满足了通信端点,75%(15/20)实现了复合终点中的所有四个延髓功能分量。
结论:在这三个临床试验中,接受asemnogeneabeparvovec治疗的SMA1型患者达到并维持了本研究中使用的球功能标准.
BACKGROUND: Improvement and maintenance of bulbar function are goals of disease-modifying treatments for spinal muscular atrophy (SMA). Lack of standardized measures and a widely accepted definition of bulbar function represents a gap in SMA care.
OBJECTIVE: A multidisciplinary team conducted post-hoc analyses of pooled data from one phase 1 (START) and two phase 3 (STR1VE-US, STR1VE-EU) studies to define and evaluate bulbar function of infants with SMA type 1 after receiving one-time gene replacement therapy, onasemnogene abeparvovec.
METHODS: We defined bulbar function as the ability to meet nutritional needs while maintaining airway protection and the ability to communicate verbally. Four endpoints represented adequate bulbar function: (1) absence of clinician-identified physiologic swallowing impairment, (2) receiving full oral nutrition, (3) absence of adverse events indicating pulmonary instability, and (4) the ability to vocalize at least two different, distinct vowel sounds. We descriptively assessed numbers/percentages of patients who achieved each endpoint and all four collectively. Patients were followed until 18 months old (STR1VE-US and STR1VE-EU) or 24 months (START) post-infusion.
RESULTS: Overall, 65 patients were analyzed for swallowing, nutrition intake, and adverse events, and 20 were analyzed for communication. At study end, 92% (60/65) of patients had a normal swallow, 75% (49/65) achieved full oral nutrition, 92% (60/65) had no evidence of pulmonary instability, 95% (19/20) met the communication endpoint, and 75% (15/20) achieved all four bulbar function components in the composite endpoint.
CONCLUSIONS: In these three clinical trials, patients with SMA type 1 who received onasemnogene abeparvovec achieved and maintained the bulbar function criteria utilized within this investigation.