生存、运动功能和运动里程碑：AVXS-101 与 nusinersen 治疗 1 型脊髓性肌萎缩症婴儿的比较。
Survival, Motor Function, and Motor Milestones: Comparison of AVXS-101 Relative to Nusinersen for the Treatment of Infants with Spinal Muscular Atrophy Type 1.
机构信息
AveXis, Inc., Bannockburn, IL, USA.
Precision Xtract, Oakland, CA, USA.
出版信息
Adv Ther. 2019 May;36(5):1164-1176. doi: 10.1007/s12325-019-00923-8. Epub 2019 Mar 16.
INTRODUCTION
Infants with spinal muscular atrophy (SMA) type 1 typically face a decline in motor function and a severely shortened life expectancy. Clinical trials for SMA type 1 therapies, onasemnogene abeparvovec (AVXS-101) and nusinersen, demonstrated meaningful improvements in efficacy (e.g., overall survival) but there were no head-to-head clinical trials assessing comparative efficacy. This study estimated the treatment effects of AVXS-101 relative to nusinersen for the treatment of SMA type 1.
METHODS
Overall survival, event-free survival (no death or need to use permanent assisted ventilation), improvement in motor function [increase of ≥ 4 points in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score from baseline], and motor milestone achievements (head control, rolling over, and sitting unassisted) reported in the onasemnogene abeparvovec (AVXS-101-CL-101; NCT02122952) and nusinersen (ENDEAR; NCT02193074) clinical trials were indirectly compared using frequentist and Bayesian approaches.
RESULTS
Among symptomatic infants with SMA type 1, the number needed to treat (NNT) to prevent one more death with AVXS-101 instead of nusinersen was 6.2 [95% confidence intervals (CI) = 4.1-12.2], and the probability of preventing death was 20% higher for patients treated with AVXS-101 than nusinersen [risk ratio (RR) = 1.2, 95% CI 1.1-1.3]. For event-free survival, the NNT to prevent one more event was 2.6 (95% CI 2.0-3.6) and RR was 1.6 (95% CI 1.4-1.9). For improvement in motor function, NNT was 3.5 (95% CI 2.6-5.3) and RR was 1.4 (95% CI 1.2-1.6). For milestone achievements, the NNTs were 1.4 (95% CI 1.1-1.9), 1.5 (95% CI 1.1-2.5), and 1.2 (95% CI 1.0-1.5); RRs 4.2 (95% CI 2.6-6.7), 7.8 (95% CI 3.6-17.0), and 11.2 (95% CI 5.1-24.5) for head control, rolling over, and sitting unassisted, respectively. Results were similar using the Bayesian approach.
CONCLUSION
This indirect comparison (AVXS-101-CL-101 vs. ENDEAR) among symptomatic SMA type 1 infants suggests that AVXS-101 may have an efficacy advantage relative to nusinersen for overall survival, independence from permanent assisted ventilation, motor function, and motor milestones.
FUNDING
AveXis.
简介
患有脊髓性肌萎缩症（SMA）1 型的婴儿通常会出现运动功能下降和预期寿命显著缩短。SMA 1 型疗法的临床试验，onasemnogene abeparvovec（AVXS-101）和 nusinersen，显示出在疗效方面的显著改善（例如，总生存率），但没有头对头的临床试验来评估比较疗效。本研究估计了 AVXS-101 相对于 nusinersen 治疗 SMA 1 型的治疗效果。
方法
总体生存率、无事件生存率（无死亡或需要使用永久性辅助通气）、运动功能改善（费城儿童医院婴儿神经肌肉疾病测试（CHOP-INTEND）评分从基线增加≥4 分）和运动里程碑成就（头部控制、翻身和独坐）在 onasemnogene abeparvovec（AVXS-101-CL-101；NCT02122952）和 nusinersen（ENDEAR；NCT02193074）临床试验中进行了报告，并使用频率论和贝叶斯方法进行了间接比较。
结果
在患有 SMA 1 型的有症状婴儿中，用 AVXS-101 替代 nusinersen 预防一人死亡的所需治疗人数（NNT）为 6.2[95%置信区间（CI）=4.1-12.2]，用 AVXS-101 治疗的患者死亡概率比用 nusinersen 治疗的患者高 20%[风险比（RR）=1.2，95%CI=1.1-1.3]。对于无事件生存率，预防一次事件的 NNT 为 2.6（95%CI=2.0-3.6），RR 为 1.6（95%CI=1.4-1.9）。对于运动功能的改善，NNT 为 3.5（95%CI=2.6-5.3），RR 为 1.4（95%CI=1.2-1.6）。对于里程碑成就，NNTs 分别为 1.4（95%CI=1.1-1.9）、1.5（95%CI=1.1-2.5）和 1.2（95%CI=1.0-1.5）；RR 分别为 4.2（95%CI=2.6-6.7）、7.8（95%CI=3.6-17.0）和 11.2（95%CI=5.1-24.5），分别为头部控制、翻身和独坐。使用贝叶斯方法得到的结果相似。
结论
在患有 SMA 1 型的有症状婴儿中进行的这项间接比较（AVXS-101-CL-101 与 ENDEAR）表明，与 nusinersen 相比，AVXS-101 可能在总生存率、免于永久性辅助通气、运动功能和运动里程碑方面具有疗效优势。
资金来源
AveXis。
Zotero 插件