背景:Nusinersen临床试验对患有5q相关性脊髓性肌萎缩症(SMA)的青少年和成人的数据有限。我们进行了系统的文献综述(SLR)和荟萃分析,以评估nusinersen在青少年和成人SMA临床实践中的有效性。
方法:我们的搜索包括发表于2016年12月23日至2022年07月01日的论文,其中≥5名年龄≥13岁的个体,以及≥6个月的关于≥1个选定运动功能结果的数据[Hammersmith功能运动量表扩展(HFMSE),修改上肢模块(RULM)和六分钟步行测试(6MWT)]。对于荟萃分析,使用随机效应模型汇集效应大小.了解疾病严重程度的治疗效果,按SMA类型和动态进行亚组meta分析.
结果:14篇出版物,包括539名患者随访24个月,符合SLR的纳入标准。患者年龄为13-72岁,大多数(99%)患有II型或III型SMA。在组水平上始终观察到运动功能的适度改善或稳定性。在HFMSE中观察到自基线的平均显著增加[2.3分(95%CI1.3-3.3)],其中32.1%(21.7-44.6)的患者在18个月时表现出临床意义的增加(≥3分)。始终发现RULM显着增加,在14个月时,平均增加1.1分(0.7-1.4)和38.3%(30.3-47.1),显示有临床意义的改善(≥2分)。在非卧床病人中,在14个月时,平均6MWT距离显著增加,为25.0m(8.9~41.2),50.9%(33.4~68.2)显示有临床意义的改善(≥30m).对于受影响较小的患者,HFMSE的增加更大,而受影响更严重的患者表现出更大的RULM改善。
结论:研究结果提供了巩固的证据,证明nusinersen可有效改善或稳定许多患有广泛SMA的青少年和成年人的运动功能。
运动神经元是大脑和脊髓中控制肌肉功能的特化细胞。患有脊髓性肌萎缩症(SMA)的人没有足够的存活运动神经元(SMN)蛋白,哪些运动神经元需要发挥作用。因此,患有SMA的人经历肌肉功能下降,随着时间的推移变得更糟。Nusinersen是一种增加大脑和脊髓中SMN蛋白含量的药物。然而,nusinersen的大多数临床试验是在患有SMA的婴儿和儿童中进行的.关于nusinersen在患有SMA的青少年和成年人中的影响知之甚少,这些人可能患有不太严重但仍在进行性的疾病。在这份手稿中,我们首先对研究人员发表的研究进行了全面回顾和分析,这些研究人员用nusinersen治疗青少年和成人长达24个月.然后我们使用了额外的分析,称为荟萃分析,这让我们能够结合几篇文章中的信息,这样我们就能更好地了解nusinersen是否帮助了这些病人.我们查看了研究人员用来观察nusinersen如何影响患者运动功能的3项测试。Hammersmith功能性运动量表(HFMSE)评估上肢和下肢运动功能;修订的上肢模块(RULM)评估上肢功能;六分钟步行测试(6MWT)测量一个人在6分钟内可以行走的最大距离。我们的研究表明,在许多患有SMA的青少年和成年人中,nusinersen可以改善运动功能或防止运动功能恶化。
BACKGROUND: Nusinersen clinical trials have limited data on adolescents and adults with 5q-associated spinal muscular atrophy (SMA). We conducted a systematic literature review (SLR) and meta-analysis to assess effectiveness of
nusinersen in adolescents and adults with SMA in clinical practice.
METHODS: Our search included papers published 12/23/2016 through 07/01/2022 with ≥ 5 individuals ≥ 13 years of age and with ≥ 6 months\' data on ≥ 1 selected motor function outcomes [Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), and Six-Minute Walk Test (6MWT)]. For meta-analysis, effect sizes were pooled using random-effects models. To understand treatment effects by disease severity, subgroup meta-analysis by SMA type and ambulatory status was conducted.
RESULTS: Fourteen publications including 539 patients followed up to 24 months met inclusion criteria for the SLR. Patients were age 13-72 years and most (99%) had SMA Type II or III. Modest improvement or stability in motor function was consistently observed at the group level. Significant mean increases from baseline were observed in HFMSE [2.3 points (95% CI 1.3-3.3)] with 32.1% (21.7-44.6) of patients demonstrating a clinically meaningful increase (≥ 3 points) at 18 months. Significant increases in RULM were consistently found, with a mean increase of 1.1 points (0.7-1.4) and 38.3% (30.3-47.1) showing a clinically meaningful improvement (≥ 2 points) at 14 months. Among ambulatory patients, there was a significant increase in mean 6MWT distance of 25.0 m (8.9-41.2) with 50.9% (33.4-68.2) demonstrating a clinically meaningful improvement (≥ 30 m) at 14 months. The increases in HFMSE were greater for less severely affected patients, whereas more severely affected patients showed greater improvement in RULM.
CONCLUSIONS: Findings provide consolidated evidence that nusinersen is effective in improving or stabilizing motor function in many adolescents and adults with a broad spectrum of SMA.
Motor neurons are specialized cells in the brain and spinal cord that control the function of muscles. People with spinal muscular atrophy (SMA) do not make enough survival motor neuron (SMN) protein, which motor neurons need to function. As a result, people with SMA experience decreased muscle function that gets worse over time.
Nusinersen is a drug that increases the amount of SMN protein made in the brain and spinal cord. However, most clinical trials of
nusinersen have been in infants and children with SMA. Less is known about the effects of nusinersen in teenagers and adults with SMA who may have less severe but still progressive forms of the disease. In this manuscript, we first conducted a thorough review and analysis of research published by investigators who treated teenagers and adults with nusinersen for up to 24 months. We then used an additional analysis, called a meta-analysis, that allowed us to combine the information from several articles, so that we could better understand whether nusinersen helped these patients. We looked at 3 tests that investigators used to see how
nusinersen affected patients’ motor function. The Hammersmith Functional Motor Scale–Expanded (HFMSE) assesses upper and lower limb motor function; the Revised Upper Limb Module (RULM) evaluates upper limb function; and the Six-Minute Walk Test (6MWT) measures the maximum distance a person can walk in 6 minutes. Our study showed that nusinersen can improve motor function or prevent motor function from getting worse in many teenagers and adults with SMA.