诺西那生钠在1型和2型脊髓性肌萎缩症青少年及成年患者中的长期疗效及其评估

Long-term efficacy of nusinersen and its evaluation in adolescent and adult patients with spinal muscular atrophy types 1 and 2.

作者信息

Iwayama Hideyuki, Kawahara Kohei, Takagi Mizuki, Numoto Shingo, Azuma Yoshiteru, Kurahashi Hirokazu, Yasue Yumiko, Kawajiri Hiroyuki, Yanase Atsushi, Ito Teruyoshi, Kimura Shinya, Kumagai Toshiyuki, Okumura Akihisa

机构信息

Department of Pediatrics, Aichi Medical University School of Medicine, Nagakute, Japan.

出版信息

Brain Dev. 2023 Feb;45(2):110-116. doi: 10.1016/j.braindev.2022.10.006. Epub 2022 Nov 2.

DOI:10.1016/j.braindev.2022.10.006

PMID:36335004

Abstract

BACKGROUNDS

The efficacy of nusinersen and its evaluation in patients with spinal muscular atrophy (SMA) has been established in clinical trials only for pediatric patients, not for adolescent and adult patients who developed SMA in infancy or early childhood. We report a long-term follow-up in adolescent and adult patients with SMA types 1 and 2.

METHODS

Nusinersen-treated patients with SMA types 1 and 2 between 2017 and 2022 were retrospectively reviewed. We compared baseline motor function tests with those after the final treatment. Physical and occupational therapists performed Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Functional Motor Scale-Expanded (HFMSE), and Revised Upper Limb Module (RULM). The Landau and Galant reflexes were not performed in CHOP-INTEND. Meaningful improvement was defined as CHOP-INTEND, 4; HFSME, 3; and RULM, 2.

RESULTS

Seven patients with SMA (type 1, 1; type 2, 6) with a median age of 23 (range, 12-40)years were treated with nusinersen for 3.55 (1.78-4.53)years. Improvement was detected in CHOP-INTEND (pre, 5 [0-31]; post, 21 [0-39]; difference, 5 [0-26]; p = 0.100) without significance, although not in HFMSE (pre, 0 [0-3]; post, 0 [0-5]; difference, 0 [0-2]; p = 0.346) and RULM (pre, 1 [0-20]; post, 3 [0-21]; difference, 1 [0-2]; p = 0.089). Owing to prolonged treatment intervals with the COVID-19 pandemic, RULM worsened in two patients.

CONCLUSION

Nusinersen was effective in long-term follow-up. Only CHOP-INTEND showed meaningful improvement. The interval between doses of nusinersen should not be prolonged even with the COVID-19 pandemic.

摘要

背景

在临床试验中，仅确定了诺西那生钠对脊髓性肌萎缩症（SMA）患儿的疗效及其评估，对于在婴儿期或幼儿期患SMA的青少年和成人患者尚未确定。我们报告了对1型和2型SMA青少年及成人患者的长期随访情况。

方法

对2017年至2022年间接受诺西那生钠治疗的1型和2型SMA患者进行回顾性研究。我们将基线运动功能测试结果与最后一次治疗后的结果进行了比较。物理治疗师和职业治疗师进行了费城儿童医院神经肌肉疾病婴儿测试（CHOP-INTEND）、哈默史密斯功能运动量表扩展版（HFMSE）和修订上肢模块（RULM）评估。CHOP-INTEND评估中未进行兰道反射和加兰特反射。有意义的改善定义为CHOP-INTEND评分为4分、HFSME评分为3分、RULM评分为2分。

结果

7例SMA患者（1型1例，2型6例），中位年龄23岁（范围12 - 40岁），接受诺西那生钠治疗3.55年（1.78 - 4.53年）。CHOP-INTEND评分有改善（治疗前5分[0 - 31分]，治疗后21分[0 - 39分]，差值5分[0 - 26分]；p = 0.100），但无统计学意义，HFMSE评分（治疗前0分[0 - 3分]，治疗后0分[0 - 5分]，差值0分[0 - 2分]；p = 0.346）和RULM评分（治疗前1分[0 - 20分]，治疗后3分[0 - 21分]，差值1分[0 - 2分]；p = 0.089）未改善。由于新冠疫情导致治疗间隔延长，2例患者的RULM评分恶化。