Objectives: To investigate the clinical efficacy and safety of salbutamol in the treatment of children with later-onset spinal muscular atrophy (SMA).
Methods: This study is a prospective single-arm phase Ⅲ clinical study. Pediatric patients with SMA type Ⅱ and Ⅲ who visited Department of Neurology, Children's Hospital, Zhejiang University School of Medicine from December 2020 to June 2022 were enrolled. All patients were evaluated with motor function scales, pulmonary function test and drug safety before study. Patients were treated with salbutamol tablets orally, with an initial dose of 1 mg (tid). If tolerable, the dose was increased to 1.5 mg (tid) in the second week, then increased to 2 mg (tid) from the third week and maintained for 6 months. Patients were followed up at 1, 3 and 6 months of treatment.
Results: Twenty-six patients were enrolled, including 10 boys and 16 girls. There were 16 cases of SMA type Ⅱ and 10 cases of type Ⅲ with age at treatment initiation of 5.67 (3.13, 7.02) years and disease duration of 2.54 (1.31, 4.71) years. The Hammersmith Functional Motor Scale-Expanded (HFMSE) scores were increased from 14.0 (6.5, 43.0) before treatment to 26.0 (15.0, 46.5) after treatment (Z=－4.144, P<0.01) in 25 cases. The Revised Upper Limb Module Scale scores were increased from 33.0 (25.5, 36.0) before treatment to 35.0 (31.0, 36.5) after treatment (Z=－2.214, P<0.05) in 9 cases. In 7 ambulant children with SMA type Ⅲ, the six minutes walking distance was increased by 30 (15, 52) m after a 6-month treatment (Z=－2.366, P<0.05). Compared with the baseline pulmonary functions the patients showed a significant increase in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) in 15 cases after treatment (all P<0.05). According to patients and caregivers subjective reporting, there were various degrees of improvement in coughing, sputum production ability and exercise endurance. No serious adverse events were observed during the study.
Conclusions: Short-term oral administration of salbutamol may improve motor and pulmonary functions in later-onset SMA children with good safety.
目的: 研究硫酸沙丁胺醇治疗晚发型脊髓性肌萎缩症（SMA）患儿的临床疗效和安全性。方法: 本研究为前瞻性单臂Ⅲ期临床研究。收集2020年12月—2022年6月就诊于浙江大学医学院附属儿童医院神经内科的SMA患儿。患儿入组前均完成运动功能量表评估、肺功能检查及用药安全性评估。所有入组的患儿均口服硫酸沙丁胺醇片，初始剂量为每次1 mg，每日三次；口服1周后如可耐受，第2周剂量增加至每次1.5 mg，每日三次；以此剂量口服1周后如患儿仍可耐受，在治疗第3周起增量至每次2 mg，每日三次维持直至治疗6个月。患儿分别于治疗1、3、6个月时门诊随访。结果: 26例患儿入组随访队列，男性10例，女性16例，SMA Ⅱ型16例，Ⅲ型10例，起始治疗年龄5.67（3.13，7.02）岁，病程2.54（1.31，4.71）年。25例患儿基线和硫酸沙丁胺醇治疗6个月后运动功能汉默史密斯功能运动扩展量表（HFMSE）评分为14.0（6.5，43.0）和26.0（15.0，46.5）分（Z=－4.144，P<0.01）；9例患儿基线和治疗6个月后修订版上肢模块量表评分为33.0（25.5，36.0）和35.0（31.0，36.5）分（Z=－2.214，P<0.05）；7例可独走Ⅲ型患儿治疗6个月时六分钟步行试验步行距离较基线增加30（15，52）m，相比基线显著提升（Z=－2.366，P<0.05）。治疗6个月后，患儿用力肺活量、第1秒用力呼气容积和呼气流量峰值较基线显著提升（均P<0.05）。患儿及照护者主观报告咳嗽咳痰能力、运动耐力等不同程度改善，且治疗随访期间未报告严重不良事件。结论: 短期口服硫酸沙丁胺醇有助于改善晚发型SMA患儿的运动功能及肺功能，安全性良好。.
Keywords: Drug therapy; Motor function; Pulmonary function; Salbutamol; Spinal muscular atrophy.