Abstract：
BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by homozygous deletion or loss-of-function mutations of the survival of motor neuron 1 (SMN1) gene, resulting in reduced levels of SMN protein throughout the body. Patients with SMA may have multiple tissue defects, which could present prior to neuromuscular symptoms.
OBJECTIVE: To assess the signs, comorbidities and potential extraneural manifestations associated with SMA in treatment-naïve patients.
METHODS: This observational, retrospective and matched-cohort study used secondary insurance claims data from the US IBM® MarketScan® Commercial, Medicaid and Medicare Supplemental databases between 01/01/2000 and 12/31/2013. Treatment-naïve individuals aged≤65 years with≥2 International Classification of Diseases, Ninth Revision (ICD-9) SMA codes were stratified into four groups (A-D), according to age at index (date of first SMA code recorded) and type of ICD-9 code used, and matched with non-SMA controls. The occurrence of ICD-9 codes, which were converted to various classifications (phecodes and system classes), were compared between groups in pre- and post-index periods.
RESULTS: A total of 1,457 individuals with SMA were included and matched to 13,362 controls. Increasing numbers of SMA-associated phecodes and system classes were generally observed from pre- to post-index across all groups. The strongest associations were observed in the post-index period for the youngest age groups. Endocrine/metabolic disorders were associated with SMA in almost all groups and across time periods.
CONCLUSIONS: This exploratory study confirmed the considerable disease burden in patients with SMA and identified 305 unique phecodes associated with SMA, providing a rationale for further research into the natural history and progression of SMA, including extraneural manifestations of the disease.
OBJECTIVE: To assess the signs, comorbidities and potential extraneural manifestations associated with SMA in treatment-naïve patients.
METHODS: This observational, retrospective and matched-cohort study used secondary insurance claims data from the US IBM® MarketScan® Commercial, Medicaid and Medicare Supplemental databases between 01/01/2000 and 12/31/2013. Treatment-naïve individuals aged≤65 years with≥2 International Classification of Diseases, Ninth Revision (ICD-9) SMA codes were stratified into four groups (A-D), according to age at index (date of first SMA code recorded) and type of ICD-9 code used, and matched with non-SMA controls. The occurrence of ICD-9 codes, which were converted to various classifications (phecodes and system classes), were compared between groups in pre- and post-index periods.
RESULTS: A total of 1,457 individuals with SMA were included and matched to 13,362 controls. Increasing numbers of SMA-associated phecodes and system classes were generally observed from pre- to post-index across all groups. The strongest associations were observed in the post-index period for the youngest age groups. Endocrine/metabolic disorders were associated with SMA in almost all groups and across time periods.
CONCLUSIONS: This exploratory study confirmed the considerable disease burden in patients with SMA and identified 305 unique phecodes associated with SMA, providing a rationale for further research into the natural history and progression of SMA, including extraneural manifestations of the disease.
摘要：
背景：脊髓性肌萎缩症（SMA）是由运动神经元1（SMN1）基因的存活纯合子缺失或功能丧失突变引起的神经肌肉疾病，导致整个身体的SMN蛋白水平降低。SMA患者可能有多个组织缺损,这可能在神经肌肉症状之前出现。
目的：为了评估体征，初治患者与SMA相关的合并症和潜在的神经外表现。
方法：这种观察，回顾性和配对队列研究使用了来自美国IBM®MarketScan®Commercial的二级保险索赔数据，2000年1月1日至2013年12月31日之间的Medicaid和Medicare补充数据库。年龄≤65岁，≥2种国际疾病分类的未治疗个体，第九次修订(ICD-9)SMA代码分为四组(A-D)，根据指数年龄（记录的第一个SMA代码的日期）和使用的ICD-9代码的类型，并与非SMA控件匹配。ICD-9代码的出现，它们被转换为各种分类(音码和系统类)，在指数前和指数后的组间进行了比较。
结果：共纳入1,457名SMA患者，并与13,362名对照相匹配。在所有组中，从指数前到指数后，通常观察到SMA相关的音码和系统类别的数量都在增加。对于最年轻的年龄组，在索引后时期观察到最强的关联。内分泌/代谢紊乱在几乎所有组和不同时间段都与SMA相关。
结论：这项探索性研究证实了SMA患者的巨大疾病负担，并确定了305种与SMA相关的独特特征，为进一步研究SMA的自然历史和发展提供了理论基础，包括疾病的神经外表现。
目的：为了评估体征，初治患者与SMA相关的合并症和潜在的神经外表现。
方法：这种观察，回顾性和配对队列研究使用了来自美国IBM®MarketScan®Commercial的二级保险索赔数据，2000年1月1日至2013年12月31日之间的Medicaid和Medicare补充数据库。年龄≤65岁，≥2种国际疾病分类的未治疗个体，第九次修订(ICD-9)SMA代码分为四组(A-D)，根据指数年龄（记录的第一个SMA代码的日期）和使用的ICD-9代码的类型，并与非SMA控件匹配。ICD-9代码的出现，它们被转换为各种分类(音码和系统类)，在指数前和指数后的组间进行了比较。
结果：共纳入1,457名SMA患者，并与13,362名对照相匹配。在所有组中，从指数前到指数后，通常观察到SMA相关的音码和系统类别的数量都在增加。对于最年轻的年龄组，在索引后时期观察到最强的关联。内分泌/代谢紊乱在几乎所有组和不同时间段都与SMA相关。
结论：这项探索性研究证实了SMA患者的巨大疾病负担，并确定了305种与SMA相关的独特特征，为进一步研究SMA的自然历史和发展提供了理论基础，包括疾病的神经外表现。
