Huppke Brenda, Ellenberger David, Hummel Hannah, Stark Wiebke, Röbl Markus, Gärtner Jutta, Huppke Peter
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen, Georg August University Göttingen, Göttingen, Germany.
Department of Medical Statistics, University Medical Center Göttingen, Georg August University Göttingen, Göttingen, Germany.
JAMA Neurol. 2019 Oct 1;76(10):1157-1165. doi: 10.1001/jamaneurol.2019.1997.
Obesity reportedly increases the risk of pediatric multiple sclerosis (MS), but little is known about its association with disease course.
To investigate the association of obesity with pediatric MS risk and with first-line therapy response among children with MS.
DESIGN, SETTING, AND PARTICIPANTS: This single-center retrospective study used the medical records and database at the Center for MS in Childhood and Adolescence, Göttingen, Germany. The study included 453 patients with relapsing-remitting pediatric MS and body mass index (BMI) measurement taken within 6 months of diagnosis. Onset of the disease occurred between April 28, 1990, and June 26, 2016, and the mean disease duration was 38.4 months. Data were collected from July 14, 2016, to December 18, 2017.
Data on BMIs were stratified by sex and age using German BMI references and compared with the BMI data of 14 747 controls from a nationwide child health survey for odds ratio (OR) estimates. Baseline magnetic resonance imaging findings, intervals between first and second MS attacks, annualized relapse rates before and during treatment with interferon beta-1a or -1b and glatiramer acetate, frequency of second-line treatment, and Expanded Disability Status Scale (EDSS) scores were compared between nonoverweight (BMI≤90th percentile), overweight (BMI>90th-97th percentile), and obese (BMI>97th percentile) patients.
In total, 453 patients with pediatric MS were included, of whom 306 (67.5%) were female, and the mean (SD) age at diagnosis was 13.7 (2.7) years. At diagnosis, 126 patients (27.8%) were overweight or obese, with obesity associated with statistically significant twofold odds of MS in both sexes (girls OR, 2.19; 95% CI, 1.5-3.1; P < .001 vs boys OR, 2.14; 95% CI, 1.3-3.5; P = .003). Obese patients, compared with nonoverweight patients, had statistically significantly more relapses on first-line treatment with interferon beta and glatiramer acetate (ARR, 1.29 vs 0.72; P < .001) and a higher rate of second-line treatment (21 [56.8%] of 37 vs 48 [38.7%] of 124; P = .06). Baseline neuroimaging, interval between first and second MS attacks, pretreatment relapses, and EDSS progression scores were not correlated with BMI.
In this study, increased pediatric MS risk appeared to be associated with obesity, and obese patients did not respond well to first-line medications; altered pharmacokinetics appeared to be most likely factors in treatment response, suggesting that achieving healthy weight or adjusting the dose according to BMI could improve therapy response.
据报道,肥胖会增加儿童多发性硬化症(MS)的风险,但关于其与疾病病程的关联却知之甚少。
探讨肥胖与儿童MS风险以及MS患儿一线治疗反应之间的关联。
设计、地点和参与者:这项单中心回顾性研究使用了德国哥廷根儿童和青少年MS中心的病历和数据库。该研究纳入了453例复发缓解型儿童MS患者,并在诊断后6个月内测量了体重指数(BMI)。疾病发作时间为1990年4月28日至2016年6月26日,平均病程为38.4个月。数据收集时间为2016年7月14日至2017年12月18日。
使用德国BMI参考标准按性别和年龄对BMI数据进行分层,并与来自全国儿童健康调查的14747名对照的BMI数据进行比较,以估计比值比(OR)。比较了非超重(BMI≤第90百分位数)、超重(BMI>第90 - 97百分位数)和肥胖(BMI>第97百分位数)患者的基线磁共振成像结果、首次和第二次MS发作之间的间隔、使用干扰素β-1a或-1b以及醋酸格拉替雷治疗前和治疗期间的年化复发率、二线治疗频率和扩展残疾状态量表(EDSS)评分。
总共纳入了453例儿童MS患者,其中306例(67.5%)为女性,诊断时的平均(标准差)年龄为13.7(2.7)岁。诊断时,126例患者(27.8%)超重或肥胖,肥胖与男女MS的统计学显著两倍几率相关(女孩OR为2.19;95%CI为1.5 - 3.1;P <.001,男孩OR为2.14;95%CI为1.3 - 3.5;P = 0.003)。与非超重患者相比,肥胖患者在使用干扰素β和醋酸格拉替雷进行一线治疗时复发统计学上显著更多(年化复发率,1.29对0.72;P <.001),二线治疗率更高(37例中的21例[56.8%]对124例中的48例[38.7%];P = 0.06)。基线神经影像学、首次和第二次MS发作之间的间隔、治疗前复发和EDSS进展评分与BMI无关。
在本研究中,儿童MS风险增加似乎与肥胖有关,肥胖患者对一线药物反应不佳;药代动力学改变似乎是治疗反应的最可能因素,这表明实现健康体重或根据BMI调整剂量可能会改善治疗反应。