Is obesity associated with multiple sclerosis risk and response to first-line therapy in a pediatric population in Germany?
In this single-center study of 453 German children with a multiple sclerosis diagnosis, obesity was associated with twofold greater odds of the disease and more frequent failure of first-line treatment with interferon beta-1a or 1b and glatiramer acetate, thereby increasing the number of patients on second-line treatment.
Obesity appeared to be statistically significantly associated with increased risk of pediatric multiple sclerosis and with worse treatment response to first-line treatment; a healthy weight may potentially optimize treatment outcomes and reduce the disease burden and costs.
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.
Main Outcomes and Measures
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.
Conclusions and Relevance
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.
Huppke B, Ellenberger D, Hummel H, et al. Association of Obesity With Multiple Sclerosis Risk and Response to First-line Disease Modifying Drugs in Children. JAMA Neurol. Published online July 15, 2019. doi:10.1001/jamaneurol.2019.1997
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