Fracture Risk Associated With Dimethyl Fumarate Treatment in Multiple Sclerosis Patients: Population Heterogeneity and Temporal Patterns

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-09-11 DOI:10.1111/cns.70612

Dongdong He, Jingkai Di, Peirui Jiang, Lujia Liu, Feida Wang, Chuan Xiang

{"title":"Fracture Risk Associated With Dimethyl Fumarate Treatment in Multiple Sclerosis Patients: Population Heterogeneity and Temporal Patterns","authors":"Dongdong He, Jingkai Di, Peirui Jiang, Lujia Liu, Feida Wang, Chuan Xiang","doi":"10.1111/cns.70612","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>Dimethyl fumarate (DMF) is currently recommended as a first-line therapy for multiple sclerosis (MS). Investigating its adverse events (AEs) holds significant clinical importance. This study aimed to explore the association between DMF and fracture-related AEs.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Data from the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q3 2024) were analyzed using disproportionality analysis. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM) were employed to identify and characterize AEs. Age- and gender-specific subgroup analyses were conducted to evaluate AE patterns. Additionally, Weibull distribution analysis was performed to assess the temporal relationship of AE onset.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Overall, spinal fusion fracture (ROR = 13.13, 95% CI: 1.73–99.86) and coccyx fracture (ROR = 3.05, 95% CI: 1.92–4.86) exhibited the strongest signals. Gender and age heterogeneity were observed in DMF-associated fracture risks. Female patients showed the highest signals for spinal fusion bone fracture (ROR = 13.13) and coccyx fracture (ROR = 2.80), while males predominantly exhibited patella (ROR = 4.94) and scapula fractures (ROR = 3.68). Age stratification revealed elevated risks of forearm fracture (ROR = 10.29, 95% CI: 4.24–24.96) and ankle fracture (ROR = 5.63, 95% CI: 4.32–7.35) in elderly patients, whereas younger populations displayed diverse multi-site fractures. Time-to-onset (TTO) analysis indicated that 63.62% of fractures occurred within the first 2 years of the treatment cycle, with a median onset time of 506 days. Weibull distribution modeling indicated that DMF's failure pattern aligned with an early failure-type curve.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>DMF use is associated with an increased risk of fracture-related AEs, with demographic variations in susceptibility. This study provides critical insights into the safety profile of DMF in MS management, underscoring the need for vigilance in high-risk populations.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70612","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS Neuroscience & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cns.70612","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

Dimethyl fumarate (DMF) is currently recommended as a first-line therapy for multiple sclerosis (MS). Investigating its adverse events (AEs) holds significant clinical importance. This study aimed to explore the association between DMF and fracture-related AEs.

Methods

Data from the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q3 2024) were analyzed using disproportionality analysis. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM) were employed to identify and characterize AEs. Age- and gender-specific subgroup analyses were conducted to evaluate AE patterns. Additionally, Weibull distribution analysis was performed to assess the temporal relationship of AE onset.

Results

Overall, spinal fusion fracture (ROR = 13.13, 95% CI: 1.73–99.86) and coccyx fracture (ROR = 3.05, 95% CI: 1.92–4.86) exhibited the strongest signals. Gender and age heterogeneity were observed in DMF-associated fracture risks. Female patients showed the highest signals for spinal fusion bone fracture (ROR = 13.13) and coccyx fracture (ROR = 2.80), while males predominantly exhibited patella (ROR = 4.94) and scapula fractures (ROR = 3.68). Age stratification revealed elevated risks of forearm fracture (ROR = 10.29, 95% CI: 4.24–24.96) and ankle fracture (ROR = 5.63, 95% CI: 4.32–7.35) in elderly patients, whereas younger populations displayed diverse multi-site fractures. Time-to-onset (TTO) analysis indicated that 63.62% of fractures occurred within the first 2 years of the treatment cycle, with a median onset time of 506 days. Weibull distribution modeling indicated that DMF's failure pattern aligned with an early failure-type curve.

Conclusion

DMF use is associated with an increased risk of fracture-related AEs, with demographic variations in susceptibility. This study provides critical insights into the safety profile of DMF in MS management, underscoring the need for vigilance in high-risk populations.

Abstract Image

查看原文本刊更多论文

多发性硬化症患者富马酸二甲酯治疗与骨折风险相关：人群异质性和时间模式

富马酸二甲酯（DMF）目前被推荐作为多发性硬化症（MS）的一线治疗药物。研究其不良事件（ae）具有重要的临床意义。本研究旨在探讨DMF与骨折相关ae之间的关系。方法对FDA不良事件报告系统（FAERS）数据库2004年第一季度至2024年第三季度的数据进行歧化分析。采用报告优势比（ROR）、比例报告比（PRR）、信息成分（IC）和经验贝叶斯几何平均（EBGM）对ae进行识别和表征。采用年龄和性别特异性亚组分析来评估AE模式。此外，采用威布尔分布分析评估AE发作的时间关系。结果脊柱融合骨折（ROR = 13.13, 95% CI: 1.73-99.86）和尾骨骨折（ROR = 3.05, 95% CI: 1.92-4.86）表现出最强的信号。dmf相关骨折风险存在性别和年龄异质性。女性患者脊柱融合骨折（ROR = 13.13）和尾骨骨折（ROR = 2.80）的信号最高，而男性患者以髌骨骨折（ROR = 4.94）和肩胛骨骨折（ROR = 3.68）为主。年龄分层显示，老年患者前臂骨折（ROR = 10.29, 95% CI: 4.24-24.96）和踝关节骨折（ROR = 5.63, 95% CI: 4.32-7.35）的风险较高，而年轻人则表现出不同的多部位骨折。发病时间（TTO）分析显示，63.62%的骨折发生在治疗周期的前2年内，中位发病时间为506天。Weibull分布模型表明，DMF的失效模式与早期失效型曲线一致。结论：DMF的使用与骨折相关ae的风险增加有关，且易感性存在人口统计学差异。这项研究为DMF在多发性硬化症治疗中的安全性提供了重要的见解，强调了对高危人群保持警惕的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.