Antibiotic drug use in the five years preceding the diagnosis of multiple sclerosis

IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Multiple sclerosis and related disorders Pub Date : 2025-02-28 DOI:10.1016/j.msard.2025.106366
Sonia Darvishi , Ewan Donnachie , Paula Anne Uibel , Martina Flaskamp , Christiane Gasperi , Alexander Hapfelmeier , Bernhard Hemmer
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Abstract

Background

Microbiota may play a role in autoimmune disease pathogenesis, including multiple sclerosis (MS). Antibiotic use disrupts the microbiome and may increase the risk of autoimmune diseases. We evaluated the relationship between MS diagnosis and antibiotic, antimycotic and antiviral drug use in the 5 years preceding diagnosis.

Method

Our population-based case-control study used German ambulatory claims data from 2012 to 2022. We defined cohorts of 13,053 MS patients, 22,898 Crohn's disease patients, and 15,037 matched controls without autoimmune diseases, aged 21–70. Logistic and Poisson regression models explored the relationship between MS diagnosis and antimicrobial usage. Two sub-analyses were performed: a separate analysis of patients with clinically isolated syndrome (CIS) and a sensitivity analysis of newly diagnosed MS patients without preceding neurological symptoms.

Results

Patients with MS had higher exposure to antibiotic (Odd Ratio (OR) = 1.27, 95 % CI 1.21–1.33), antimycotic (OR = 1.27, 95 % CI 1.12–1.45), and antiviral drugs (OR = 1.28, 95 % CI 1.15–1.43) in the five years before diagnosis compared to patients with no autoimmune diseases. Similar findings were obtained for the CIS cohort and in the sensitivity analysis. Antibiotic use peaked 5 years before MS diagnosis, declining closer to diagnosis, while antiviral and antimycotic drug use showed the opposite. This effect was not observed in the sensitivity analysis and CIS cohorts. Antibiotic use was higher in Crohn's disease than in MS (OR = 0.86, 95 % CI 0.82–0.90), with no consistent differences in antimycotic and antiviral use.

Conclusions

The association and kinetic of antibiotic use before MS and CIS diagnosis supports the role of microbiota in MS pathogenesis and suggests antibiotic use to be related to the development of autoimmune diseases, including MS. Additional studies are warranted to clarify whether increased antibiotic use is part of the MS prodrome or a true risk factor for MS.
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多发性硬化症诊断前5年抗生素使用情况
微生物群可能在自身免疫性疾病的发病机制中发挥作用,包括多发性硬化症(MS)。抗生素的使用会破坏微生物群,并可能增加自身免疫性疾病的风险。我们评估了MS诊断与诊断前5年内抗生素、抗真菌药物和抗病毒药物的使用之间的关系。方法我们基于人群的病例对照研究使用了2012年至2022年德国门诊索赔数据。我们定义了年龄21-70岁的13,053名MS患者,22,898名克罗恩病患者和15,037名无自身免疫性疾病的匹配对照。Logistic和泊松回归模型探讨了MS诊断与抗菌药物使用之间的关系。进行了两个亚分析:临床孤立综合征(CIS)患者的单独分析和新诊断的没有先前神经系统症状的MS患者的敏感性分析。结果与无自身免疫性疾病的患者相比,MS患者在诊断前5年内对抗生素(奇数比(OR) = 1.27, 95% CI 1.21-1.33)、抗真菌药物(OR = 1.27, 95% CI 1.12-1.45)和抗病毒药物(OR = 1.28, 95% CI 1.15-1.43)的暴露量较高。在CIS队列和敏感性分析中也得到了类似的结果。抗生素的使用在MS诊断前5年达到高峰,在接近诊断时下降,而抗病毒和抗真菌药物的使用则相反。在敏感性分析和CIS队列中未观察到这种效应。克罗恩病的抗生素使用高于多发性硬化症(OR = 0.86, 95% CI 0.82-0.90),抗真菌药和抗病毒药物的使用没有一致的差异。结论:MS和CIS诊断前抗生素使用的相关性和动力学支持微生物群在MS发病机制中的作用,并提示抗生素使用与自身免疫性疾病(包括MS)的发展有关,需要进一步的研究来阐明抗生素使用增加是MS前驱症状的一部分还是MS的真正危险因素。
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来源期刊
CiteScore
5.80
自引率
20.00%
发文量
814
审稿时长
66 days
期刊介绍: Multiple Sclerosis is an area of ever expanding research and escalating publications. Multiple Sclerosis and Related Disorders is a wide ranging international journal supported by key researchers from all neuroscience domains that focus on MS and associated disease of the central nervous system. The primary aim of this new journal is the rapid publication of high quality original research in the field. Important secondary aims will be timely updates and editorials on important scientific and clinical care advances, controversies in the field, and invited opinion articles from current thought leaders on topical issues. One section of the journal will focus on teaching, written to enhance the practice of community and academic neurologists involved in the care of MS patients. Summaries of key articles written for a lay audience will be provided as an on-line resource. A team of four chief editors is supported by leading section editors who will commission and appraise original and review articles concerning: clinical neurology, neuroimaging, neuropathology, neuroepidemiology, therapeutics, genetics / transcriptomics, experimental models, neuroimmunology, biomarkers, neuropsychology, neurorehabilitation, measurement scales, teaching, neuroethics and lay communication.
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