Lambert Clare McGarvey, Hussain Taimoor, Peters John, Longbrake Erin E
Department of Neurology, Yale New Haven Hospital, United States of America.
Yale University, United States of America.
Mult Scler Relat Disord. 2025 Feb;94:106236. doi: 10.1016/j.msard.2024.106236. Epub 2024 Dec 24.
Numerous immunomodulatory treatments exist for multiple sclerosis (MS), including those that deplete immune cells (e.g. anti-CD20 medications), relocate immune cells (e.g. natalizumab, S1P modulators), or modulate immune subsets (e.g. fumarates). All disease-modifying treatments (DMTs) can increase infection risk which could worsen with prolonged use.
This is a retrospective, single-center, observational cohort study. We analyzed medical records of adult people with MS who took natalizumab, S1P modulators, fumarates or anti-CD20 medications for over two years between January 2013 and April 2021 at Yale. We identified severe infections (requiring hospitalization) and mild infections (identified through outpatient antibiotic prescriptions or chart reference to "infection"). We used a zero-inflated negative binomial regression to assess the effects of DMT use, treatment duration, and patient characteristics on infection likelihood and frequency, while controlling for biologic sex, body mass index, ambulatory status, Charlson Comorbidity Index (CCI), diagnosis, disease modifying therapy and treatment duration.
104 patients received natalizumab, 61 fumarates, 17 S1P modulators and 291 anti-CD20 medications, with significant baseline differences in age, diagnosis, duration of DMT use, and CCI. Mild infection rates did not differ across DMTs, but severe infections were more common in patients on fumarates. Patients with longer DMT duration or requiring a walking aid had higher mild infection rates, while those with progressive MS or on long-term fumarates had higher severe infection rates, even after controlling for other variables.
This study demonstrates how real-life practice patterns, patient factors and DMT choice can influence infection rates, differing from randomized trial patterns. Natalizumab appears safe over extended use, while fumarates were linked to more severe infections, potentially due to the clinical selection of patients with poorer baseline health. The duration of DMT use may predict mild infection rates.
针对多发性硬化症（MS）存在多种免疫调节治疗方法，包括那些消耗免疫细胞的方法（如抗CD20药物）、重新定位免疫细胞的方法（如那他珠单抗、S1P调节剂）或调节免疫亚群的方法（如富马酸盐）。所有疾病修正治疗（DMT）都会增加感染风险，且随着使用时间延长这种风险可能会加剧。
这是一项回顾性、单中心观察性队列研究。我们分析了2013年1月至2021年4月期间在耶鲁大学服用那他珠单抗、S1P调节剂、富马酸盐或抗CD20药物超过两年的成年MS患者的病历。我们确定了严重感染（需要住院治疗）和轻度感染（通过门诊抗生素处方或病历中提及“感染”来确定）。我们使用零膨胀负二项回归来评估DMT使用、治疗持续时间和患者特征对感染可能性和频率的影响，同时控制生物性别、体重指数、活动状态、Charlson合并症指数（CCI）、诊断、疾病修正治疗和治疗持续时间。
104名患者接受了那他珠单抗治疗，61名接受了富马酸盐治疗，17名接受了S1P调节剂治疗，291名接受了抗CD20药物治疗，在年龄、诊断、DMT使用持续时间和CCI方面存在显著的基线差异。不同DMT的轻度感染率没有差异，但富马酸盐治疗的患者中严重感染更为常见。DMT持续时间较长或需要使用助行器的患者轻度感染率较高，而患有进展型MS或长期使用富马酸盐的患者严重感染率较高，即使在控制了其他变量之后也是如此。
本研究表明现实生活中的实践模式、患者因素和DMT选择如何影响感染率，这与随机试验模式不同。长期使用那他珠单抗似乎是安全的，而富马酸盐与更严重的感染有关，这可能是由于对基线健康状况较差的患者进行了临床选择。DMT的使用持续时间可能预测轻度感染率。
