Reeves Jack A, Bartnik Alexander, Mohebbi Maryam, Ramanathan Murali, Bergsland Niels, Jakimovski Dejan, Wilding Gregory E, Salman Fahad, Schweser Ferdinand, Weinstock-Guttman Bianca, Hojnacki David, Eckert Svetlana, Bagnato Francesca, Dwyer Michael G, Zivadinov Robert
Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
Department of Pharmaceutical Sciences, State University of New York, Buffalo, New York, USA.
Ann Clin Transl Neurol. 2025 Feb;12(2):267-279. doi: 10.1002/acn3.52253. Epub 2024 Nov 18.
Baseline paramagnetic rim lesion (PRL) load predicts disease progression in people with multiple sclerosis (pwMS). Understanding how PRLs relate to other known MS-related factors, and the practical utility of PRLs in clinical trials, is crucial for informing clinical decision-making and guiding development of novel disease-modifying treatments (DMTs).
This study included 152 pwMS enrolled in a larger prospective, longitudinal cohort study who had 3T MRI scans and clinical assessments at baseline and 5- or 10-year follow-ups. PRLs were identified on baseline 3T quantitative susceptibility maps and classified as persisting, disappearing, or newly appearing at follow-up. The relationships between PRL evolution and clinical, radiological, environmental, and genetic characteristics were assessed, and clinical trial sample sizes were estimated using PRL appearance or disappearance as outcome measures.
DMT use was associated with lower odds of new PRL appearance (for high-efficacy DMTs: odds ratio = 0.088, p = 0.024), but not disappearance. Current smoking status was associated with greater baseline PRL number (B = 0.527 additional PRLs, p = 0.013). A 24-month clinical trial in people with progressive MS for a DMT that doubles the rate of PRL rim disappearance would require an estimated 118 people with progressive MS per group at 80% statistical power.
Early MS diagnosis and subsequent DMT initiation may reduce new chronic active inflammation. However, the utility of PRL disappearance or new PRL appearance as outcome measures in clinical trials is limited by potentially large sample sizes that are needed for moderate efficacy drugs.
基线顺磁性边缘病变（PRL）负荷可预测多发性硬化症患者（pwMS）的疾病进展。了解PRL与其他已知的MS相关因素之间的关系，以及PRL在临床试验中的实际应用，对于指导临床决策和新型疾病修饰治疗（DMT）的开发至关重要。
本研究纳入了152名pwMS患者，他们参与了一项更大规模的前瞻性纵向队列研究，在基线以及5年或10年随访时进行了3T MRI扫描和临床评估。在基线3T定量磁化率图上识别PRL，并将其分类为随访时持续存在、消失或新出现的病变。评估PRL演变与临床、放射学、环境和遗传特征之间的关系，并以PRL出现或消失作为结局指标估计临床试验样本量。
使用DMT与新PRL出现的几率较低相关（对于高效能DMT：优势比=0.088，p=0.024），但与消失无关。当前吸烟状态与更高的基线PRL数量相关（B=额外0.527个PRL，p=0.013）。对于一种可使PRL边缘消失率翻倍的DMT，在进行性MS患者中开展的一项为期24个月的临床试验，在80%的统计效能下，每组估计需要118名进行性MS患者。
早期MS诊断及随后开始使用DMT可能会减少新的慢性活动性炎症。然而，在临床试验中，将PRL消失或新PRL出现作为结局指标的效用受到中等效能药物所需潜在大样本量的限制。
