BACKGROUND In multiple sclerosis (MS), up to 57% of white matter lesions are chronically active. These slowly expanding lesions (SELs) contribute to disability progression. OBJECTIVE The aim of this study is to compare fingolimod and natalizumab effects on progressive linearly enlarging lesions (i.e. SELs), a putative biomarker of smouldering inflammation. METHODS Relapsing-remitting MS patients starting fingolimod (n = 24) or natalizumab (n = 28) underwent 3T brain magnetic resonance imaging (MRI) at baseline, months 6, 12 and 24. SELs were identified among baseline-visible lesions showing ⩾ 12.5% of annual increase, calculated by linearly fitting the Jacobian of the nonlinear deformation field between timepoints obtained combining T1- and T2-weighted scans. SEL burden, magnetization transfer ratio (MTR) and T1 signal intensity were compared using linear models. RESULTS The prevalences of fingolimod (75%) and natalizumab patients (46%) with ⩾ 1 SEL were not significantly different (adjusted-p = 0.08). Fingolimod group had higher SEL number and volume (adjusted-p ⩽ 0.047, not false discovery rate (FDR) survived). In both groups, SELs versus non-SELs showed lower MTR and T1 signal intensity (adjusted-p ⩽ 0.01, FDR-survived). Longitudinally, non-SEL MTR increased in both treatment groups (adjusted-p ⩽ 0.005, FDR-survived). T1 signal intensity decreased in SELs with both treatments (adjusted-p ⩽ 0.049, FDR-survived in fingolimod group) and increased in natalizumab non-SELs (adjusted-p = 0.03, FDR-survived). CONCLUSION The effects of natalizumab and fingolimod on SEL occurrence seem modest, with natalizumab being slightly more effective. Both treatments may promote reparative mechanisms in stable or chronic inactive lesions.

中文翻译：

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芬戈莫德或那他珠单抗治疗多发性硬化症缓慢扩大病变的发生和微观结构特征

背景在多发性硬化症 (MS) 中，多达 57% 的白质病变是慢性活动的。这些缓慢扩大的病变 (SEL) 会导致残疾进展。目的 本研究的目的是比较芬戈莫德和那他珠单抗对渐进性线性扩大病变 (即 SEL) 的影响，这是一种假定的闷烧性炎症生物标志物。方法 开始接受芬戈莫德 (n = 24) 或那他珠单抗 (n = 28) 的复发缓解型 MS 患者在基线、第 6、12 和 24 个月时接受了 3T 脑磁共振成像 (MRI)。在基线可见病变中鉴定出 SELs，显示 ⩾ 12.5每年增加的百分比，通过线性拟合结合 T1 和 T2 加权扫描获得的时间点之间非线性变形场的雅可比行列式计算。SEL 负担，使用线性模型比较磁化转移比 (MTR) 和 T1 信号强度。结果 具有⩾ 1 SEL 的芬戈莫德 (75%) 和那他珠单抗患者 (46%) 的患病率没有显着差异（调整后的 p = 0.08）。芬戈莫德组具有更高的 SEL 数量和体积（调整后的 p ⩽ 0.047，未存活的假发现率 (FDR)）。在两组中，SEL 与非 SEL 显示出较低的 MTR 和 T1 信号强度（调整后的 p ⩽ 0.01，FDR 存活）。纵向上，两个治疗组的非 SEL MTR 均增加（调整后的 p ⩽ 0.005，FDR 存活）。两种治疗的 SEL 中 T1 信号强度均降低（调整后的 p ⩽ 0.049，芬戈莫德组中 FDR 存活），那他珠单抗非 SEL 中的 T1 信号强度增加（调整后 p = 0.03，FDR 存活）。结论那他珠单抗和芬戈莫德对 SEL 发生的影响似乎不大，那他珠单抗稍微更有效。这两种治疗都可以促进稳定或慢性非活动性病变的修复机制。