Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 100 High St., Buffalo, NY 14203, United States.
Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 100 High St., Buffalo, NY 14203, United States; IRCCS, Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy.
Mult Scler Relat Disord. 2022 Nov;67:104187. doi: 10.1016/j.msard.2022.104187. Epub 2022 Sep 18.
New/enlarging T2 lesion count and T2-lesion volume (LV) are used as conventional secondary endpoints in clinical trials of patients with multiple sclerosis (PwMS). However, those outcomes may have several limitations, such as inability to account for heterogeneity of lesion formation/enlargement frequency and their dynamic volumetric behavior. Measurement of volume rather than count of new/enlarging lesions may be more representative outcome of dynamic changes over time.
To investigate whether new/enlarging T2-LV is more predictive of confirmed disability progression (CDP), compared to total T2-LV or new/enlarging T2 lesion count over long-term follow-up.
We studied 176 early relapsing-remitting PwMS who were followed with annual MRI examinations over 10 years. T2-LV, new/enlarging T2-LV, and new/enlarging lesion count were determined. Cumulative count/volumes were obtained. 10-year CDP was confirmed after 48-weeks. ANCOVA analysis detected MRI outcome differences in stable (n = 76) and CDP (n = 100) groups at different time points, after correction for multiple comparisons.
PwMS with CDP had greater cumulative new/enlarging T2-LV at 4 years (p = 0.049), and enlarging T2-LV at 4- (p = 0.039) and 6-year follow-up (p = 0.032), compared to stable patients. PwMS with CDP did not differ from stable ones in new/enlarging T2 lesion count or total T2-LV at any of the study timepoints. PwMS with Expanded Disability Status Scale change >2.0 had significantly greater enlarging T2 lesion count (p = 0.01) and enlarging T2-LV (p = 0.038) over the 10-year follow-up.
Enlargement of T2 lesions is more strongly associated with long-term disability progression compared to other conventional T2 lesion-based outcomes.
新/增大 T2 病灶计数和 T2 病灶体积（LV）被用作多发性硬化症（PwMS）患者临床试验中的常规次要终点。然而，这些结果可能存在一些局限性，例如无法解释病变形成/扩大频率的异质性及其动态体积行为。测量体积而不是新/增大病变的数量可能更能代表随时间的动态变化的结果。
研究新/增大 T2-LV 是否比总 T2-LV 或新/增大 T2 病变计数更能预测长期随访中的确诊残疾进展（CDP）。
我们研究了 176 例早期复发缓解型 PwMS，他们在 10 年内每年接受 MRI 检查。确定 T2-LV、新/增大 T2-LV 和新/增大 T2 病变计数。获得累积计数/体积。在 48 周后确认 10 年 CDP。ANCOVA 分析在不同时间点检测稳定（n=76）和 CDP（n=100）组的 MRI 结果差异，校正多次比较后。
与稳定患者相比，CDP 患者在 4 年（p=0.049）、4-（p=0.039）和 6 年随访时（p=0.032）累积新/增大 T2-LV 更大。在任何研究时间点，CDP 患者的新/增大 T2 病变计数或总 T2-LV 均与稳定患者无差异。扩展残疾状态量表变化>2.0 的 PwMS 在 10 年随访期间具有显著更大的增大 T2 病变计数（p=0.01）和增大 T2-LV（p=0.038）。
与其他基于 T2 病变的常规结局相比，T2 病变的扩大与长期残疾进展的相关性更强。
