Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Center for Biomedical Imaging at the Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, USA.
BMC Neurol. 2024 Oct 8;24(1):378. doi: 10.1186/s12883-024-03888-6.
Brain volume loss (BVL) has been identified as a predictor of disability progression in relapsing multiple sclerosis (RMS). As many available disease-modifying treatments (DMTs) have shown an effect on slowing BVL, this is becoming an emerging clinical endpoint in RMS clinical trials.
In this study, a systematic literature review was conducted to identify BVL results from randomized controlled trials of DMTs in RMS. Indirect treatment comparisons (ITCs) were conducted to estimate the relative efficacy of DMTs on BVL using two approaches: a model-based meta-analysis (MBMA) with adjustment for measurement timepoint and DMT dosage, and a network meta-analysis (NMA).
In the MBMA, DMTs associated with significantly reduced BVL versus placebo at two years included fingolimod (mean difference [MD] = 0.25; 95% confidence interval [CI] = 0.15 - 0.36), ozanimod (MD = 0.26; 95% CI = 0.12 - 0.41), teriflunomide (MD = 0.38; 95% CI = 0.20 - 0.55), alemtuzumab (MD = 0.38; 95% CI = 0.10 - 0.67) and ponesimod (MD = 0.71; 95% CI = 0.48 - 0.95), whereas interferons and natalizumab performed the most poorly. The results of NMA analysis were generally comparable with those of the MBMA.
Limitations of these analyses included the potential for confounding due to pseudoatrophy, and a lack of long-term clinical data for BVL. Our findings suggest that important differences in BVL may exist between DMTs. Continued investigation of BVL in studies of RMS is important to complement traditional disability endpoints, and to foster a better understanding of the mechanisms by which DMTs can slow BVL.
脑容量损失（BVL）已被确定为复发型多发性硬化症（RMS）残疾进展的预测指标。由于许多现有的疾病修正治疗（DMT）已显示出对减缓 BVL 的作用，因此这在 RMS 临床试验中成为一个新兴的临床终点。
本研究进行了系统文献回顾，以确定 RMS 中 DMT 随机对照试验的 BVL 结果。采用两种方法进行间接治疗比较（ITC），以估计 DMT 对 BVL 的相对疗效：一种是基于模型的荟萃分析（MBMA），对测量时间点和 DMT 剂量进行调整，另一种是网络荟萃分析（NMA）。
在 MBMA 中，与安慰剂相比，两年时 DMT 与 BVL 显著降低相关，包括 fingolimod（MD=0.25；95%置信区间 [CI]=0.15-0.36）、ozanimod（MD=0.26；95%CI=0.12-0.41）、teriflunomide（MD=0.38；95%CI=0.20-0.55）、alemtuzumab（MD=0.38；95%CI=0.10-0.67）和 ponesimod（MD=0.71；95%CI=0.48-0.95），而干扰素和那他珠单抗的效果最差。NMA 分析的结果与 MBMA 的结果基本一致。
这些分析存在的局限性包括假性萎缩引起的混杂因素，以及缺乏 BVL 的长期临床数据。我们的研究结果表明，DMT 之间可能存在 BVL 的重要差异。在 RMS 研究中继续研究 BVL 对于补充传统的残疾终点以及深入了解 DMT 减缓 BVL 的机制非常重要。
