Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, USA.
Mult Scler Relat Disord. 2021 Sep;54:103086. doi: 10.1016/j.msard.2021.103086. Epub 2021 Jun 24.
Few satisfyingly effective treatments exist for patients with Secondary Progressive Multiple Sclerosis (SPMS). Our goal in conducting this review is to highlight clinical outcomes and study design, which may be applied to future phase III clinical trials for patients with SPMS.
A review of the available literature of phase III clinical trials since 1990 that specifically studied patients with SPMS. PubMed and ClinicalTrials.org were searched using appropriate terms.
Expanded Disability Status Scale (EDSS) was most often used as an outcome measure, with time to confirmed disability progression at three months being used most often. Components of the Multiple Sclerosis Functional Composite (MSFC) were the next most frequent primary outcome measure used. Patient Reported Outcomes (PROs) were frequently used as secondary outcome measures with specific PROs more successful than others. MRI measures related to brain parenchymal volume have recently started to be used in phase III clinical trials.
Some successful trials may have been related to patient selection for less inflammatory disease, which confounds the comparison between successful trials. Time to confirmed disability at three months or changes in composite MSFC are reasonable primary outcome measures to use in future SPMS trials with a suggestion that the MSFC may be more sensitive to progressive disease changes. PROs and MRI measures following brain parenchymal volume are reasonable secondary outcome measures to incorporate into future phase III trials in SPMS.
对于继发进展型多发性硬化症（SPMS）患者，目前几乎没有令人满意的有效治疗方法。我们进行这项综述的目的是强调可能应用于 SPMS 患者未来 III 期临床试验的临床结果和研究设计。
对 1990 年以来发表的 III 期临床试验的相关文献进行综述，这些试验专门研究 SPMS 患者。使用适当的术语在 PubMed 和 ClinicalTrials.org 上进行搜索。
扩展残疾状况量表（EDSS）最常用于作为结局测量指标，最常用于评估三个月时确认的残疾进展时间。多发性硬化功能综合（MSFC）的组成部分是下一个最常用的主要结局测量指标。患者报告的结果（PROs）经常被用作次要结局测量指标，特定的 PROs 比其他的更成功。与脑实质体积相关的 MRI 测量指标最近开始在 III 期临床试验中使用。
一些成功的试验可能与选择炎症性疾病较少的患者有关，这使得成功试验之间的比较变得复杂。未来 SPMS 试验中，三个月时的确认残疾时间或 MSFC 变化是合理的主要结局测量指标，表明 MSFC 可能对进展性疾病变化更敏感。在 SPMS 的未来 III 期试验中，PROs 和基于脑实质体积的 MRI 测量指标是合理的次要结局测量指标。
