Signori Alessio, Lorscheider Johannes, Vukusic Sandra, Trojano Maria, Iaffaldano Pietro, Hillert Jan, Hyde Robert, Pellegrini Fabio, Magyari Melinda, Koch-Henriksen Nils, Sørensen Per Soelberg, Spelman Tim, van der Walt Anneke, Horakova Dana, Havrdova Eva, Girard Marc, Eichau Sara, Grand'Maison Francois, Gerlach Oliver, Terzi Murat, Ozakbas Serkan, Skibina Olga, Van Pesch Vincent, Sa Maria Jose, Prevost Julie, Alroughani Raed, McCombe Pamela A, Gouider Riadh, Mrabet Saloua, Castillo-Trivino Tamara, Zhu Chao, de Gans Koen, Sánchez-Menoyo José Luis, Yamout Bassem, Khoury Samia, Sormani Maria Pia, Kalincik Tomas, Butzkueven Helmut
Department of Health Sciences, University of Genoa, Genoa, Italy
Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
J Neurol Neurosurg Psychiatry. 2023 Jan;94(1):23-30. doi: 10.1136/jnnp-2022-329987. Epub 2022 Sep 28.
Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time.
All patients with MS collected within Big MS registries who received an SPMS diagnosis from physicians (cohort 1) or satisfied the Lorscheider criteria (cohort 2) were considered. Longitudinal Expanded Disability Status Scale (EDSS) scores were modelled by a latent class growth analysis (LCGA), using a non-linear function of time from the first EDSS visit in the range 3-4.
A total of 3613 patients with SPMS were included in the cohort 1. LCGA detected three different subgroups of patients with a mild (n=1297; 35.9%), a moderate (n=1936; 53.6%) and a severe (n=380; 10.5%) disability trajectory. Median time to EDSS 6 was 12.1, 5.0 and 1.7 years, for the three groups, respectively; the probability to reach EDSS 6 at 8 years was 14.4%, 78.4% and 98.3%, respectively. Similar results were found among 7613 patients satisfying the Lorscheider criteria.
Contrary to previous interpretations, patients with SPMS progress at greatly different rates. Our identification of distinct trajectories can guide better patient selection in future phase 3 SPMS clinical trials. Additionally, distinct trajectories could reflect heterogeneous pathological mechanisms of progression.
几十年来，国际登记处报告了多项关于原发性进展型多发性硬化症（PPMS）或继发性进展型多发性硬化症（SPMS）患者的自然史研究。在PPMS中，长期残疾轨迹存在一致的异质性。本研究的目的是确定SPMS患者中随着时间推移具有相似残疾纵向轨迹的亚组。
考虑纳入大型MS登记处收集的所有被医生诊断为SPMS的MS患者（队列1）或符合洛施奈德标准的患者（队列2）。使用从首次EDSS访视起3至4范围内时间的非线性函数，通过潜在类别增长分析（LCGA）对纵向扩展残疾状态量表（EDSS）评分进行建模。
队列1共纳入3613例SPMS患者。LCGA检测到三个不同的患者亚组，其残疾轨迹分别为轻度（n = 1297；35.9%）、中度（n = 1936；53.6%）和重度（n = 380；10.5%）。三组患者达到EDSS 6的中位时间分别为12.1年、5.0年和1.7年；8年时达到EDSS 6的概率分别为14.4%、78.4%和98.3%。在7613例符合洛施奈德标准的患者中也发现了类似结果。
与先前的解释相反，SPMS患者的进展速度差异很大。我们对不同轨迹的识别可为未来3期SPMS临床试验中更好地选择患者提供指导。此外，不同的轨迹可能反映了进展的异质性病理机制。
