Christensen Ronja, Cruciani Alessandro, Al-Araji Sarmad, Bianchi Alessia, Chard Declan, Fourali Samih, Hamed Weaam, Hammam Ahmed, He Anna, Kanber Baris, Maccarrone Davide, Moccia Marcello, Mohamud Suraya, Nistri Riccardo, Passalis Anestis, Pozzilli Valeria, Prados Carrasco Ferran, Samdanidou Eirini, Song Joy, Wingrove Jed, Yam Charmaine, Yiannakas Marios, Thompson Alan J, Toosy Ahmed, Hacohen Yael, Barkhof Frederik, Ciccarelli Olga
UCL Queen Square Institute of Neurology, UCL, London, UK
Queen Square MS Centre, Department of Neuroinflammation, UCL, London, UK.
BMJ Open. 2025 Sep 25;15(9):e103440. doi: 10.1136/bmjopen-2025-103440.
Multiple sclerosis (MS) is a chronic neurological condition that affects approximately 150 000 people in the UK and presents a significant healthcare burden, including the high costs of disease-modifying treatments (DMTs). DMTs have substantially reduced the risk of relapse and moderately reduced disability progression. Patients exhibit a wide range of responses to available DMTs. The Predicting Optimal INdividualised Treatment response in MS (POINT-MS) cohort was established to predict the individual treatment response by integrating comprehensive clinical phenotyping with imaging, serum and genetic biomarkers of disease activity and progression. Here, we present the baseline characteristics of the cohort and provide an overview of the study design, laying the groundwork for future analyses.
POINT-MS is a prospective, observational research cohort and biobank of 781 adult participants with a diagnosis of MS who consented to study enrolment on initiation of a DMT at the Queen Square MS Centre (National Hospital of Neurology and Neurosurgery, University College London Hospital NHS Trust, London) between 01/07/2019 and 31/07/2024. All patients were invited for clinical assessments, including the expanded disability status scale (EDSS) score, brief international cognitive assessment for MS and various patient-reported outcome measures (PROMs). They additionally underwent MRI at 3T, optical coherence tomography and blood tests (for genotyping and serum biomarkers quantification), at baseline (i.e., within 3 months from commencing a DMT), and between 6-12 (re-baseline), 18-24, 30-36, 42-48 and 54-60 months after DMT initiation.
748 participants provided baseline data. They were mostly female (68%) and White (75%) participants, with relapsing-remitting MS (94.3%), and with an average age of 40.8 (±10.9) years and a mean disease duration of 7.9 (±7.4) years since symptom onset. Despite low disability (median EDSS 2.0), cognitive impairment was observed in 40% of participants. Most patients (98.4%) had at least one comorbidity. At study entry, 59.2% were treatment naïve, and 83.2% initiated a high-efficacy DMT. Most patients (76.4%) were in either full- or part-time employment. PROMs indicated heterogeneous impairments in physical and mental health, with a greater psychological than physical impact and with low levels of fatigue. When baseline MRI scans were compared with previous scans (available in 668 (89%) patients; mean time since last scan 9±8 months), 26% and 8.5% of patients had at least one new brain or spinal cord lesion at study entry, respectively. Patients showed a median volume of brain lesions of 6.14 cm, with significant variability among patients (CI 1.1 to 34.1). When brain tissue volumes z-scores were obtained using healthy subjects (N=113, (mean age 42.3 (± 11.8) years, 61.9% female)) from a local MRI database, patients showed a slight reduction in the volumes of the whole grey matter (-0.16 (-0.22 to -0.09)), driven by the deep grey matter (-0.47 (-0.55 to -0.40)), and of the whole white matter (-0.18 (-0.28 to -0.09)), but normal cortical grey matter volumes (0.10 (0.05 to 0.15)). The mean upper cervical spinal cord cross-sectional area (CSA), as measured from volumetric brain scans, was 62.3 (SD 7.5) mm. When CSA z-scores were obtained from the same healthy subjects used for brain measures, patients showed a slight reduction in CSA (-0.15 (-0.24 to -0.10)).
Modelling with both standard statistics and machine learning approaches is currently planned to predict individualised treatment response by integrating all the demographic, socioeconomic, clinical data with imaging, genetic and serum biomarkers. The long-term output of this research is a stratification tool that will guide the selection of DMTs in clinical practice on the basis of the individual prognostic profile. We will complete long-term follow-up data in 4 years (January 2029). The biobank and MRI repository will be used for collaborative research on the mechanisms of disability in MS.
多发性硬化症（MS）是一种慢性神经疾病，在英国约有15万人受其影响，带来了巨大的医疗负担，包括疾病修正治疗（DMTs）的高昂费用。DMTs已大幅降低了复发风险，并适度减缓了残疾进展。患者对现有DMTs的反应范围广泛。建立了预测MS个体最佳治疗反应（POINT-MS）队列，通过整合全面的临床表型与疾病活动和进展的影像学、血清及遗传生物标志物来预测个体治疗反应。在此，我们展示该队列的基线特征，并概述研究设计，为未来分析奠定基础。
POINT-MS是一个前瞻性观察性研究队列及生物样本库，包含781名诊断为MS的成年参与者，他们于2019年7月1日至2024年7月31日期间在女王广场MS中心（伦敦大学学院医院国民保健服务信托基金神经学和神经外科国家医院）开始使用DMT时同意参与研究。所有患者均接受临床评估，包括扩展残疾状态量表（EDSS）评分、MS简短国际认知评估以及各种患者报告结局指标（PROMs）。他们还在基线时（即开始使用DMT后的3个月内）以及DMT开始后的6 - 12个月（重新基线）、18 - 24个月、30 - 36个月、42 - 48个月和54 - 60个月接受了3T MRI、光学相干断层扫描和血液检查（用于基因分型和血清生物标志物定量）。
748名参与者提供了基线数据。他们大多为女性（68%）和白人（75%），患有复发缓解型MS（94.3%），平均年龄为40.8（±10.9）岁，自症状出现以来的平均病程为7.9（±7.4）年。尽管残疾程度较低（EDSS中位数为2.0），但40%的参与者存在认知障碍。大多数患者（98.4%）至少有一种合并症。在研究开始时，59.2%的患者未接受过治疗，83.2%的患者开始使用高效DMT。大多数患者（76.4%）处于全职或兼职工作状态。PROMs表明在身心健康方面存在异质性损伤，心理影响大于身体影响，且疲劳程度较低。当将基线MRI扫描与先前扫描（668名（89%）患者可获取；距上次扫描的平均时间为9±8个月）进行比较时，分别有26%和8.5%的患者在研究开始时至少有一个新的脑或脊髓病变。患者脑病变的中位数体积为6.14 cm，患者之间存在显著差异（CI为1.1至34.1）。当使用来自当地MRI数据库的健康受试者（N = 113，（平均年龄42.3（±11.8）岁，61.9%为女性））获得脑组织体积z分数时，患者的全灰质体积（-0.16（-0.22至-0.09））略有减少，由深部灰质（-0.47（-0.55至-0.40））和全白质（-0.18（-0.28至-0.09））驱动，但皮质灰质体积正常（0.10（0.05至0.15））。从容积脑扫描测量的上颈脊髓平均横截面积（CSA）为62.3（SD 7.5）mm。当从用于脑测量的相同健康受试者获得CSA z分数时，患者的CSA略有减少（-0.15（-0.24至-0.10））。
目前计划采用标准统计学和机器学习方法进行建模，通过整合所有人口统计学、社会经济、临床数据与影像学、遗传和血清生物标志物来预测个体化治疗反应。这项研究的长期成果是一种分层工具，将根据个体预后特征指导临床实践中DMTs的选择。我们将在4年内（2029年1月）完成长期随访数据。生物样本库和MRI储存库将用于MS残疾机制的合作研究。
