Journal Article

Single-centre, prospective cohort to predict optimal individualised treatment response in multiple sclerosis (POINT-MS): a cohort profile

Stutters, Jonathan, Leary, Siobhan, Collorone, Sara, Pansari, Fatima, Yam, Charmaine, Toorop, Alyssa, Wright, Sarah, Goodkin, Olivia, Parker, Chloe, Yiannakas, Marios, Panella, Elena, Cruciani, Alessandro, Barkhof, Frederik, Wilson, Heather, Stuart, Michaela, Hammam, Ahmed, Kurd, Mohammad, Mohamud, Suraya, Gandini Wheeler-Kingshott, Claudia Angela, Al-Araji, Sarmad, He, Anna, Bianchi, Alessia, Maccarrone, Davide, Haagenrud, Hanne, Moccia, Marcello, Pozzilli, Valeria, Wingrove, Jed, Christensen, Ronja, Toosy, Ahmed, Ciccarelli, Olga, Angelis, Floriana De, Thompson, Alan J, Samdanidou, Eirini, Hamed, Weaam, Passalis, Anestis, Brownlee, Wallace, Song, Joy, Chard, Declan, Khaleeli, Zhaleh, Trip, Anand, Chataway, Jeremy, Zhang, Le, Fourali, Samih, Kanber, Baris, Champas, Dimitrios, Swanton, Josephine, Hacohen, Yael, Solanky, Bhavana, Aojula, Anuriti, Prados Carrasco, Ferran, Eshaghi, Arman, Nistri, Riccardo, Chung, Karen

2025

Overview

PurposeMultiple 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.ParticipantsPOINT-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.Findings to date748 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 cm3, 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) mm2. 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)).Future plansModelling 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.

• Publisher: British Medical Journal Publishing Group,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult / Biomarkers / Biomarkers - blood / Clinical Decision-Making / Clinical outcomes / Cognition / Cohort Profile / Demography / Disability Evaluation / Disease control / Disease Progression / Drug Utilization / Ethics / Female / Hospitals / Humans / Longitudinal studies / Magnetic Resonance Imaging / Male / Memory / Middle Aged / Multiple sclerosis / Multiple Sclerosis - drug therapy / Neurology / Neuropsychology / Patient Reported Outcome Measures / Patients / Precision Medicine / Prospective Studies / Spinal cord / Tomography / Treatment Outcome / Verbal learning