De Angelis Floriana, Nistri Riccardo, Wright Sarah
Department of Neuroinflammation, Faculty of Brain Sciences, Queen Square Multiple Sclerosis Centre, University College London Queen Square Institute of Neurology, University College London, London, WC1B 5EH, UK.
National Institute for Health and Care Research, Biomedical Research Centre, University College London Hospitals, London, UK.
CNS Drugs. 2025 Jan;39(1):55-80. doi: 10.1007/s40263-024-01132-w. Epub 2024 Nov 24.
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterised by inflammation, demyelination and neurodegeneration. Although several drugs are approved for MS, their efficacy in progressive disease is modest. Addressing disease progression as a treatment goal in MS is challenging due to several factors. These include a lack of complete understanding of the pathophysiological mechanisms driving MS and the absence of sensitive markers of disease progression in the short-term of clinical trials. MS usually begins at a young age and lasts for decades, whereas clinical research often spans only 1-3 years. Additionally, there is no unifying definition of disease progression. Several drugs are currently being investigated for progressive MS. In addition to new medications, the rise of new technologies and of adaptive trial designs is enabling larger and more integrated data collection. Remote assessments and decentralised clinical trials are becoming feasible. These will allow more efficient and large studies at a lower cost and with less burden on study participants. As new drugs are developed and research evolves, we anticipate a concurrent change in patient care at various levels in the foreseeable future. We conducted a narrative review to discuss the challenges of accurately measuring disease progression in contemporary MS drug trials, some new research trends and their implications for patient care.
多发性硬化症（MS）是一种慢性中枢神经系统免疫介导疾病，其特征为炎症、脱髓鞘和神经退行性变。尽管有几种药物已获批用于治疗MS，但它们对进展性疾病的疗效有限。由于多种因素，将疾病进展作为MS的治疗目标具有挑战性。这些因素包括对驱动MS的病理生理机制缺乏全面了解，以及在临床试验短期内缺乏疾病进展的敏感标志物。MS通常在年轻时发病，病程长达数十年，而临床研究通常仅持续1至3年。此外，对于疾病进展没有统一的定义。目前正在对几种药物进行进展性MS的研究。除了新药物，新技术和适应性试验设计的兴起使得能够收集更大规模、更综合的数据。远程评估和去中心化临床试验正变得可行。这些将使我们能够以更低的成本、给研究参与者带来更少负担的方式开展更高效、规模更大的研究。随着新药的研发和研究的发展，我们预计在可预见的未来，患者护理在各个层面将同时发生变化。我们进行了一项叙述性综述，以讨论当代MS药物试验中准确测量疾病进展的挑战、一些新的研究趋势及其对患者护理的影响。
