MS is a chronic incurable and devastating inflammatory - neurodegenerative disorder of the central nervous system. There are an estimated 2.4M people with multiple sclerosis (pwMS). Scotland has one of the highest prevalence for MS in the world with 240 per 100'000 of the population having MS at any given time and with an incidence rate of 8.76 per 100'000. It is the leading non-traumatic cause of neurological disability in young adults across the industrialised world, and 85% of prevalent cases are in people of working age.

Despite important advances in diagnostics and treatment for the newly diagnosed pwMS, there remain major unsolved challenges. These include the inability to predict disease course and prognosis for newly diagnosed patients. MS in this regard is distinct to other degenerative brain diseases that have a uniform and predictable "downward" natural history. In contrast, MS is inherently unpredictable and variable. For example, some pwMS will, without treatment, experience a mild course with negligible disability after many years whilst others are seriously disabled within a few years. Therefore, at the point of diagnosis of MS, today the investigators are unable to predict whether the individual is destined to have mild, intermediate or a severe disease course noting that the disease is chronic and plays out over 30+ years. Furthermore, the range of disabilities that pwMS endure are varied and many and extend beyond physical disability. Yet, "invisible" but devastating disability including fatigue, pain and cognition, remain poorly studied and understood. As a consequence of these knowledge gaps, pwMS are unable to make informed lifestyle or treatment decision choices. FutureMS aims to address these important knowledge gaps.

Against this background, FutureMS supported by SMS Scotland was established (2015 - 2021). FutureMS is a national inception cohort study of 440 newly diagnosed people with MS that combines clinical, imaging, genomic, health and lifestyle data using a Scottish informatics platform. FutureMS is very much a key plank of the wider ambition for Scotland to lead in the area of precision medicine with a special focus on disorders, such as MS, with high morbidity and cost to the individual and society. Scotland is ideally placed to lead in precision medicine for MS. This reflects disproportionate per capita disease burden plus various national assets including e-health infrastructural strengths, unitary single health provider, single health identifier and 5 research intensive medical universities with many world-leading researchers in both the laboratory and clinical science of MS. Many of these researchers are also investigators in the MS Society Centre of Excellence - one of only two UK flagship centres supported by the MS Society - based in Edinburgh (Director - Siddharthan Chandran).

Next phase for FutureMS - Wave 2. The ultimate objective of FutureMS-2 is to contribute to the generation of validated and quantitative precision medicine tools that will allow individualised disease course prediction and personalised treatment. To fully exploit this national resource and realise its unprecedented value, there is a need to follow up the FutureMS cohort over time and "re-measure" key metrics of disease activity and its impact on the health and wealth of the individual. The wider goals of Wave 2 are to further drive the agenda and ambition of 4Ps (prevent, personalise, predict and participate) medicine for MS. It is the investigators' intention to grow, in particular, the "participatory" elements of this programme working with and advised/guided by the FutureMS "lived experience panel". This study has been shaped by these discussions and details the scientific justification and methodology to allow two follow up epochs of the original cohort at c.5 years (Wave 2) and c.10 years after diagnosis (Wave 3). Eight-ten years is the approximate average time by which the majority of individuals, without treatment, with RRMS will transition to the progressive phase of MS.