Multiple sclerosis (MS) is an inflammatory disease of the brain and the spinal cord. It shows the highest inflammatory activity during its earliest stages, especially in children. Poorly controlled disease in children with active MS leads to permanent disability as early as their third decade of life.
Dr Sifat Sharmin and her team hypothesise that the risks of frequent attacks of MS and faster development of disability in this vulnerable population can be reduced with the appropriate choice of highly effective disease modifying therapies (DMTs). However, the lack of robust evidence in the use highly effective therapies in children with MS poses a challenge, impeding informed treatment decisions tailored to their unique needs.
To address this, Dr Sharmin’s study will use advanced statistical methods to analyse comprehensive data from three registries, both national and international. We will simulate the natural course of MS in children, progressing from negligible disability to secondary progressive MS, while evaluating the impact of DMTs on this trajectory.
Subsequently, the team will evaluate the justification for highly effective/high risk therapies in children and determine whether those at the highest risk of accelerated disability will receive greater benefits from such interventions. Furthermore, they will compare the effectiveness of different highly effective MS therapies in children.
This study will generate novel and conclusive evidence that will enable individualised treatment decision-making by identifying the optimal high-efficacy therapy at an early stage for children at the highest risk of experiencing worsening disability.
Over the past year, Dr Sharmin and her team established the largest cohort of individuals with paediatric-onset MS to date by combining data from three international registries (Italy, France and the global MSBase registry). Â
By analysing the combined database, Dr Sharmin showed that early treatment with highly effective therapies can reduce the risk of disability progression by up to 59% in people with paediatric-onset MS. They also found therapies that are not as effective had benefits compared to no treatment, which is particularly important for resource-limited settings where only less effective therapies are accessible.Â
This research has provided compelling evidence for using highly effective therapies early in children with MS to preserve neurological function and slow the progress of long-term disability. The findings have the potential to significantly improve the health outcomes of children with MS and have been published in the prestigious journal The Lancet Child & Adolescent Health.Â
During this project, Dr Sharmin established a collaboration with the Italian Multiple Sclerosis Register. Moving forward, Dr Sharmin and her team will focus on personalising the use of highly effective therapies in children with MS. They will assess whether highly effective therapies reduce relapses and worsening of disability in children with active relapsing remitting MS. Dr Sharmin and her team will also begin comparing the effectiveness of natalizumab, fingolimod and B-cell therapies in children.Â
Sharmin S, Roos I, Malpas CB, et al. Disease-modifying therapies in managing disability worsening in paediatric-onset multiple sclerosis: a longitudinal analysis of global and national registries. The Lancet Child & Adolescent Health. 2024;8(5):348-57.Â
Last updated 31 March 2025
Professor Tomas Kalincik
$225,000
2024
3 years
Current project
