Over time, MS leads to significant disability, decreased quality of life and considerable cost to patients and society. It has been established that many disease modifying therapies (DMTs) can reduce long-term disability, especially when commenced early after disease onset. However, many questions remain regarding their optimal use.
Dr Nathaniel Lizak and his team aim to investigate the optimal use of DMTs using large datasets of MS patients from an international registry. They will focus on understanding early markers of treatment success, how to manage failure of high-efficacy DMTs in MS patients, and how to predict and optimally treat progressive MS.
This research aims to improve disability outcomes and quality of life for patients while minimising the cost and risk of long-term therapy.
Dr Nathaniel Lizak and his team have used data from MSBase, a large international registry that tracks MS treatment and health outcomes over time, to investigate treatment choices and outcomes after a highly effective MS treatment stops working well.
The study analysed data from more than 1,000 people who had relapses while taking natalizumab, a highly effective MS treatment. The study found that switching to a B-cell–targeting treatment, such as ocrelizumab or rituximab, more than halved the risk of future relapses compared with staying on natalizumab. In contrast, switching to moderately effective treatments or stopping treatment was linked with worse outcomes. This work has been published and provides practical evidence to help neurologists and people with MS make clearer decisions when a powerful treatment is no longer working well.
The team has also completed a large study looking at whether people with MS can experience lasting improvement in disability, rather than only aiming to prevent worsening. Using MSBase data from more than 60,000 people with MS, the study found that meaningful improvement can occur, particularly earlier in the disease and after starting stronger MS treatments. People who experienced lasting improvement tended to have better long-term outcomes, including staying more mobile for longer and being less likely to move into a progressive phase of MS. This work suggests that measuring improvement in disability is an important outcome in MS clinical trials and studies of MS therapies. The work has been submitted to a major neurology journal for review.
The next stage of the project is focused on progressive forms of MS, where treatment decisions are especially challenging. Dr Lizak has already identified large groups of people with primary progressive and secondary progressive MS within MSBase, built datasets to compare different treatment options, and begun analyses looking at relapses, disability progression, mobility and treatment switching. These findings will help clarify which treatments are most useful for progressive MS and which people are most likely to benefit, with the ultimate goal of preserving independence and quality of life for people living with MS.
Lizak N, Sharmin S, Horakova D, et al. Managing reactivation of multiple sclerosis during treatment with natalizumab. Multiple Sclerosis Journal 2026 Jan;32(1):121-133.
Updated 31 March 2026
$30,000
2025
3 years
Current project
