Very different disease course rates in secondary progressive MS

The Big MS Data Network was used for analysis showing that people with
primary progressive MS progressed at different rates during their disease.
Image: Big MS Data Network

by Dr Loretta Piccenna, Research Manager, Department of Neuroscience, Monash University

Background

People who have primary and secondary progressive forms of multiple sclerosis require great consideration both in clinical practice and research due to huge unmet needs. 

Primary and secondary progressive MS are forms in which disability from the disease continues to get worse (with time without experiencing relapses) and does not resolve. So, these forms do not respond in the same way to treatment used for the more common form, relapsing-remitting MS.

It is a challenge to manage the disability progression in the disease as available treatments are not very effective. Clinical trials of new treatments are critically needed to help people have better outcomes in the long term or to prevent the disease.

People with secondary progressive MS may present late to clinicians in their disease course. Some people do not show obvious signs of the disease, so clinicians need to diagnose the disease by going back in time. But, this is not ideal for early management and getting the best outcomes for people. 

Research at present is focused on the point when people move from relapsing-remitting MS to secondary progressive MS so they can identify this form as early as possible for management. Over five years ago, a definition was developed for secondary progressive MS for greater consistency and objectivity (1).

Previously, it was thought that all people with secondary progressive MS progressed in their disease course at the same rate. But, this evidence arose from single-site studies or studies that involved small numbers of people. 

A recently published study in people with primary progressive MS showed that people progressed at different rates during their disease, suggesting that this feature of variable progression rates might be the same in secondary progressive MS.

What did the researchers do?

Professor Helmut Butzkueven said, "We sourced data from an initiative called the Big MS Data Network and looked at Expanded Disability Status Scale (EDSS) scores for two different groups of people. One group was where people met the Lorscheider criteria for the definition of secondary progressive MS and one group was diagnosed only by a clinician’s judgement. 

"We modelled the scores over time using a statistical method - called latent class growth analysis - and compared demographic and clinical features of people to see if there were any clear or noticeable patterns."

What did the researchers find?

For both groups (3613 people diagnosed by a clinician and 7613 that met the Lorscheider criteria), the analysis showed people with secondary progressive MS progress in their disease course at very different rates. 

Three separate and unique groups were found – mild, moderate and severe (rapid increase) disability progression. 

The people in the severe group showed a younger age and lower disease duration at the start of the study follow-up time.

What do the findings mean? 

Not all people with secondary progressive MS should be managed in the same way.

To reduce the waste of time and money in future clinical trials for new treatments the classification of different disease courses can be used as the inclusion/exclusion criterion. 

In addition, people who are at high risk of disease progression in secondary progressive MS can be prioritised for clinical trials as they have the greatest need. It will increase the power of the clinical trial as there will be more disability events expected.

To further use these findings in clinical practice, researchers and clinicians should develop clinical decision-making tools to help identify people with a high risk of disease progression.

Future research should focus on understanding the high variability in disease course rates at the biological and molecular level to see what the cause is. Biomarkers and genetic profiles could also be studied between the different groups. 

See more

• Lorscheider J, Buzzard K, Jokubaitis V et al. Defining secondary progressive multiple sclerosis. Brain 2016; 139:2395 – 405. academic.oup.com/brain/article/139/9/2395/1744806
• Big Multiple Sclerosis Data Network - bigmsdata.org/ 

Reference

Signori A, Lorscheider J, Vukusic S, ... , van der Walt A, ... , Skibina O, ... , Zhu C, ... , Butzkueven H, on behalf of the Big MS Data Network. Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis from Big MS Data network. Journal of Neurology, Neurosurgery & Psychiatry Published Online First: 28 September 2022. doi: dx.doi.org/10.1136/jnnp-2022-329987