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Research Updates August


min read

 

Latest developments in MS research:

  • Read about the consensus statement on smouldering-associated worsening in MS.
  • Know more about the psychiatric issues associated with MS and NMOSD.
  • Learn how MRI can assist in tracking progression and selecting the most appropriate treatment for older people with MS.

These noteworthy MS news highlights and more are included in our recently published ECTRIMS Research Updates – a 30-day snapshot of global news and publications on MS research, treatment, and care.
 
ECTRIMS Research Updates can be sent to you every month, delivered straight to your inbox, via our free subscription service. Simply select all “topics” that are of interest to you, and when one of those appears in our news and publication cycle, you’ll be sure to hear from us.

Clinical

Smouldering-associated worsening in multiple sclerosis: An international consensus statement on definition, biology, clinical implications, and future directions
 
Annals of Neurology |  25 July 2024
 
‘Do you struggle to remember conversations, even when they are important?’, ‘Do you feel more distant from your partner because you can’t keep up with him/her with the usual energy?’. These are some examples that may help uncover “smouldering-associated worsening” (SAW). SAW is a concept developed by an international panel of MS experts from Europe, the US, and Canada, to include not only physical but also cognitive symptoms resulting from smouldering pathological processes in MS.
 
While many treatments can successfully reduce focal inflammatory activity, individuals with MS may still experience gradual and slow decline over time, even in the absence of relapses. This subtle worsening of symptoms and signs may not be fully captured by the current definition of progression independent of relapse activity (PIRA), which is primarily anchored on clinical scales of motor performance, such as the expanded disability status scale (EDSS) or EDSS-Plus.
 
The panel identifies several imaging and fluid biomarkers that may help detect and monitor SAW, such as paramagnetic rim lesions (PRLs), levels of neurofilament light (NfL) concentrations in the central nervous system, and measurements of global and regional brain atrophy. The MS experts also propose several questions to assist in detecting SAW in clinical practice, addressing physical, cognitive, and social domains. Finally, they advocate for a holistic management approach to minimise the impact of SAW.

The ageing central nervous system in multiple sclerosis: the imaging perspective
 
Brain |  July 2024  
 
This paper presents the conclusions from last year’s international meeting of the Magnetic Resonance Imaging in MS (MAGNIMS) network, held in Milan. The meeting, titled “Imaging the ageing CNS in multiple sclerosis”, focused on reviewing the current understanding of MRI in studying the ageing central nervous system in MS. The experts discussed how MRI can assist in tracking disease progression and in selecting the most suitable treatment strategies. Key topics included the clinical, immune-pathological, and MRI characteristics of ageing in MS. The experts reviewed how MRI techniques can be applied to investigate specific pathological processes in MS, which can enhance our understanding of the interaction between ageing and MS mechanisms, support early and accurate diagnosis, and assist in monitoring treatment.

 
Diversity in clinical trials

 Efficacy of Ofatumumab and Teriflunomide in Patients With Relapsing MS From Racial/Ethnic Minority Groups
 
Neurology | 18 July 2024 
 
Choosing the right therapy for each person with MS is very important. A post hoc analysis was run to determine the efficacy and safety profile of ofatumumab – an anti-CD20 monoclonal antibody – vs teriflunomide – an immunomodulatory agent – in participants from different racial/ethnic groups enrolled in the ASCLEPIOS I and II trials. The 1,882 participants self-identified as non-Hispanic Black (3.4%), non-Hispanic Asian (3.8%), Hispanic/Latino (7.7%), or non-Hispanic White (81.7%). Over 12-24 months, participants across all racial/ethnic groups who were treated with ofatumumab had higher rates of no evidence of disease activity (NEDA) than those treated with teriflunomide. Both treatments were well tolerated. Both efficacy and safety of ofatumumab were similar across groups. Slightly higher rates of adverse events, serious adverse events, and serious infections were reported in non-Hispanic Black participants treated with ofatumumab than in other groups. 33.3% of non-Hispanic Asian participants receiving ofatumumab had fever.
 
 
Generalising the results of clinical trials if participants are not from diverse racial and ethnic groups
 
Neurology | 13 August 2024 
 
Personalising a treatment approach can be challenging, particularly given the variety of aspects that can influence clinical outcomes. While people with MS have different backgrounds, races and ethnicities, clinical trials often lack diversity. This seems to be a widespread problem in medical research. To address this issue, it would be crucial to involve diverse communities from the earliest stages of conception and design of clinical trials. This is important for ensuring that research findings are applicable to all people with MS in real-world.
 
It is essential to test the treatment on a population that reflects the real-world characteristics of those who will eventually receive it. By including a broader range of participants, researchers can better understand how different groups respond to treatments and identify any specific needs or risks. This editorial suggests that researchers should work together with regulatory agencies, pharmaceutical companies, and associations of patients. This collaboration could help create more diverse trial committees that better represent different populations.
 

Aging and MS

 
Multiple sclerosis in Denmark (1950–2023): mean age, sex distribution, incidence and prevalence
 
Brain |  20 July 2024 
 
“The mean age of people with MS is increasing”. Is it true? To provide evidence supporting this statement, a study analysed the mean and median age, age and sex distribution, incidence, and prevalence of the Danish population with MS every year from 1950 to 2023. 28,145 individuals with MS, from the Danish MS Registry, were included in the study. The results show that indeed the mean age of the Danish population with MS has increased, but not as much as expected. From 1980 to 2023, the mean age of people with MS in Denmark increased from 52.4 to 54.2 years. There was a drop to 51.2 years in 2005, possibly due to earlier diagnoses made possible by new treatments and improved diagnostic criteria. Earlier diagnoses may have led to more cases being diagnosed at a younger age. Interestingly, since 2007, the proportion of people with MS aged 65 years or older is rising, likely due to improved treatments and supportive care.
 

Comorbidities
 

The burden of psychiatric morbidity in Multiple Sclerosis, AQP4-antibody NMOSD and MOGAD before and after neurological diagnosis
 
Multiple Sclerosis and Related Disorders |  18 July 2024
 
Psychiatric disorders are observed in the prodromal phase of MS. A retrospective observational study was conducted on 399 individuals with MS, Aquaporin-4-Antibody Neuromyelitis Optica Spectrum Disorders (AQP4-Ab NMOSD) and Myelin Oligodendrocyte Glycoprotein-Antibody Associated Disease (MOGAD), who were seen at the National Neuroscience Institute (NNI) in Singapore.
 
The study found that 5.2% of people with MS had psychiatric disorders before their neurological diagnosis, which is higher compared to 1% in those with NMOSD and none in those with MOGAD. In line with other studies, the most common psychiatric diagnoses were depression and anxiety. Notably, after their diagnosis the frequency of psychiatric disorders increased both in people with MS and NMOSD. This suggests that after neurological diagnosis people with NMOSD may experience a significant psychiatric burden, especially depression.