ECTRIMS2024 – ECTRIMS Patient Community Day – Ask the Expert

Q1: If the research on the brain-gut connection is promising, why should we not consider a faecal transplant to optimise or improve our gut health if that is part of the issue? Surely, if it proved effective, it would be more economical than these expensive therapies.

The gut microbiome is an interesting avenue of MS research at the moment. Studies have shown that there appear to be differences between the gut microbiome of people living with MS compared to healthy controls. However, there is still a lot that we don’t know about this topic, including what exactly ‘a healthy gut microbiome’ is. There have been some small early trials that have looked at faecal transplants as a treatment approach in multiple sclerosis with some success. As our understanding of this area in general increases, it will likely lead to this approach being refined in larger trials and this will give us a better idea about whether it may be an effective strategy for some individuals.

Q2: Why isn’t hematopoietic stem cell transplantation (HSCT) more widely available as a standard treatment for MS, considering it is not an experimental procedure? I underwent HSCT in 2022 and have been relapse and disease-modifying therapy (DMT) free since, yet I had to travel abroad to access this treatment, despite it being performed in my home country for other conditions. Additionally, is HSCT considered a long-lasting solution for MS patients?

HSCT is a treatment approach that works by essentially ‘rebooting’ the immune system of a person living with MS. Many clinical trials have been performed to assess the benefits of HSCT for people living with MS. The results of these trials have shown that HSCT can be a very effective therapy for some people living with MS, where the procedure can provide long-term suppression of the disease. Overall, it is thought that people who are early in their disease course, have high levels of inflammation and have failed on existing therapies are most likely to receive benefits from HSCT. Although the safety profile of HSCT has improved over recent years, there are still a number of risks associated with it, which has meant that it is not used as extensively as other treatment approaches.

Q3: Can you provide information on Tolebrutinib and its potential effects on secondary progressive multiple sclerosis (SPMS)? What is the current evidence regarding the effectiveness of Tolebrutinib for treating SPMS? As someone with SPMS, I’m also interested in learning about other treatment options besides exercise, as I currently engage in chair dancing, yoga, gym workouts, and weekly physiotherapy. Lastly, are there any insights or treatments available for reducing the speed of disability progression in SPMS and managing chronic pain associated with this condition?

At ECTRIMS 2024, the results of the HERCULES clinical trial were presented. HERCULES was a trial that was testing the effectiveness of a new drug called Tolebrutinib to reduce disease progression in people living with non-relapsing secondary progressive MS (SPMS). Excitingly, the results of this trial were positive, and it was found that Tolebrutinib significantly reduced disability progression compared to placebo. An important part to note about this trial is the fact that the participants had non-relapsing SPMS. This suggests that Tolebrutinib is not targeting the inflammatory component of the disease, which all existing therapies act against, but rather the neurodegenerative component. This is a critical area of unmet need in MS, so further work will be done now to truly understand exactly how Tolebrutinib is working to reduce disease progression in MS.

According to the press release from Sanofi, the company behind the trial, “study results will form the basis for future discussions with global regulatory authorities with submissions starting in H2 2024. Tolebrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority”.

Q4: Can you discuss the role of Bruton’s tyrosine kinase (BTK) inhibitors in the treatment of relapsing MS, including their effects and whether they represent the most promising advancements in medication for this condition?

At ECTRIMS 2024, the results of a clinical trial of a Bruton’s tyrosine kinase inhibitor (BTKi) called Tolebrutinib in people living with relapsing-remitting MS were presented. This trial was called GEMINI. Unfortunately, this trial failed to meet its primary endpoint, which was to reduce annual relapse rates when compared to an existing MS medication called Teriflunomide. However, some of the results of the secondary measures that were investigated – such as disability progression – were positive. When combined with the results of the HERCULES trial, it may mean that we continue to see this treatment investigated as a potential therapeutic option in relapsing-remitting MS (despite having failed this trial).

Q5: Has the role of Vitamin D been implemented in clinical practice, and what are the updated recommendations for vitamin D supplements for MS patients? Additionally, are these recommendations different for patients with RRMS, SPMS, and PPMS?

At this stage, the key factor that is taken into account is ensuring that people living with MS (regardless of whether it is RRMS, SPMS and PPMS) are not Vitamin D deficient.

An interesting presentation was given at ECTRIMS 2024 regarding the results of the D-LAY MS clinical trial. In this trial, it was found that supplementation with high-dose Vitamin D could be effective at reducing disease activity in the early stages of multiple sclerosis. In particular, they found that it had the potential to reduce the risk of conversion from Clinically Isolated Syndrome (CIS) to MS. As the treatment was safe and well tolerated, it was suggested that it might be beneficial to use in addition to an existing therapy. It is important to note that other clinical trials have found different results to this, though this could be because they were using different outcomes measures. This result needs to be validated further before it is adopted into clinical practice.

Q1: With the climate crisis affecting those of us with MS and other conditions that worsen in extreme heat, what measures would be recommended? I’m a biomedicine student, and wearing a lab coat is particularly uncomfortable.

This is an important question, but one that it is difficult to give a definitive answer to. I would recommend discussing this issue with your neurologist, your MS nurse (if you have access to one) and your employer. It has been shown that factors such as access to appropriate air conditioning or drinking ice cold water instead of tap water can help lessen the impacts of overheating in people living with MS. The actual strategies that a person implements is up to the individual based on what they can do in the situation and what they find to be effective for them.

Q2: Does anyone have any knowledge of a sore, prickly throat constriction associated with MS? This occurs sporadically and occasionally.

Difficulty swallowing or dysphagia can be a symptom experienced by people living with multiple sclerosis. It is important that you discuss any symptom that you are concerned about with your healthcare professional, as there may be ways that they can help manage it.

Q3: How would you measure changes in cognition to understand them as a sign of MS progression? What are the most common cognitive changes?

There are several tests that are used to assess cognitive changes in people living with MS. The different tests measure different aspects of cognitive function. There are several cognitive changes that can occur in people living with MS, including decreases in processing speed, as well as issues with memory and attention.

Q4: Are there any new insights regarding the treatment of fatigue?

The biggest development in the treatment of fatigue for people living with MS is that there is an increased understanding that fatigue can be multi-factorial. There is a growing awareness that it is important to determine what is contributing to fatigue and whether these can be addressed. As an example, it is known that people living with MS have worse quality sleep than the general population and that this leads to an overall feeling of fatigue. While this may seem relatively straightforward, it is important because poor sleep quality can be addressed through different lifestyle strategies and/or pharmaceutical intervention. Similarly, it is also known that people living with MS are at a higher risk of experiencing depression. One of the symptoms of depression is an increased feeling of tiredness or fatigue. Depression can also be treated through the support of a psychologist and/or appropriate medications.

Q1: I am a father of two children and have been living with MS for over 20 years. What are the recommendations for staying vigilant with my children’s health? Should testing for EBV (Epstein-Barr Virus) be considered? Are there any other points to keep in mind?

Should family members (siblings, children, parents) of individuals with MS undergo brain MRIs to detect RIS at an early stage?

These are important questions, as we know that one of the key concerns of parents living with MS is whether their children are also at risk of developing the disease. Research has shown that there are both genetic and environmental factors that can increase the risk of developing MS. However, our understanding of how these factors interact is still limited. This makes it virtually impossible to get any sort of prediction of the likelihood of an individual to develop MS. While it may change as our knowledge of this improves, there is no suggestion at the moment that family members of a person living with MS should undergo any special or regular testing to assess their risk.

Q2: Is testing for EBV strains widely available? Can a blood test determine which strain of EBV a person has had in the past, to better understand the risk factors for family members of people with MS?

My adult daughter has had Glandular Fever, Chickenpox, and Shingles, so she definitely carries EBV in her body. I have late-onset Primary Progressive Multiple Sclerosis (PPMS). My consultant has advised that she takes Vitamin D. I, too, had all of these illnesses in my younger years and am worried that she may be at high risk.

There are relatively simple tests that can be performed to detect whether a person has been previously exposed to EBV. However, it is important to note, that it is a very common virus and over 90% of the world’s population has been infected by it at some point in their lives. While EBV is the virus that causes glandular fever or infectious mononucleosis, most people that are infected do not develop any symptoms and so are never aware of it. This tells us that a very large percentage of people who tested for previous exposure to the virus would return a positive result. However, it also tells us that most people that have been infected with EBV do not develop MS. Considering this, testing for EBV to assess risk of developing MS is not something that is part of routine clinical practice at this time.

Q3: For those of us with MS, vaccinations come too late. If one is developed one day, that would be fantastic. However, for those of us currently living with MS, why can’t we have antiviral treatments to eliminate and control EBV, which we cannot naturally clear from our systems?

Should all patients be taking antivirals for EBV, rather than waiting years for clinical trials to conclude?

What is the current status of developing a vaccine for mononucleosis?

With our current understanding of the role that EBV may play in the development of MS that a vaccine against this virus could potentially prevent the disease from occurring. Early-stage trials are currently underway to test an mRNA vaccine against EBV, though it will take some time to know if this is safe and effective, as well as if it has any impact on MS.

As well as showing that EBV may be critical for the disease to start, there is also some evidence from research that the virus could also be important in driving disease progression. For this reason, studies are investigating the use of anti-virals as a potential novel treatment approach in MS. As with all new therapeutics, it is important they go through the appropriate studies and clinical trial phases to truly understand both their safety and effectiveness before they are used outside of this setting.

Q4: Does having a high weight have any connection to MS? Is there any link?

Yes, it has been shown that having a high body-mass index (BMI) increases the risk of developing MS and leads to greater disease severity and worse outcomes. BMI is an indirect way of estimating the amount of body fat that an individual has, so these results have suggested that maintaining a healthy weight is an important part of managing MS.

Q1: With the advice for exercise, how do we advocate for access to gyms, accessible machines, and similar facilities? There seems to be a significant amount of individual advice (e.g., “exercise!”), yet very little practical support for many people to actually do so.

Is a walking distance of 5 km or more suitable for those who have recently been diagnosed with MS?

As a person with SPMS, using a rollator and experiencing foot drop, walking as exercise is not feasible. Wheelchair-based exercise is the only option available. Does anyone have similar experiences?

These questions raise good points regarding exercise for people living with MS. Firstly, studies have shown that exercise is an important part of any MS management plan for several reasons. Exercise is an important way of maintaining a healthy weight, which research has shown can reduce disease progression, can help with symptom management and is critical for lessening the risk of other comorbidities that people living with MS are susceptible to.

In terms of the type of exercise, the messaging is always focused on finding an activity that is accessible, achievable, something that can be maintained and provides benefits for the individual. Some guidelines have been published in the MS Journal, specifically focused on exercise for people living with MS, which have been shared by several MS Societies around the world. As well as this, a new important message that has been discussed at ECTRIMS is ‘prehabilitation is better than rehabilitation’, which essentially means that the earlier a person living with MS can start an effective exercise routine after diagnosis, the better their long-term outcomes will be.

Q2: What are the solutions for those who know they need better-quality food but can’t afford it? Many of the recommendations are nearly impossible for those on a limited income.

This is an important topic. There has been a lot of focus over recent years on the social determinants of health and income, as part of socio-economic status, has been part of this. Although more evidence is needed, studies have shown that a lower socio-economic status is associated with both an increased risk of developing MS and worse disease outcomes. One of the risk factors that is known to be associated with this is obesity, which is linked to diet quality. There was significant discussion at ECTRIMS 2024, especially in the nurses session, regarding the importance of understanding the financial situation of people living with MS and keeping this in mind when having conversations about ways of managing the disease. You can hear more about this in the ECTRIMS podcast in our MS Nurses at ECTRIMS 2024 episode.

Q3: What other factors, tests, or vitamins should a patient monitor for better treatment?

The important part around this is that a person living with MS should try and live an overall healthy lifestyle. This includes having a balanced diet, regular exercise, not smoking, maintaining social circles and seeking support to address any mental health concerns.

Q4: During my recovery from SPMS disabilities, my diet for two years consisted of two raw eggs and a stick of butter blended together every morning for breakfast, with no sugar or sugar substitutes. I have heard of other MS patients being advised to avoid sugar, but have any other MS patients been recommended to include two raw eggs and a stick of butter for breakfast as a means to help repair damaged myelin?

What are the most recent findings on the impact of diet on MS symptoms and flare-ups? I often encounter differing opinions on this subject.

Research has shown that diet can be an effective lifestyle modification to help manage MS. Although many studies have looked at different sorts of ‘MS diets’, there is no evidence at this stage to suggest that any one diet provides superior benefits. Currently, the best advice for people living with MS is to follow a healthy, balanced diet.

Unfortunately, there is no published evidence to suggest that a diet of raw eggs and butter can stimulate myelin repair in people living with MS. In terms of diet and remyelination, there has been research in animal models that has found that intermittent fasting can have a positive impact on myelin repair. This finding was replicated with the use of a diabetes drug called Metformin, which mimics the process of fasting. Metformin is currently being tested in a clinical trial, called CCMR Two, at the University of Cambridge. Results of this trial are expected around the time of ECTRIMS 2025.

Q1: Could you please provide a straightforward explanation of the recent changes to the McDonald diagnostic criteria? In the past, we have described it as lesions disseminated in time and space. What would be an effective way to explain this to someone awaiting diagnosis?

The complete revised McDonald Criteria for the diagnosis of MS are not yet published. While there have been hints about some of the changes that have been made, only the committee that were responsible for making the revisions are aware of the full, finalised criteria. However, it should be said that there has been a lot of discussion about how these criteria will be communicated, both to neurologists and the public, once they are available. Stay tuned to the ECTRIMS website and your local MS society website, as they will definitely provide easy to understand information once it is available.

Q2: I wonder how much is currently known about the subtypes and atypical presentations of MS. Are we likely to see new types being officially recognised in diagnostic manuals? Additionally, could you discuss misdiagnosis? My partner was misdiagnosed for a decade with chronic fatigue syndrome (CFS). How common is this, and what measures can be taken to prevent it? I assume that women are particularly at risk of such issues.

Like MS, NMOSD and MOGAD are autoimmune diseases that cause damage to myelin. While they have some factors in common, each disease has unique aspects that must be properly understood. To manage each condition effectively, accurate diagnosis and treatment is important. Considering this, ECTRIMS has placed a large focus on ensuring that these disorders are also covered during the conference. At ECTRIMS 2024, NMOSD and MOGAD (as well as paediatric MS and autoimmune encephalitis) were discussed on Pre-Day – an additional day at the beginning of the conference specifically devoted to these rare conditions.

Q1: Is paediatric MS also treated to optimise Vitamin D levels?

There are no clear guidelines for the clinical use of vitamin D as a specific treatment for paediatric MS. Similarly to adult-onset MS, children living with MS may be advised to use Vitamin D supplements if they are deficient.

Q1: How should paediatric MOGAD be treated if immunoglobulins are not tolerated by the patient? For MOGAD, what is the best approach for patients presenting with increasing symptoms consistent with transverse myelitis, such as progressive loss of sensation, but with an MRI that does not show lesions or demyelination? Are there additional tests that could help confirm a MOGAD attack? What other potential causes would you investigate? If no alternative causes are identified, would you proceed with the standard MOGAD treatment options?

These clinical questions would always be addressed on an individual basis, as there are many factors that would come into that decision making process.

Q2: What does “sero-negative” mean?

People living with NMOSD usually have antibodies that target a protein called aquaporin-4. Sero-negative refers to people that meet the clinical criteria for NMOSD, but don’t have these antibodies in their blood.

Q3: Is physiotherapy important for MOGAD?

It is known that MOGAD can cause symptoms including stiffness, paralysis and muscle weakness. These symptoms have all been shown to respond to physical therapy, which can help provide rehabilitation following attacks.

Q1: How is the pressure on the healthcare system impacting treatment possibilities on a global level? I have been told ‘we are low on staff’ more than once…

This is a difficult question to answer, as there is little data available. What we would say is that we know that neurologists, MS nurses and other allied health professionals around the world are committed to trying to provide the best quality of care for people living with MS. It is why our theme for ECTRIMS 2024 was ‘dedicated to the dedicated’. In saying this, we recognise that there are definitely barriers that exist that can prevent this from happening sometimes, which is why we have also placed a focus at the congress of discussing diversity and equity – essentially to ensure that we are discussing important matters to try and achieve the best outcomes for all people living with MS around the world.

Q2: When the most effective DMTs are not slowing the progression of the disease, what then?

This is a great question. One of the most important developments in the treatment of MS is the large number of options that are now available. This is critical, as we know that some people will not respond to certain treatments, or the treatment effectiveness will lessen over time.  If this occurs, having multiple options means that these individuals can switch to another highly effective therapy in order to try and stop or slow disease progression. In instances where multiple highly effective therapies have failed, individuals might be considered for a treatment such as HSCT. This is also why it is important to continue to develop new treatments, so that we have as many different choices for people living with MS as possible.

Q3: Do you also join forces on the research?

Definitely! Collaboration is an important part of MS research and a key to helping make progress as quickly as possible. This is another reason why congresses, such as ECTRIMS, are so important. These meetings are a great opportunity for researchers from around the world to hear about the latest findings, discuss ideas and form new collaborative partnerships.

Q4: Are there any of you who have been definitively cured?

At this stage, there is no suggestion that any person has been cured of multiple sclerosis. As the exact cause of MS is still unknown, it is very difficult to think about a ‘cure’. However, there are some treatments that have shown to provide very effective long-term remission of the disease. In these instances, it is often said that the person has ‘No Evidence of Disease Activity’ or NEDA, but they are not cured.

Q5: Is it now believed that there is an underlying process to MS—smouldering MS—that represents the true nature of the condition?

Smouldering MS is a name given to a process known as PIRA, which stands for Progression Independent of Relapse Activity. Essentially, there are two main factors that drive disease in MS – inflammation and degeneration. Historically, it had been thought that relapsing-remitting MS was all about inflammation and that shifted to degeneration when a person developed secondary-progressive MS. Our understanding of this has changed significantly in recent years and we now know that this degeneration process is happening from the very earliest stages of disease. Both parts are important, but all the existing therapies really target the inflammatory component of the disease. Considering this, there is now a real focus on developing treatments that can also target this underlying degenerative process.

Q6: Could it be important for health professionals to recommend that people with MS visit the MS Society? There, support is available for people with MS and their families, including rehabilitation, psychological services, and social work assistance.

It is important that people living with MS have access to high-quality, trustworthy sources of information and support. MS organisations around the world are often a very good starting point for this, as they can either help directly or be able to provide information regarding other resources.

Q7: Is MS on the rise? If so, why do you think this is, or are we simply better at diagnosing it now?

Recent studies have indicated that the prevalence of MS is increasing. While we don’t know exactly the reasons for this, improved ability to diagnose may be part of the explanation. The other possibilities that have been suggested are that it is related to an increase in known risk factors for developing MS. As an example of this, it is known that obesity increases the risk of a person developing MS and obesity rates around the world are higher now than in the past.

Q8: Should a person with SPMS discontinue DMTs after reaching a certain age? Are there any age-related limitations to treatment? For instance, would it be beneficial for individuals over 60 years old?

There are a few important points to discuss around this concept. Firstly, in terms of the treatment of SPMS, studies have shown that existing treatments (even those approved for RRMS) can provide benefits if there is still an inflammatory component to the disease – that is, the person is still experiencing relapses.

In terms of the question regarding whether treatment is effective in older individuals, one of the key issues is that there isn’t a lot of data for people in this age group. Indeed, this was one of the topics covered in the Patient Community Day topic of ‘Diversity’, regarding the need to include older people in clinical trials, as opposed to them being excluded as they have in the past. However, the use of large clinical databases that included significant amounts of real-world observational data has helped start to answer some of these questions. Recent research has suggested that discontinuing therapies in older individuals who have had stable disease for several years may be an option, however, it would likely increase the risk of future disease activities. As always, these decisions will be made on a case-by-case basis and require several factors to be taken into account during discussions between the person living with MS and their neurologist.

Q9: What is the relationship between menopause and MS in women, particularly regarding symptom management and disease progression? Specifically, can menopause lead to a cessation of MS symptoms, and what evidence exists about the impact of hormonal changes during menopause on MS? Additionally, how can women differentiate between MS flare-ups and menopause-related symptoms, and what strategies can be employed to alleviate overlapping symptoms? Given the significant number of women affected by MS, how can we better inform middle-aged women about recognizing these symptoms? Finally, are there any studies investigating the effects of hormones, including the use of oral contraceptives, on MS symptoms, and how might peri-menopause and menopause influence disease progression compared to men?

All of these are fantastic questions focused on a hot topic in MS research at the moment, which is the impact of menopause on women living with MS. Firstly, we know that the disease doesn’t stop when a woman enters menopause. However, the data on exactly what happens during this time is not conclusive. Considering this, more studies are needed to improve our understanding of disease progression and symptom worsening before, during and after menopause. One symptom that has been of particular interest is cognition, as there is a strong suggestion that this worsens after a woman living with MS experiences menopause.

Hormone replacement therapy (HRT) has been discussed as a therapeutic option for women living with MS once they reach menopausal age, though there is no clear evidence yet for the benefits that this may generate. Although there is no suggestion that HRT would work differently in woman living with MS, there has not been enough studies to truly determine whether it would have a significant impact on disease progression or help with symptom management.