ECTRIMS 2024: expectations?

Will any advances in the symptomatic management of MS improve clinical outcomes and quality of life of people with MS?

Sep 17, 2024

I landed in Copenhagen for the ECTRIMS jamboree yesterday morning. I have several meetings before ECTRIMS starts on Wednesday. Yes, ECTRIMS is a meeting of meetings. I am attending several trial steering committee meetings, industry-led advisory boards to discuss future MS trials, and investigator meetings of a few current MS trials. I will also meet with many other MS stakeholders, friends, and colleagues to discuss all things MS.

Neurology and MS conferences are often criticised for being marketing jamborees where big pharma brainwashes unsuspecting neurologists into prescribing their wares. However, the days of excess and unabashed marketing are gone. Most people attending these conferences are self-funding, or at least partially self-funding, and are here to learn, present their research, and exchange ideas. The in-person meetings and serendipitous encounters count more. I learnt how important these were during the pandemic. There are no substitutes for real-time face-to-face encounters to exchange ideas.

Please be aware that numerous restrictions at the national and EU levels prohibit big pharma companies from bribing HCPs to prescribe their products, so it is not worth taking the risk. You have to look at the recent fines handed down to some MS companies in the US for this behaviour to realise that it is not worth it and the reputational damage is crippling. That doesn’t mean there is less marketing, and I suspect the Exhibitor Hall and Stands will be as glamorous and over the top as in previous years.

In addition to my speaking activities (see below), I will be involved with launching the new or second edition of the ‘MS Brain Health: Time Matters’ policy document and volume 1 of the MS-Seflie self-management guide for people with multiple sclerosis.

This ECTRIMS promises to be a big one with the release of the New McDonald Diagnostic criteria, and the late-breaking session will see the results of three phase 3 trials being presented, i.e. the STAT-2 or high-dose simvastatin in secondary progressive MS trial and the relapsing MS and non-relapsing SPMS tolebrutinib studies.

I will scour the programme to see if any significant MS challenges have been solved. The following is a short list of some of the challenges I am particularly interested in.

Presymptomatic MS challenge

How does infectious mononucleosis trigger MS? If it is due to molecular mimicry, why is there such a long lag time between viral exposure and the onset of MS? If it is due to dysregulated immune function, why don’t we see MS exacerbations or worsening post-AHSCT, as AHSCT is a treatment that is associated with EBV reactivation in over 80% of pwMS who undergo the procedure? If MS is due to ongoing EBV latent-lytic cycling, why is it so difficult to find the virus?
Will vitamin supplementation at a population level decrease the incidence (new cases) of MS? Or are low vitamin D levels in people at risk of MS reverse causation and the presymptomatic phase of MS associated with a consumptive hypovitaminosis? Almost all inflammatory diseases, whether subclinical or overt, are associated with low vD levels.
How does lung inflammation due to smoking, solvent and air pollution exposure contribute to an increased risk of getting MS? What are the mechanisms involved? Is the requirement for lung or systemic inflammation, for example, obesity-associated inflammation, a requirement to develop MS?
How does childhood and adolescent obesity increase the risk of getting MS? Is this simply an association and the actual driver is environmental, i.e. something in the diet that contributes to the risk of getting MS and obesity? For example, the increasing incidence of MS and other autoimmune diseases during modern times seems to parallel the increasing consumption of processed sugar.
Why don’t all family members of people with MS who have lesions on MRI that look like MS, i.e. have radiologically isolated syndromes, develop MS? Similarly, why do so many people with undiagnosed MS at post-mortem not get diagnosed in life? Do they cure themselves of the disease before the first clinical event?

Symptomatic MS challenges

Why is the incidence of MS increasing globally, particularly amongst young women with an increasing sex ratio? In the early 1900s, the ratio of women to men with MS was close to 1:1. In some countries, this ratio has increased to above 3:1. At the same time, the incidence of primary progressive MS seems stable with a sex ratio of close to 1:1.
The latitudinal gradient of MS incidence is decreasing in many countries, such as Norway and the USA. What has changed in the environment to reduce this gradient? Is a change in diet? The ubiquitous use of sunblock to prevent skin cancer is now causing low vD levels in areas close to the equator.
How do immune reconstitution therapies work? Are they doing more than simply rebooting the immune system? Are they working as immune system rejuvenation therapies and resetting antiviral immune responses? Are they working as anti-EBV immunotherapies?
Is there an acceptable definition of an MS cure that the MS community can get behind? How many people with MS treated with IRTs and in long-term remission are cured?
From the recent press release, it is clear that tolebrutinib, a new generation BTK inhibitor, dissociates the effects of relapse and disability worsening in relapsing MS and probably progressive MS. Will this observation extend to biomarkers of end-organ damage such as brain volume loss and slow expanding lesions? Will the MS community accept that relapse and MRI activity are not the real MS, and will the focus shift to processes?
The human brain processes information in a way that leads to errors or cognitive biases. When will MS healthcare professionals (HCPs) learn to train their brains to think differently to avoid the biases that affect how they manage their patients with MS? How can we learn from the social sciences to suppress medical gaslighting? This will help people with MS to get diagnosed and treated earlier and their symptoms documented.
What is it about female physiology that impacts on MS disease course? Why are we not hacking this to treat MS?
Is peri and post-menopausal HRT disease-modifying? If yes, as the evidence indicates, why aren't MS HCPs making sure all women with MS who are post-menopausal are on HRT?
Why are we not treating MS with new therapeutic strategies, e.g., using safer induction-maintenance protocols? These are well-developed concepts in other disease areas, so why are we so slow to adopt them?
Will any advances in the symptomatic management of MS improve clinical outcomes and quality of life of people with MS? Is there any data to support the marginal gains philosophy of managing MS, i.e. managing MS holistically?

I would like to know if there are any research areas you would like to hear about. Next week, I will write a more detailed newsletter summarising the highlights of the meeting and what they mean for people with MS.

My presentations

The following is the list of my official presentations at the conference. I will record some of these talks for you.

How to define treatment failure in progressive MS
Gavin Giovannoni (United Kingdom)
Wednesday, 18 September 202409:05 - 09:20 CEST

Is your patient's cognitive decline ageing or MS related?
Gavin Giovannoni (United Kingdom)
Thursday, 19 September 202411:00 - 11:10 CEST

Safety and Efficacy of Frexalimab in the Treatment of Relapsing Multiple Sclerosis: 18-month Results from the Phase 2 Open-Label Extension
Gavin Giovannoni (United Kingdom)
Thursday, 19 September 202412:11 - 12:18 CEST

Experience with patient-reported outcomes in clinical practice
Gavin Giovannoni (United Kingdom)
Thursday, 19 September 202414:50 - 15:05 CEST

Equitable access and patient-centred treatment in multiple sclerosis: Expert insights
Mitzi Joi Williams (United States) / Tania Pilz (Belgium) / Victoria Reese (United States) / Gavin Giovannoni (United Kingdom)
Friday, 20 September 202412:00 - 12:30 CEST

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General Disclaimer

Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Queen Mary University of London or Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have problems, please tell your healthcare professional, who will be able to help you.