Research Highlights From ECTRIMS-ACTRIMS 2023

We attended the 9th Joint European and American Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) meeting and have lots to share with you! The meeting took place on October 11-13 in Milan, Italy, bringing together over 8000 scientists, clinicians, and health care professionals from around the world to talk about the latest in multiple sclerosis (MS) research.  

This year, the scientific programme included 1,915 abstracts and 22 scientific sessions focused on various topics in MS research like Epstein-Barr virus, future therapeutics, biomarkers, and cognition, among others. Here’s some of the highlights from the conference. 

Multiple Sclerosis – Path to a Cure 

Dr. Stephen Hauser (University of California, San Francisco) delivered the opening address reflecting on the progress that’s been made in MS research. While there have been significant advances in the development of high-efficacy treatments for relapsing-remitting MS, Dr. Hauser noted the disease has not yet been halted. Data from clinical trials show that while disease activity is greatly reduced in terms of new lesions and relapses, there’s evidence for ‘progression independent of relapse activity’ or, PIRA. PIRA can occur at the earliest stages of MS and can continue throughout the course of the disease. This highlights the need for more effective therapies that can stop disease progression.  

Dr. Hauser believes we should be tackling MS at three different stages: 

1. Before symptoms start through prevention  

2. At the earliest stages of MS through early treatment 

3. The chronic disease stage with better therapies 

While we will need more tools and research to effectively address these stages, Dr. Hauser provided a hopeful message about the possibility that MS could be the first chronic autoimmune disease to be cured.

Epstein-Barr Virus and MS 

Epstein-Barr virus (EBV) has emerged as a strong risk factor for MS. EBV infects over 90% of adults and is the cause of infectious mononucleosis (commonly known as mono). MS occurs in only a small fraction of EBV-infected individuals. EBV is believed to be necessary, but not sufficient for the development of MS (learn more – here). 

• Dr. Thomas Berger (Medical University of Vienna) examined whether there are specific factors that protect a person against developing MS following EBV infection. Dr. Berger and team compared healthy controls and people with MS, who’ve been infected by EBV and had either high or low levels of EBNA1, a protein produced by EBV. They were able to identify virus and host specific factors (e.g., HLA-E genes which play a role in immune system function and other immune system factors) that may be associated with a 260-fold increase risk of MS. Further research is needed to understand these preventative factors that could one day help identify those at greatest risk of developing MS.

Emerging Therapeutics – Bruton’s Tyrosine Kinase Inhibitors (BTKi) 

There’s a need for therapies that can effectively reduce relapses while also addressing the chronic inflammation involved in progressive disease. One potential treatment in development targets Bruton’s tyrosine kinase (BTK), a key enzyme found in several immune cells linked to MS development and disease processes, such as B cells and myeloid cells. Several BTK inhibitors are in late-stage clinical trials and are being tested in people with relapsing MS, primary progressive MS, and non-relapsing secondary progressive MS (learn more about clinical trials – here). Some of the current BTK inhibitors in development are: 

• evobrutinib – Currently in phase 3 clinical trials for people with relapsing MS (Evolution trial). 

• tolebrutinib – Currently in phase 3 clinical trials for people with relapsing MS (GEMINI trial), primary progressive MS (PERSEUS trial), and non-relapsing secondary progressive MS (HERCULES trial). 

• fenebrutinib – Currently in phase 3 clinical trials for people with relapsing MS (FENhance 1 and 2 trials) and primary progressive MS (FENtrepid trial). 

• remibrutinib – Currently in phase 3 clinical trials for people with relapsing MS (REMODEL trial). 

Results from the phase 2 clinical trial for fenebrutinib was highlighted at the conference. In this study, they evaluated 106 people with relapsing MS taking either fenebrutinib or placebo (no active drug). They found that fenebrutinib reduced gadolinium-enhancing lesions by 90% and reduced new and enlarging T2 lesions by 95% in the brains of people with relapsing MS. The findings from this study are encouraging and indicate that fenebrutinib can enter the central nervous system and has potential to target MS disease activity. We are awaiting the results of the phase 3 clinical trials to understand the efficacy of all BTK inhibitors in treating active and non-active MS. 

Understanding the Earliest Signs and Symptoms of MS  

There’s emerging evidence that MS has a prodromal phase, an early set of signs and symptoms taking place before clinical MS symptoms and diagnosis. Understanding the earliest window when MS begins will enhance early detection and prevention of MS disease symptoms before they start (read more – here). 

• Dr. Ali Manouchehrinia (Karolinska Institute) examined if there were detectable sick leave patterns in the 10-year period before an MS diagnosis in a population in Sweden. By examining over 10,000 cases of MS and 50,000 healthy individuals, he found people living with MS showed a steady rise in sickness absence rates prior to MS onset compared to healthy individuals. Sickness absences peaked in the year prior to MS onset. More research is needed to understand the causes of these absences, providing more insight on the MS prodromal phase. 

Genetic link to disease progression in MS  

Did you know that over 200 genetic variants are linked to a higher risk of developing MS? Recently, an international research consortium found a new genetic variant (called rs10191329) that increases the risk of disability progression by almost 4 years as measured by shorter time to EDSS 6.0 (read more – here).  

• Dr. Christiane Gasperi (Technical University of Munich) presented findings from a study that investigated how genetic variant rs10191329 is associated with an increased risk of disease severity to further understand its role in disability progression. They examined over 1,000 people with relapsing MS in Germany and Sweden and found that rs10191329 was associated with brain atrophy, a marker of disease progression. This study supports earlier findings on this variant and helps us better understand how genetics can influence longer-term outcomes in MS.

Enhancing Well-Being  

Cognitive dysfunction, which is considered an invisible symptom of MS, can affect up to 70% of people living with progressive MS and can have a negative impact on relationships, employment, and daily activities (read more – here).  

• Dr. Anthony Feinstein (University of Toronto) presented the results from the MS Canada-funded international clinical trial that examined interventions to improve cognition in people with progressive MS. The trial called CogEx examined if cognitive rehabilitation, aerobic exercise, or a combination of both can improve cognition in people living with progressive MS. A total of 311 participants were given one of four interventions for 12 weeks:  

  • (1) cognitive rehabilitation and aerobic exercise  

  • (2) cognitive rehabilitation plus a sham exercise (i.e. light stretching and balance exercises) 

  • (3) aerobic exercise plus a sham cognitive task (i.e. internet training)  

  • (4) sham cognitive task (i.e. internet training) and sham exercise (i.e. light stretching and balance exercises) 

• Cognitive processing speed was measured using the Symbol Digit Modalities Test (SDMT). From this trial, they found that the combined interventions of aerobic exercise and cognitive rehabilitation were not better than either intervention provided alone, and these interventions were also not superior to the sham activities. Two-thirds of participants from all four intervention groups showed significant improvements in processing speed at 12 weeks, of which almost 50% retained these improvements at the 6-month follow up. The findings of this study show that cognition can be improved in people with progressive MS, which we didn’t know before (read more – here). More research is needed to understand the most effective approaches to improve cognitive function and to see who will best respond to these interventions. 

Biomarkers for MS 

Biomarkers are biological factors found in the body (e.g., brain, blood) that can help in the diagnosis and management of the disease. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are two emerging blood-based biomarkers that are being investigated for MS (read more here).  

• Dr. Elias Sotirchos (Johns Hopkins University) examined the biomarker NfL in over 7,000 people with MS over a three-year period. They found that those with higher levels of NfL at the start of the study showed a faster time to brain atrophy compared to those with normal levels of NfL. Those with persistently elevated NfL levels showed a 3-fold accelerated rate of brain atrophy compared to healthy controls and showed decreases in processing speed and walking speed. These findings show that NfL may be a useful biomarker for improved disease management. Further research will support the use of new biomarkers in routine clinical care.

Additional resources: 

Our highlights above only capture a few of the latest breakthroughs in MS research from the conference. If you’d like to learn more, you can check out all of the research abstracts published in the Multiple Sclerosis Journal.  

For research highlights from days one to three of ECTRIMS-ACTRIMS 2023, you can listen to The ECTRIMS Podcast.  

For an overview of key research topics covered at ECTRIMS-ACTRIMS 2023, listen to Jon Strum’s podcast RealTalkMS episode 320 on October 17, 2023 – ‘From ECTRIMS-ACTRIMS 2023 with Bonnie Higgins and Dr. Tim Coetzee.’