Research Highlights from ECTRIMS 2022

On October 26-28, 2022, the 38^th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) gathered scientists, clinicians, and health care professionals from around the world virtually and in-person in Amsterdam, the Netherlands. Over 8,700 delegates joined the conference from more than 100 countries. The scientific programme consisted of 1,700 abstracts and 200 speakers covering an array of cutting-edge research topics ranging from pediatric MS, progressive MS, treatments and prevention, pregnancy, COVID-19, and more. Here are some of the highlights from the conference.

Pediatric MS

Understanding demyelinating diseases and MS in children and adolescence

Dr. Brenda Banwell (Children’s Hospital of Philadelphia) delivered the keynote opening lecture with a summary of the last almost 20 years of research from the Canadian Pediatric Demyelinating Disease Program (CPDDP), supported by the MS Society of Canada, on understanding pediatric onset MS (POMS). Prior to the launch of CPDDP in 2004, the incidence and impact of pediatric MS in relation to MS in adults was not well understood. It is now well accepted that pediatric onset-MS occurs (1 in 100,000/year) and that MS is a “single disease across the age span”, meaning it shares the same risk factors (i.e., vitamin D insufficiency, second-hand smoking, Epstein Barr virus, obesity, genetics) and diagnostic criteria as the adult MS population. A key finding from this work demonstrated that children with MS typically do not accumulate physical disability until 10 years post-diagnosis, however changes in brain development are seen almost immediately. Within the first and second years following diagnosis, children with MS show an increase in the number of brain lesions and reductions in brain volume (brain atrophy). Additionally, they found reductions in thalamic volume associated with cognitive impairments, which affects one in three children with MS. Approximately 30-50% of children with MS experience depression and anxiety, emphasizing the importance of mental health in children with MS and their families. Dr. Banwell and team have provided significant insights into demyelinating diseases and the impact and trajectory of MS in children and adolescence.

Hear more from Dr. Banwell on The ECTRIMS Podcast – Episode 1: Day One Highlights of ECTRIMS 2022.

Progressive MS

Understanding the genetic link to MS disease severity and outcomes

Researchers have identified over 200 genetic variants associated with MS disease susceptibility; however, little is known regarding genes associated with MS disease severity and outcomes. Dr. Adil Harroud (McGill University) presented new findings from the International Multiple Sclerosis Genetics Consortium (IMSGC) that assessed sequencing data from 12,584 people with MS, leading to the identification of two new genetic variants called rs10191329 and rs149097133, preferentially found in the central nervous system (CNS). In a subpopulation of 8,325 people with MS, those with the rs10191329 and rs149097133 variants showed faster disability worsening and a shorter time in reaching expanded disability status scale (EDSS) 6.0 (requiring use of a walking aid) than those without these variants. They also found that rs10191329 was associated with a nearly two-fold higher rate of demyelination and greater lesion count. Dr. Adil Harroud and team estimate 12.8% of the variability seen in MS disease severity may be attributed to genetics. These findings will help to develop new drug candidates that better target genetic variants associated with disease severity (abstract link – here).

Latest in MS Treatments and Prevention

Preventing MS symptom onset in people with radiologically isolated syndrome with early intervention

Radiologically isolated syndrome (RIS) is a preclinical phase of MS in which people show early detectable MS-like lesions on the brain or spinal cord by magnetic resonance imaging (MRI), but do not have MS symptoms. Dr. Darin Okuda (University of Texas Southwestern Medical Center) presented findings from the ARISE study that evaluated the impact of early intervention in people with RIS to determine whether they could prevent or delay the onset of MS symptoms. They conducted a multi-center, randomized, double-blinded clinical trial across 12 centres in the US using dimethyl fumarate (DMF) as the therapeutic intervention in people with RIS (read more on clinical trials). A total of 87 people with RIS were randomized to receive either 240 mg of DMF or placebo (no treatment), twice daily for 96 weeks. The clinical trial showed that treatment with DMF resulted in an over 80% risk reduction of the first clinical demyelinating event in comparison to the placebo group. People with RIS receiving DMF also showed reductions in the number of new or newly enlarging lesions on MRI. DMF was well tolerated in people with RIS, with more moderate adverse events reported in the DMF treated group than the placebo group however, severe adverse events were comparable between the DMF and placebo groups. This study is the first to show a risk reduction with treatment of DMF in people with RIS, and supports the benefit of early intervention in MS disease course (abstract link – here).

Vitamin D supplementation in the prevention or delay of MS disease activity

Vitamin D insufficiency is a known risk factor of MS. Two clinical trials investigated whether vitamin D supplementation can prevent or reduce MS disease outcomes. The first trial, an Australia-New Zealand study (PREVANZ) led by Dr. Helmut Butzkueven (Monash University), assessed whether vitamin D supplementation in people with clinically isolated syndrome (CIS), who are at a high risk of developing MS, could prevent or delay the development of relapsing-remitting MS (RRMS). A total of 204 study participants with CIS received different doses of vitamin D (1,000, 5,000, and 10,000 IUD) and were compared to placebo (no vitamin D). After 48 weeks of supplementation, they found no difference in the onset of definite MS through vitamin D supplementation, indicating that vitamin D is not an effective treatment to prevent development of RRMS in the CIS population (abstract link – here).

A second clinical trial led by Dr. Ellen Mowry (John Hopkins University), looked at whether vitamin D could reduce disease activity in people with RRMS. Participants with RRMS who were taking glatiramer acetate were provided an add-on therapy of high (5,000 IUD) vs low (600 IUD) dose of vitamin D over 96 weeks. They found that a high dose of vitamin D supplementation did not reduce disease activity in people with RRMS, including no statistically significant differences in relapses or other MRI outcomes (abstract link – here). These findings suggest that vitamin D as an add-on therapy did not reduce disease activity in people with RRMS.

Pregnancy and MS

Understanding pregnancy outcomes for anti-CD20 therapy in MS

Dr. Celia Oreja-Guevara (University Hospital San Carlos) presented new findings from a study examining pregnancy outcomes in women with MS treated with the anti-CD20 ocrelizumab. The researchers identified a total of 2,020 pregnancies among women with MS treated with ocrelizumab from a large database. Most of the pregnancies resulted in live births (79%) and of these 57.1% were full term (after 37 weeks) and 10% were pre-term (before 37 weeks). The proportion of live, full-term, and pre-term births were comparable between those treated and not treated with ocrelizumab. The findings from this large dataset suggest that ocrelizumab exposure does not increase the risk of preterm birth or other adverse outcomes during pregnancy, which is consistent with previous findings from epidemiological data (link to abstract – here). Pregnancy outcomes in women taking anti-CD20 DMTs will continue to be assessed.

COVID-19 and MS

COVID-19 vaccination in people with MS

Two years after the pandemic, researchers discussed the data collected globally regarding COVID-19 in people with MS. Overall, vaccination significantly decreased the risk of severe outcomes for people living with MS. Dr. Anat Achiron (Tel-Aviv University) shared her findings that people with MS taking ocrelizumab (anti-CD20 therapy) or fingolimod (sphingosine 1 phosphate receptor modulator therapy), had a reduced immune response post-vaccination, while the immune response of those untreated or on other DMTs were at normal levels. Dr. Nikos Evangelou (University of Nottingham) shared population-level data indicating that ocrelizumab and fingolimod were associated with higher rates of COVID-19 infection post-vaccination, compared to the general population as well as greater COVID-19 related hospitalization and mortality, compared to other DMTs (link to abstract – here). These findings suggest that people with MS on these specific DMTs may be more vulnerable to COVID-19 infection, despite being vaccinated. It is important that people with MS consult their healthcare team to maximize the effectiveness of their vaccinations and discuss other prevention measures.

Additional resources:

This article only captures a few of the latest breakthroughs in MS research presented at ECTRIMS 2022. All research abstracts have been published in the Multiple Sclerosis Journal.

For research highlights from days one to three of ECTRIMS 2022, listen to The ECTRIMS Podcast by Brett Drummond.

For an overview of key research topics covered at ECTRIMS 2022, listen to Jon Strum’s podcast RealTalkMS episode 270 on November 1, 2022 – ‘From the 2022 ECTRIMS Congress with Dr. Bruce Bebo.’